1985 |
Kaufman, Paul Leon |
F06Activity Code Description: Undocumented code - click on the grant title for more information. |
Iatrogenic Changes in Trabecular Meshwork/Ciliary Body @ University of Wisconsin Madison |
1 |
1985 — 2009 |
Kaufman, Paul Leon |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Anterior Ocular Segment Physiology and Pharmacology @ University of Wisconsin Madison
DESCRIPTION (provided by applicant): This project will characterize: functional/structural responses of the monkey aqueous human formation/drainage apparatus to pharmacologic probes; pathophysiology of deviations from normal function/structure produced by long-term antiglaucoma drug treatment; the role of cholinergic/adrenergic innervation in normal function, structure, their responses to pharmacologic agents, and deviations from normal produced by long-term antiglaucoma drug treatment; cytoskeletal, cell junctional, and extracellular matrix interactions of human trabecular meshwork and ciliary muscle cells to pharmacologic and biologic probes; the effect on aqueous outflow of relevant proteins encoded by genes delivered to the anterior chamber. Aqueous formation and drainage will be determined by perfusion and fluorophotometry. Accommodation will be stimulated by cholinergic agonists or a midbrain electrode and determined by coincidence refractometry. The ciliary muscle will be disinserted to identify primary drug effects on the trabecular meshwork. Parasympathetic denervation will be induced by ciliary ganglionectomy or panretinal photocoagulation, sympathetic denervation by superior cervical ganglionectomy. The effects of cholinergics, adrenergics, cyclic nucleotides, G-protein activators, hormones, peptides, prostaglandins, cytoskeletal agents, calcium channel blockers, cannabinoids, ionophores, carbonic anhydrase inhibitors, corticosteroids, and other compounds will be assessed in previously untouched, autonomically denervated, ciliary muscle disinserted, and long-term antiglaucoma drug-treated eyes. Agonists, antagonists, mediators, metabolites, and protein and RNA synthesis inhibitors will be used, and interactions among drug classes sought. Aqueous formation and drainage will be evaluated after injection of vectors containing genes whose products may affect aqueous humor dynamics. In vitro responses of trabecular meshwork and ciliary muscle cells to pharmacologic and biologic probes will be studied using immunohistochemistry to examine cytoskeletal and cell junctional changes. Structural parameters in the meshwork and ciliary muscle/processes of intact eyes will be evaluated by light/electron microscopy, immunohistochemistry and quantitative morphometry.
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1 |
1985 — 1986 |
Kaufman, Paul Leon |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Natural History of Angle Closure Glaucoma Suspects @ University of Wisconsin Madison
Primary angle closure glaucoma is a significant cause of visual loss and blindness. Appropriate therapy, however, when administered in time is highly effective in curing the disease and preventing loss of vision. It is also a disease that usually occurs acutely with little or no previous warning. Research to data has done little to provide indicators that might accurately identify eyes at risk so that appropriate treatment could be instituted prior to the onset of an acute (potentially blinding) attack. Recognizing these facts, the National Advisory Eye Council Vision Research Program Planning Committee indicated an urgent need for the study of early detection and treatment of angle closure glaucoma patients. The present project is designed as a two center coordinated study to determine the natural history of angle closure suspect patients. These patients will be subjected to an initial examination that will include a physiologic angle closure provocative test (the darkroom prone test), measurement of the anterior chamber depth by pachometry and determination of the axial length by the use of ultrasonic technique. The patients will then be followed expectantly for five years. It is expected that we will be able to more clearly determine the attack rate in this population and determine whether there are any correlations between the results of the provocative test or the biometric parameters and the subsequent incidence of acute attacks. This information could then provide the hard data that are needed to indicate whether specific Clinical Trials or other studies are indicated or justified.
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1 |
1996 — 2004 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ciliary Muscle Aging @ University of Wisconsin Madison
technology /technique development; nervous system; model design /development; eye; Primates; Mammalia;
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1 |
1997 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
H7, Latrunculin &Staurosporine On Contracted Monkey Ciliary Muscle: Glaucoma @ University of Wisconsin Madison
animal tissue; model design /development; eye; drug screening /evaluation; biological products; Primates;
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1 |
1997 — 1998 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
In Vitro Electrical Stimulation of Intact Enucleated Monkey Eyes @ University of Wisconsin Madison
technology /technique development; animal tissue; nervous system; model design /development; eye; Primates;
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1 |
1998 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Accommodation Mechanisms: Presbyopia: Ciliary Muscle @ University of Wisconsin Madison
OBJECTIVE: To understand the dynamics of accommodation and presbyopia RESULTS We implanted an electrode into the Edinger-Westphal nucleus of iridectomized cynomolgus monkeys. We determined real-time dynamics of ciliary muscle, lenticular and zonular movement in response to midbrain electrical and ocular pharmacological stimulation by digital image analysis of Scheimpflug slit lamp and goniovideographic recording. Eye movements were minimized by immobilizing sutures and botulinum toxin injections into the extraocular muscles. These studies are generating new information about the mechanisms of accommodation and the validity of classical vs non-traditional models of accommodation. FUTURE DIRECTIONS Further pharmacological stimulation of accommodation will be undertaken with atropine reversal to observe the maximal movements during the stimulation and reversal of accommodation while trying to maintain absolute ocular stability. KEY WORDS ciliary muscle, lens, zonule, botulinum toxin
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1 |
1998 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Cross Link Breaker Effects On Accommodation &Outflow Facility: Presbyopia @ University of Wisconsin Madison
OBJECTIVE: To determine whether cross-link breaker compounds can enhance accommodation and outflow facility in aging rhesus monkeys RESULTS We determined in rhesus monkeys aged 16 and 20 years, that cross-link breaker compounds variably enhance pilocarpine- or carbachol-induced accommodation and appear to produce long-term enhancement of the outflow facility response to pilocarpine. These compounds may be developed for treating presbyopia and enhancing the efficacy of glaucoma therapeutic agents which act by altering the morphology of the trabecular meshwork. FUTURE DIRECTIONS Addtional monkeys will be studied according to these protocols. KEY WORDS trabecular meshwork, ciliary muscle, presbyopia, glaucoma
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1 |
1998 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Ciliary Muscle Aging: Presbyopia @ University of Wisconsin Madison
OBJECTIVE: To understand the dynamics of accommodation and presbyopia RESULTS We implanted an electrode into the Edinger-Westphal nucleus of iridectomized rhesus monkeys between the ages of 8 and 16 yr. We determined baseline real-time dynamics of ciliary muscle, lenticular and zonular movement in response to midbrain stimulation by digital image analysis of Scheimpflug slit lamp and goniovideographic recordings. We performed various surgical ablations including extra-and intra-capsular lens extratcion, posterior capsulotomy and complete posterior capsulectomy following extracapsular lens extraction and regional zonulolysis, and have recorded some preliminary alterations in baseline real-time accommodation dynamics. These studies are generating new information about the pathophysiology of presbyopia in the rhesus monkey, the only known animal model for the human condition. FUTURE DIRECTIONS Further analysis will be done on images recorded from the surgically manipulated eyes to determine the role of the ablated structures in the accommodative process. KEY WORDS ciliary muscle, lens, zonule, capsulotomy , zonulolysis, midbrain, aniridia, electrode
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1 |
1998 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Age &Outflow Facility: Trabecular Meshwork: Glaucoma @ University of Wisconsin Madison
OBJECTIVE: To determine if atropine can eliminate the age-related decline in outflow facility in rhesus monkeys RESULTS We determined in rhesus monkeys ages 4-24 years, that baseline outflow facility decreases by 0.0160q0.0059 l/min/mmHg/yr. The average baseline facility was ~50% higher in the youngest (ages 4-=10 years) compared to the oldest (ages 21-25 yrs). Atropine decreased facility by 25% compared to baseline in the youngest monkeys but not at all in the oldest animals. The inability of atropine to completely eliminate the age-related facility decline indicates the presence of atropine-independent, facility relevant age-dependent changes in the trabecular meshwork itself such as loss of cells or build-up of extracellular material. Similar changes could contribute to the development of elevated intraocular pressure and glaucoma in aging humans. FUTURE DIRECTIONS We will study the age-dependence of uveoscleral outflow in rhesus; another fluid outflow pathway which may be compromised during the aging process. KEY WORDS atropine, trabecular meshwork, extracellular material, glaucoma
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1 |
1999 — 2001 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Effects of H 7 On Ciliary Muscle in Monkeys @ University of Wisconsin Madison
OBJECTIVE To determine the effect of agents which perturb the cytoskeleton of the trabecular meshwork so as to increase aqueous outflow on contraction of the ciliary muscle in vitro RESULTS H-7 and inhibits actin-based contraction in monkey ciliary muscle DISCUSSION Ciliary muscle strips isolated from the globes of rhesus monkeys which were being euthanized were mounted in a contraction chamber. After equilibration, 105M pilocapine hydrochloride, a just maximal dose for inducing contraction, was perfused throughout the chamber for 15 min. Successively higher concentrations of H-7, an agent which disrupts actomyosin contractility, were then added to the pilocapine bath. The change in force from resting tension was compared to that with pilocarpine alone. FUTURE DIRECTIONS Further characterization of the mechanism of action of H-7 and other cytoskeletally active compounds on anterior ocular segment functions will facilitate their development as antiglaucoma agents. KEY WORDS glaucoma therapy, pilocarpine, actomyosin FUNDING NEI EY02698 PUBLICATIONS Tian B, Millar C, Kaufman PL, Bershadsky A, Becker E, Geiger B H-7 effects on the iris and ciliary muscle in monkeys. Arch Ophthalmol. 116 1070-1077, 1998. [J]
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1 |
1999 — 2001 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Histochemical Mapping of Nadph Diaphorase in Monkey Eyes @ University of Wisconsin Madison
OBJECTIVE To localize in normal monkey eyes the enzyme involved in the synsthesis of nitric oxide RESULTS NADPH-diaphorase is widespread in monkey eyes indicating significant nitric oxide production in various ocular structures DISCUSSION Frozen sections of the eyes were mounted on slides, then fixed with 4% paraformaldehyde. NADPH diaphorase histochemistry was performed using nitroblue tetrazolium. Staining was found in the anterior and posterior ocular segment. In the anterior segment, reaction product was present in the corneal epithelium and endothelium, iris dilator and sphincter, lens capsule, ciliary muscle and non-pigmented epithelial cells and stroma of the ciliary processes. Trabecular meshwork staining was minimal if at all. In the posterior segment, staining was seen around choroidal blood vessels and choroidal nerves, and in the retinal pigmented epithelial, photoreceptor, bipolar, inner plexiform and ganglion cell layers FUTURE DIRECTIONS The role of nitric oxide in the normal physiology of aqueous humor formation and drainage and the pathophysiology of glaucoma will be studied. KEY WORDS nitric oxide, trabecular meshwork, ciliary muscle, ciliary processes FUNDING NEI EY02698, GRF PUBLICATIONS Chen Z, Gu Q, Kaufman PL, Cynader MS Histochemical mapping of NADPH-diaphorase in monkey and human eye. Curr Eye Res 17:370-379, 1998. [J]
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1 |
1999 — 2001 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Morphology of Ganglion Cells in Primate Retina During Glaucoma @ University of Wisconsin Madison
OBJECTIVE To examine the degenerative effects that prolonged elevation of intraocular pressure has on retinal ganglion cell morphology RESULTS In glaucoma, retinal ganglion cells undergo a pattern of degeneration that originates with the dendritic arbor and ends with shrinkage of the cell body. DISCUSSION The monkey model of glaucoma was combined with intracellular staining techniques using an isolated retina preparation. Midget and parasol cells from normal and glaucomatous eyes were labelled intracellularly and their axons, somas and dendritic fields were compared using confocal microscopy. In midget and parasol cells, the earliest signs of pressure-induced degeneration involved structural abnormalities associated with the denritic arbor. Reduction in axon thickness appeared later. Chronic elevation of IOP resulted in significant decreases in the mean soma sizes of midget and parasol cells. Comparisons of eyes with different levels of optic nerve damage showed the axons and dentritic fields of parasol cells were significantly smaller at lower cup to disc ratios than were those of midget cells suggesting a differential effect. FUTURE DIRECTIONS The lateral geniculate nucleus and visual cortex from these same animals are under study, to determine the effects of elevated IOP and retinal ganglion cell death on these regions of the brain. Attempts will be made to intervene in early functional deficits and atrophy with neuroprotective agents or gene therapy. KEY WORDS neuroprotection, intraocular pressure, retina, degeneration FUNDING Alcon Laboratories, AHAF, NEI EY11159, NEI EY02698 PUBLICATIONS Weber AJ, Kaufman PL, Hubbard WC Morphology of single ganglion cells in the glaucomatous primate retina. Invest Ophthalmol Vis Sci. 39:2304-2320, 1998. [J]
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1 |
1999 — 2001 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Accommodative Mechanism in Primate Eye @ University of Wisconsin Madison
OBJECTIVE To reanalyze the mechanism of accommodation in the primate eye in light of proposed novel mechanisms RESULTS The classical understanding of the primate accommodative mechanism was supported by our studies DISCUSSION Accommodation and disaccommodation were studied in cynomolgus and rhesus monkeys using both pharmacological stimulation and midbrain electrical stimulation. Movements of the ciliary processes and lens were imaged using goniovideography. Movements of the ciliary muscle and lens equator were imaged using ultrasound biomicroscopy. Videographic analysis showed the ciliary muscle moves forward and axially during accommodation releasing resting tension on the anterior zonular fibers, increasing tension on the posterior zonular fibers and moving the lens equator axially away from the sclera. During disaccommodation the ciliary muscle is pulled back to its resting position by the elasticity of the choroid and the posterior zonular fibers; increased tension on the anterior zonular fibers pulls the lens equator back towards the sclera. FUTURE DIRECTIONS Further analysis will be done on images recorded from the surgically manipulated eyes to determine the role of the ablated structures in the accommodative process. KEY WORDS ciliary muscle, lens, zonule, ultrasound, disaccommodation FUNDING NEI EY10213, Johnson & Johnson PUBLICATIONS Glasser A, Kaufman PL The accommodative mechanism of primate eyes revisited. Invest Ophthalmol Vis Sci 39(4):S311, 1998 (ARVO Abstract). [A] Glasser A, Kaufman, PL The Mechanisms of Presbyopia. In Refractive Surgery 1998 Reshaping the Future. American Academy of Ophthalmology Subspecialty Day 1998 Series, pp 141-146, 1998. [J]
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1 |
2000 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Aqueous Humor Dynamics &Aging @ University of Wisconsin Madison
OBJECTIVE To reanalyze the mechanism of accommodation in the primate eye in light of proposed novel mechanisms RESULTS The classical understanding of the primate accommodative mechanism was supported by our studies DISCUSSION Accommodation and disaccommodation were studied in cynomolgus and rhesus monkeys using both pharmacological stimulation and midbrain electrical stimulation. Movements of the ciliary processes and lens were imaged using goniovideography. Movements of the ciliary muscle and lens equator were imaged using ultrasound biomicroscopy. Videographic analysis showed the ciliary muscle moves forward and axially during accommodation releasing resting tension on the anterior zonular fibers, increasing tension on the posterior zonular fibers and moving the lens equator axially away from the sclera. During disaccommodation the ciliary muscle is pulled back to its resting position by the elasticity of the choroid and the posterior zonular fibers; increased tension on the anterior zonular fibers pulls the lens equator back towards the sclera. FUTURE DIRECTIONS Further analysis will be done on images recorded from the surgically manipulated eyes to determine the role of the ablated structures in the accommodative process. KEY WORDS ciliary muscle, lens, zonule, ultrasound, disaccommodation FUNDING NEI EY10213, Johnson & Johnson PUBLICATIONS Glasser A, Kaufman PL The accommodative mechanism of primate eyes revisited. Invest Ophthalmol Vis Sci 39(4):S311, 1998 (ARVO Abstract). [A] Glasser A, Kaufman, PL The Mechanisms of Presbyopia. In Refractive Surgery 1998 Reshaping the Future. American Academy of Ophthalmology Subspecialty Day 1998 Series, pp 141-146, 1998. [J]
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1 |
2000 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Effects of Adenosine On Isolated Ciliary Muscle in Monkeys @ University of Wisconsin Madison
OBJECTIVE To determine the effect of agents which perturb the cytoskeleton of the trabecular meshwork so as to increase aqueous outflow on contraction of the ciliary muscle in vitro RESULTS H-7 and inhibits actin-based contraction in monkey ciliary muscle DISCUSSION Ciliary muscle strips isolated from the globes of rhesus monkeys which were being euthanized were mounted in a contraction chamber. After equilibration, 105M pilocapine hydrochloride, a just maximal dose for inducing contraction, was perfused throughout the chamber for 15 min. Successively higher concentrations of H-7, an agent which disrupts actomyosin contractility, were then added to the pilocapine bath. The change in force from resting tension was compared to that with pilocarpine alone. FUTURE DIRECTIONS Further characterization of the mechanism of action of H-7 and other cytoskeletally active compounds on anterior ocular segment functions will facilitate their development as antiglaucoma agents. KEY WORDS glaucoma therapy, pilocarpine, actomyosin FUNDING NEI EY02698 PUBLICATIONS Tian B, Millar C, Kaufman PL, Bershadsky A, Becker E, Geiger B H-7 effects on the iris and ciliary muscle in monkeys. Arch Ophthalmol. 116 1070-1077, 1998. [J]
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1 |
2004 |
Kaufman, Paul Leon |
U13Activity Code Description: To support international, national or regional meetings, conferences and workshops where substantial programmatic involvement is planned to assist the recipient. |
Workshops On Clinical and Basic Ophthalmology Research @ Association For Res in Vision &Ophthal
DESCRIPTION (provided by applicant): This proposal requests financial support to organize two workshops, one in India and the other in the US, which will bring together ophthalmic researchers in India and the US. Based on these workshops, a number of binational research collaborations are expected to be initiated. The proposal emanates from an appreciation of several advantageous features obtained in India: (a) India has a far larger number of familially inheritable eye disorders, due to the prevalence of intra-community and consanguineous marriages. This offers the possibility of studying these conditions in greater depth and rigor. (b) Conditions that are relatively rare in the US- e.g., various forms of corneal dystrophy or glaucoma-are encountered more frequently in India. (c) Several eye care centers in India have been maintaining, over the years, detailed medical records of a very large number of patients, analysis of which would yield new leads and directions for research. (d) India offers excellent opportunities for clinical research, pilot human studies and fellowship training. (e) Chosen eye centers in India have researchers of high quality, rigor and track record, and they are already in touch (and in some instances, collaboration) with researchers in the US. (f) The research dollar goes farther in India, due to the lower costs of manpower and infrastructure. There is thus a mutually beneficial resource complementation between India and the US, which can be exploited to advantage through bilateral dialog and collaboration. It is with the view to promote such a dialog and mutual appreciation that we propose holding two meetings to bring researchers of the two countries together. We suggest the first be held in India and the second in the US- to enable the participants to gain first hand appreciation of the facilities available and to forge personal links. It is better that the two workshops are run within a short interval so as to save time and effort and build synergy. Based on these visits and discussions, collaborative research projects are expected to emerge. A list of broad topics or sub-fields could be identified as thrust areas.
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0.916 |
2004 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Effects of Compounds On Ciliary Muscle Contraction @ University of Wisconsin Madison
muscle contraction; uvea ciliary body; Primates; animal colony;
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1 |
2004 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Effect of Compounds On Outflow Facility in Organ-Culture @ University of Wisconsin Madison
Primates; animal colony; organ culture;
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1 |
2004 |
Kaufman, Paul Leon |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Components of the Hir Complex and Chromatin Assembly @ University of Washington
molecular assembly /self assembly; histones; intermolecular interaction; chromatin; biomedical resource;
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0.955 |
2004 — 2010 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Ciliary Muscle Aging and Presbyopia @ University of Wisconsin Madison |
1 |
2004 — 2006 |
Kaufman, Paul Leon |
U13Activity Code Description: To support international, national or regional meetings, conferences and workshops where substantial programmatic involvement is planned to assist the recipient. |
Arvo Annual Meeting @ Association For Res in Vision &Ophthal
DESCRIPTION (provided by applicant): The Association for Research in Vision and Ophthalmology (ARVO) annually conducts the principle eye research meeting in the world. Over 8,000 eye and vision researchers attend this meeting held annually in the United States. Nearly 5,500 abstracts, describing recent research efforts, are submitted and approximately 5,000 are accepted for presentation at the meeting. This meeting is targeted to clinical practitioners, research scientists, and medical education professionals and strives to meet the challenges and objectives set forth in the NEI National Plan: 1999-2003. The research presented at the ARVO Annual Meeting represents the latest developments in understanding, diagnosing, preventing and treating the many sight-threatening diseases and conditions.The dates for the next five ARVO Annual Meetings are: May 5 - 10, 2002; May 4 - 9, 2003; April 25 - May 30, 2004; May 1 - 6, 2005; April 30 - May 3, 2006
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0.916 |
2005 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Effects of Compounds On Outflow Facility in Organ-Cultured Anterior Segments @ University of Wisconsin Madison |
1 |
2005 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Effects of Compounds On Ciliary Muscle Contraction in Vitro @ University of Wisconsin Madison |
1 |
2005 — 2009 |
Kaufman, Paul Leon |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Core--Animal Model and Eye Organ Culture @ University of Wisconsin Madison |
1 |
2005 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Ciliary Muscle Stimulation and Outflow @ University of Wisconsin Madison |
1 |
2006 — 2011 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Glaucoma Therapy, Ciliary Muscle Contraction and Trabecular Outflow @ University of Wisconsin-Madison
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To determine whether compounds that generate nitric oxide (NO) can relax carbachol contracted or resting ciliary muscle (CM) in vitro. This is an indicator of whether this class of compounds may be useful in enhancing uveoscleral outflow as an approach for lowering intraocular pressure (IOP) in glaucoma. To determine the effects of compounds on in vitro CM contraction/relaxation, and on IOP in vivo. To utilize the monkey anterior segment in organ culture to investigate the effects of gene therapy and other molecules on trabecular outflow which may also be important for glaucoma therapy. To determine the effects of in vivo gene therapy to the anterior segment. Overexpression of proteins that alter aqueous humor outflow may lead to intraocular pressure reduction that is important for glaucoma therapy. Alternatively, elevation of intraocular pressure may lead to a new glaucoma model. Progress: The CM relaxation response to nitric oxide donors was blocked by pretreatment with ODQ, an inhibitor of the guanylate cyclase pathway, prior to administering a nitric oxide donor. NO compounds have potential value in therapeutic areas where relaxation or contraction of the CM is desirable, such as in the treatment of glaucoma. The monkey organ-cultured anterior segment (MOCAS) system is being utilized to determine the effects of pharmacotherapy and gene therapy on trabecular outflow which may subsequently be utilized for glaucoma therapy to decrease intraocular pressure. Overexpression of the protein cochlin, which is elevated only in human glaucoma, increases intraocular pressure (IOP) and decreases trabecular outflow. The IOP elevation response in MOCAS following treatment with transforming growth beta-2 (TGF[unreadable]2) is enhanced by including bovine serum albumin in the media. Studies to silence cochlin expression during TGF[unreadable]2 treatment will determine if cochlin induction is necessary for the TGF[unreadable]2-induced IOP elevation. Lentiviral vectors expressing genes that can potentially alter aqueous humor outflow have been injected into the anterior segment of living monkey eyes. Transduction of C3 transferase (capable of altering the actin cytoskeleton) in one eye did not alter the IOP. Ocular tissue is being examined to verify expression was present. Another gene, prostaglandin synthase (expected to enhance uveoscleral outflow), was delivered to the anterior segments of one eye of each of 5 monkeys. A transient reduction in IOP was detected in 3 of 5 eyes from 2 weeks to 5 months post-injection. Coexpression of green fluorescent protein was detectable in vivo for nearly 2 years. Tissues will be examined for PGFsynthase expression. Vitamin D applied topically to the eye lowers IOP. The mechanisms for this reduction are being investigated. This research used WNPRC Research Services. PUBLICATION: Lee E, Gabelt BT, Faralli JA, Peters DM, Brandt CR, Kaufman PL, Bhattacharya SK: COCH transgene expression by adenovirus in cultured human trabecular meshwork cells and its effect on outflow facility in monkey organ-cultured anterior segments. Invest Ophthalmol Vis Sci, Epub ahead of print, Nov 20, 2009.
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1 |
2007 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Accomodating Intraocular Lenses @ University of Wisconsin Madison
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To determine the accommodative ability of intraocular lenses in rhesus monkeys following central stimulation.[unreadable] [unreadable] Electrodes were implanted into the Edinger Westphal nucleus of 4 rhesus monkeys so that accommodation could be [unreadable] stimulated centrally. The lens substance was replaced with artificial lenses designed by NuLens. The ability of these lenses [unreadable] to accommodate, change shape and position after central stimulation was determined using refractometry, ultrasound [unreadable] biomicroscopy and goniovideography. Accommodation was induced by 8.0 diopters during stimulation. Thus, these lenses [unreadable] have the potential to reverse the onset of presbyopia with age. This research used WNPRC Research Services.
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1 |
2007 — 2011 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Lens Laser Strategies For Presbyopia @ University of Wisconsin-Madison
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To determine the accommodative ability in older rhesus monkeys following central stimulation before and after lens lasering. RESULTS: Currently, monkeys that received laser treatment of the lens are being housed for long-term observations. Previously, an electrode was implanted into the Edinger- Westphal nucleus of each of 2 older rhesus monkeys so that accommodation could be stimulated centrally. In addition, 4 young rhesus monkeys were used as test subjects to calibrate the femtosecond laser. Baseline testing was completed prior to determination of the effects of lens lasering on the accommodative response. The femtosecond laser procedure appears to be well tolerated in the monkey eye. However, small retinal burns (1-2 mm in size) were noted in 2 out of 5 monkeys lasered. The ability to obtain refractive measurements with the Hartinger coincidence refractometer was not compromised by the femtosecond laser procedure beginning 24 hours after lasering. Animals did not exhibit abnormal behavior or evidence of pain or discomfort. Slit lamp examinations are performed bi-annually in the remaining four rhesus monkeys. All animals maintain normal vision. Presently the animals continue to be monitored and future experimental plans are being considered. This research used WNPRC Animal and Pathology Services.
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2008 — 2011 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Accommodating Intraocular Lenses @ University of Wisconsin-Madison
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To determine the accommodative ability of intraocular lenses in rhesus monkeys following central stimulation. Electrodes were implanted into the Edinger Westphal nucleus of 6 rhesus monkeys so that accommodation could be stimulated centrally. The lens substance was replaced with artificial lenses designed by NuLens. The ability of these lenses to accommodate, change shape and position after central stimulation was determined using refractometry and ultrasound biomicroscopy. Accommodation of 8.0 diopters was induced during stimulation. Thus, these lenses have the potential to reverse the onset of presbyopia with age. It was determined that four animals with inflammation due to the intraocular lens surgery and severe corneal opacification required a corneal transplant in one or both eyes. Donor monkeys were located and corneal transplants were performed. Four months post transplant, slit lamp examination (SLE) revealed no rejection signs in two animals, but all corneas appeared slightly hazy. The haziness was more pronounced in the bilaterally treated monkeys. Dr. Neal Barney, one of our corneal specialists, examined these animals numerous times since their transplant procedure. He felt that these animals would maintain slightly hazy corneas, but had successfully tolerated the transplant procedure with an appearance and behavior consistent with improved vision. Since no measurable accommodation data was gathered in the two animals with more pronounced cornea haziness, those animals were euthanized. Three rhesus monkeys maintain accommodation from 3 to 8 diopters for at least eight months post IOL insertion. Experiments are conducted quarterly to document the NuLens IOL functionality. Potentially two additional rhesus monkeys will receive an electrode implant followed by the next generation NuLens IOL. This research used WNPRC Research Services.
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2009 — 2010 |
Kaufman, Paul L. |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Extra-Lenticular Aspects of Accommodation and Presbyopia @ University of Wisconsin-Madison
DESCRIPTION (provided by applicant): Our research into the pathophysiology of presbyopia, the age-related loss of the eye's ability to focus on near objects, has found evidence in a monkey model that the aging ciliary muscle is restricted in accommodative movement by its posterior elastic attachments. In the Parent R21 grant application, our goal is to determine the role of the posterior zonule in accommodation and presbyopia. In this supplement application (Notice number: NOT-OD-09-058) we wish to expand our investigation by determining the role of the choroid, another of the ciliary muscle's posterior elastic attachments, in restricting the accommodative movement of the ciliary muscle with age. Human accommodative amplitude (the ability of the eye to focus on near objects) declines progressively with age, beginning in the second decade of life and perhaps earlier, and is completely gone by age 50-55 years.[1] No individual appears exempt, making presbyopia (literally, "old eye") the most common ocular affliction in the world. Although certainly not a blinding condition, and correctable by various optical means, presbyopia's cost in devices and lost productivity is substantial.[2] Although much useful and relevant information has been garnered from studies in living and postmortem human eyes, the invasive techniques required to answer some of the most critical questions cannot be employed in the living human. While the eyes of subprimate species either do not accommodate or accommodate by mechanisms very different from that of the human,[3] the accommodative apparatus of the rhesus monkey eye is very similar to that of the human eye.[4] [5] [6] Rhesus accommodation declines on a relative time scale that is essentially identical to that of the human.[5] Our group has utilized the rhesus monkey to contribute significant new information relevant to presbyopia pathophysiology. In this model, we have demonstrated that the ciliary body excursion during accommodation diminishes with age, probably due to an age-related decrease in elasticity of the posterior attachments.[7, 8] This restricts the degree of accommodative amplitude. We have also shown that the movement of the lens equator decreases with age, again resulting in reduced accommodative amplitude.[7, 8] Further, although histological data from excised postmortem human eyes shows the older human ciliary body at rest in an anterior/inward position, we have preliminary imaging data that suggest this may not be the case in vivo (see Preliminary Studies). Classical teaching attributes presbyopia to "lenticular sclerosis," or "lens hardening,"[2, 9-15] so that the lens cannot change shape, but the definitive mechanism that results in presbyopia remains elusive. In search of a way to restore some degree of accommodative amplitude, we hypothesize that age-related immobility of the muscle is due to posterior restriction. Further, if these posterior restrictions are eliminated, mobility of the muscle can be restored and facilitate the function of accommodating intraocular lenses (IOLs). PUBLIC HEALTH RELEVANCE: Our goal is to determine what role the extralenticular tissues play in the pathophysiology of age- related ciliary muscle immobility in the non-human primate, and to determine whether the resulting model is relevant to human presbyopia. This may be crucial in enabling the function of next- generation intraocular lenses (IOLs).
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2009 — 2010 |
Kaufman, Paul Leon |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Aqueous Humor Dynamics Studies in Vivo and in Vitro @ University of Wisconsin-Madison
DESCRIPTION (provided by applicant): New approaches to lower intraocular pressure, a significant risk factor for the progression of glaucoma, will be investigated. Outflow through the trabecular meshwork will potentially be enhanced by ILK, PI3K and Src kinase inhibitors, which have been shown to alter the cytoskeleton and cellular adhesions of trabecular meshwork (TM) cells in culture. The effects of these compounds on intraocular pressure (IOP) and outflow facility will be studied in organ-cultured anterior segments and in monkey eyes in vivo. Gene therapy approaches will be utilized to lower IOP by enhancing outflow via the uveoscleral pathway. One of the current most effective pharmacotherapies for glaucoma is based on derivatives of prostaglandin (PG)F2a which binds to the FP receptor leading, in part, to enhanced matrix metalloproteinase (MMP) synthesis. This, in turn, alters the composition of the extracellular environment of the ciliary muscle (CM) and sclera leading to an enhancement of uveoscleral outflow. Lentiviral vectors carrying genes for PGF synthase and for stromelysin (MMP-3) will be injected into the anterior segment of monkey eyes in vivo and the effects on IOP and uveoscleral outflow will be assessed. PGF2a and MMP-3 production will also be assessed in the aqueous humor and in the media from human TM and CM cells transduced in vitro. A final objective will be to investigate in vivo the role of the neurotransmitter, nitric oxide, in regulating IOP, aqueous humor inflow and outflow. To simulate the dramatically reduced levels of nitric oxide synthase (NOS) in the anterior segment in glaucoma, a short-term equivalent of nitrergic denervation will be created in monkeys in vivo following topical or intracameral dosing with the non-selective NOS inhibitor L-NAME and/or the relatively selective neuronal nitric oxide synthase inhibitors 7-NI and/or NPLA. The effects on basal pupil diameter, refraction, aqueous humor formation and/or outflow facility will be determined. Conversely, these parameters will be measured in response to the nitric oxide donor, SNP, in the presence and absence of cholinergic and/or adrenergic blockade. These results will provide important insights for developing new therapies to lower IOP. Studies will be conducted in living nonhuman primates, in vitro in organ-cultured anterior segments and in trabecular meshwork cells and ciliary muscle cells in culture. The following techniques will be employed: aqueous humor formation by fluorophotometry;outflow facility by two-level constant pressure perfusion;uveoscleral outflow calculated from isotope dilution and accumulation measures;IOP by Goldmann applanation tonometry;refraction by Hartinger coincidence refractometry;pupil diameter via vernier calipers;gene expression in vivo by coexpression of GFP fluorescence detected by a custom designed research microscope system;gene product detection by Western blots and enzyme immunoassays and immunohistochemistry. PUBLIC HEALTH RELEVANCE: The proposed studies will investigate new approaches to lower intraocular pressure that may be further developed for glaucoma therapy. The first two objectives are to enhance aqueous humor outflow through the two known outflow pathways using novel small molecules (PI3K, ILK and Src kinase inhibitors) to enhance trabecular outflow, and gene therapy (lentiviral vector mediated delivery of genes that increase production of enzymes (prostaglandin synthase and stromelysin)) to increase uveoscleral outflow. A third goal is to better understand the role of an important neurotransmitter (nitric oxide) in regulating normal and drug induced changes in aqueous humor formation and drainage in order to provide the basis for novel glaucoma therapies.
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2016 — 2020 |
Kaufman, Paul L. |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Core Grant For Vision Research - Core#3 Animal Models and Organ Culture @ University of Wisconsin-Madison
CORE 3: ANIMAL MODELS AND ORGAN CULTURE ABSTRACT The goal of the Animal Models Core is to facilitate the use of animals and eye organ culture to study visual function and visual diseases by qualifying NEI funded researchers. We also assist non-qualifying investigators in generating preliminary data for funding. This is accomplished by providing expertise in animal models for glaucoma, retinal degeneration, ocular vascular disease, eye organ culture, and infectious diseases and includes animal handling and anesthesia. We also provide expertise and equipment necessary for the evaluation of visual function and disease including, ERG, multifocal ERG, OCT, retinal imaging, IOP and outflow facility determination. Because we are one of the only, if not the only, Vision Research Core with an associated Regional Primate Center, we are in a unique position to provide access to vision research involving non-human primates. As a result, this core has also facilitated vision research by investigators at other institutions and their papers cite this core.
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2016 — 2019 |
Kaufman, Paul L. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Extralenticular Aspects of Accommodation and Presbyopia @ University of Wisconsin-Madison
? DESCRIPTION (provided by applicant): We seek to continue and advance our group's study of human accommodative amplitude (the maximum ability of the eye to focus on near objects) and accommodative loss (presbyopia, literally old eye) the most common ocular affliction in the world. Through our group's recent research in the monkey model, we have made the significant discovery of the existence of new extralenticular-zonular structures (PVZ INS-LE strands), which are linked to accommodation. In particular, we hypothesize that these structures may act as a strut to the posterior lens equator during accommodation and thereby facilitate accommodative lens thickening. Likewise, preliminary studies in the monkey eye suggest cistern-like structures in the vitreous, which we hypothesize play a role in fluid exchange between the anterior and posterior segments during accommodation. Despite these novel discoveries, it is clear that aspects of accommodation and the definitive mechanisms that result in presbyopia are yet to be fully determined and studied. Likewise, we hypothesize that age-related immobility of the ciliary muscle is due to posterior restriction. We postulate that, if cerain posterior restrictions are eliminated, mobility of the muscle can be restored and can facilitate th function of accommodating intraocular lenses (IOLs). The goals of our proposed research are: 1) To investigate and define the new players in the posterior restriction of the ciliary muscle, elucidation of which may be crucial in preserving forward ciliary body (FCB) movement and in enabling the function of the next-generation accommodating IOLs; 2) Determine the posterior extent of choroid/retina accommodative movement (i e., optic nerve region) with implications for accommodative mechanism and biomechanical models; 3) Define the role that the various intraocular structures (i.e., anterior hyaloid, vitreous zonule, vitreous cistern-like structure, PZ INS-LE strand, Hannover's Canal) play during accommodation and their change with age in the rhesus monkey (due to similarities to the human eye); and 4) To identify a biological target for human presbyopia therapy, albeit not necessarily a therapeutic surgical procedure for that target in the human eye. We believe the identification of, and proposed continued research of, these and associated structures will affect the understanding of how the eye accommodates earlier in life, and thereby change how we understand and treat presbyopia. The energy and excitement in our group is high, based upon our recent progress and the promises they hold for those with presbyopia.
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