John S. Werner - US grants

The proposed research is designed to analyze the processes underlying the changes in infant visual attention that occur as a function of experience with a stimulus. Preliminary studies show that at least two independent processes are involved: A memorial process controlling response decrements (habituation), and an arousal process controlling response increments (sensitization). In contrast to most previous work, which emphasized only the memorial process, the present project focuses on the sensitization process. One avenue of research will identify the stimulus determinants of the sensitization process. A technique called linear systems analysis is employed, which considers the "fit" between the physical properties of the stimulus and the characteristics of the infant's visual system (as estimated from contrast sensitivity). The most sensitizing stimuli may be those that closely match the infant's perceptual capabilities. Another line of research will investigate the contribution of sensitization to visual attention of different aged infants. A relatively high level of sensitization could have as much to do with the slow rate of response decrement observed with very young infants as does any memorial deficit. Finally, the interaction between sensitization and learning processes will be studied. Sensitization prolongs visual fixation and may, therefore, lead to better encoding of visual pattern stimuli. If two (or more) processes modulate infant visual attention, then the interpretation of infant visual fixation data must be reconsidered: Change in visual attention reflect not only cognitive factors, but also sensory and motivational factors. Researchers interested in the clinical use of visual fixation data must take into account the multiple determining factors involved.

Senescent eharjges to human visionhave beenwell documented, butthe factorsresponsible for these changesareonly partially understood, Theproposed research is intended to provide fundamental data on aging of the human visual systehl usfrig pftychophystaalmethods that separatethe relative contributions of optical and neural mechanisms. Because imicholthe sensitivity loss of cone pathwaysoccursat early stages of processing, wewillexamine age-related kissesin cone photoplgmenlopticaldensity in thecentral 10[unreadable]of retina for normal andsex-linked dichromats whosegenes havebeen sequanced to look for genetic correlates of photopfgment optical density andreceptor longevity," It is hypothesized that senescent changes in conephotopigment density will notbeuniform with retinal eccentricity, and the outcome of triteexperiment witt be important for theoretical and practical reasons.A secondaimof the proposed researchteto quantify senescent changes in the temporal properties of isolated color mechanisms through measurements of the temporal contrast sensitivity function and the impulse responsefunction. Thethird aimis to determine senescent changes Inspatial properties of isolated color mechanisms through measurementsof thearea of complete spatial summation (Rteoo'aarea). Age-relatedchanges in spatial summation are predicted basedonour previous work,and documented tossesof retinal ganglioncells with age, but wedo not knowwhetherthis will befound in all color pathways,the fourthaimis atsoconcernedwith spatial properties erfrodandcone pathways,butwill measure spatiallcontrast sensitivity functions for isolated mechanisms. Thefinal aim is basedon our previouswork showing thai, at[unreadable] perceptual level, the visual systememploys mechanisms that compensate, in part, for lossesin sensitivity attowierlevels. Color appearance mechanisms will beprobed by measurementsof age-relatedchanges in chromatic perceptive fieldsoverareas of retina associated wit) different relative tosses of cones andganglion cells. Sensitivity of isojateo* cone mechanisms and color appearance wffl be measuredfor individuals beforeand aftercataract extraction andimplantation of intnvocular lenses.Theseexperiments will provide newinformation on mechanisms that promote color constancy deapttesubstantialvariations inthe retinalimage dueto lenticular senescence. Each ofthese aims willincWdeidetailed tests of individualyounger andolder observers, and measurements on selected conditions with a large groupof individuate rangingin agefromapproximately 12to 85years. In addition to providing basic dataon the aging visualsystem, the experiments will provide probesfor models of howthe visual system adaptsand compensates fof degradations in the optical and neural images that occurwith senescence anddisease. PERFORMANCE Slti(8) forpanfeatfoa <%, fluff) University of California, Davis Medical Center Department of Qphthaimotoov 4860 YStreet. Suite 2400 Sacramento, CA 95817 Name :':;;''[unreadable]'.]'.'.' Werner, John Sfeon Knau,HolgerK, SchefrJn, BrooJceiE. Handel, James Ti Morse, Uwrence Neitz, Maureen Shinomori, Keizo onPage11. Vmcontinuation pagesu itMdMtoprovidetherequiredinformation intheformat shownbelow. Organization Role on Project UC-Davis Medical Center Principal Investigator DC-Davis Medical Center Research Associate UC-Davis Medical Center Research Associate UC-Davis Medical Center Collaborator/Consultant UC-Davis MedicalCenter Collaborator/Consultant Medical College of Wisconsin Collaborator Medical College ofWisconsin Collaborator Kochi University of Technology, Japan Collaborator PHS338 (Rev. 4/98) Pag* 2 BB Number fMJQSstameua^itf atMebottom ttwougroiftth[unreadable]Bppllo[unreadable]9on.DonauMsuHl)MS[unreadable]uchM3[unreadable],3b. cc Prindpal InvBsttQfttof/Prooram Director (Last, tint. mticHo):. Wemer, John Simon iframeof th* principal investigator/programdirector at the top of each printed pageandeachcontinuation page. (Fortype specifications, see [unreadable]on page6.) RESEARCH GRANT TABLE OF CONTENTS [unreadable] . i PageNumbers Face Page .,4 1 Description,

DESCRIPTION (Investigator's Abstract): Changes in human vision throughout the can be attributed are now beginning to be understood. It is known that the intensity and spectral composition of the retinal stimulus changes over the life span due to age-related increases in ocular media absorption. The sensitivities of the cone receptors continuously decline from age 10 through adulthood. These changes in pre-receptoral and receptoral processing will necessarily alter the input to post-receptoral processes subserving color appearance. The purpose of this research is to study post-receptoral processing of chromatic and achromatic information throughout the life span, with emphasis on the elderly (60-80 years). Test conditions will be used that allow the separation of pre-receptoral, receptoral and post-receptoral mechanisms. Color discrimination will be measured under two conditions; one that depends on variation only in short-wave cone activity and one in which short-wave cones do not contribute to color discrimination. These data will indicate whether age-related changes in chromatic discrimination are due to selective loss in one particular pathway. To determine relative age-related changes in chromatic and achromatic pathways, opponent-chromatic response functions, saturation-scaling, and brightness-matching functions will be measured. These data will not only document age-correlated changes in individual mechanisms, but will also be used to test models of the relations between processing at different levels, particular wavelength discrimination. All of the psychophysical tests will include observers ranging in age from 10 to 80 years. Complete psychophysical functions will generally be measured for a group of 10 observers and selected spectral points will be measured for an additional 30-40 observers. Psychophysical testing will also be carried out with pseudophakic patients having intra-ocular lens implants that either transmit or absorb ultraviolet radiation to further test the hypothesis that ultraviolet light exposure contributes to age-correlated changes in short-wave cone sensitivity, and hence attenuates inputs to post-receptoral processes. These data may reveal an important environmental contribution (light itself) to individual differences in aging. Since light exposure can be partially controlled, the data may have public health significance for aging populations. This research is thus concerned with separating the optical and neural mechanisms that mediate age-correlated changes in the perception and processing of color. These studies may contribute to our understanding of the factors that contribute to individual variation in aging of the human visual system.

DESCRIPTION: Changes in foveal color vision processing throughout the life span are now well-documented, but the factors responsible for these changes are only partially understood. The purpose of this research is to determine the optical and neural factors that contribute to age- related changes in human color vision. Senescence of foveal and parafoveal processes will be compared. Visual performance at a neural level will be quantified using corrections for light losses due to age- related changes in the ocular media and to individual variation in macular pigment density. Sensitivity of isolated cone pathways will be measured at several retinal loci, and spatio-temporal summation experiments will be conducted to identify possible changes in neural ,organization such as increased neural noise, reduction in quantum catch and changes in cell numbers and morphology. Color appearance will be quantified by measurement of unique hues. Scotopic sensitivity and spatial summation will also be tested because of losses in rod numbers with advancing age. Tests of sensitivity and color appearance will also be conducted before and after cataract extraction and implantation of intraocular lenses. These experiments will provide further evidence pertaining to neural compensation which promotes color constancy despite lenticular senescence. The research will permit an evaluation of whether macular pigment plays a protective role for the retina and whether it is the basis for some individual differences in normal aging. It will contribute to our understanding of possible neural reorganization associated with losses of photoreceptors and ganglion cells. It will also provide fundamental data describing senescence of visual processes.

DESCRIPTION (provided by applicant): Continued support is requested for interdisciplinary training in the vision sciences at the University of California, Davis. Training is provided by 45 vision scientists (31 preceptors and 14 associate preceptors) across 14 departments that will provide a strong foundation in one or more basic sciences. The goal of the training program is to produce vision scientists who will be capable of establishing independent research programs that will address significant problems in vision science. It will operate under the auspices of existing graduate programs at UC Davis as they offer the broad flexibility needed to achieve our training objectives. Among our 300 pre- and postdoctoral vision science trainees in the past ten years (38 of whom were partially supported by this T32), 90% are active in research through continuing training or in career positions. Among those who have completed all training, 82% are active in research and/or teaching positions at some 71 different colleges, university basic science departments and schools of medicine or veterinary medicine. The training program requests support for 4 predoctoral students (for two years each; 8 slots) and 1 postdoctoral trainee (for one year) to be selected by an Advisory Committee. Internal support mechanisms and extramural grants will be used for the other years of training. The trainees will participate i one or more of five overlapping areas in which our preceptors are clustered: (1) molecular & cellular biology, retinal electrophysiology, and genetics, (2) anterior segment anatomy and physiology, (3) molecular and cellular retinal imaging, (4) systems visual neuroscience, and (5) functional imaging, computational modeling and perception. Each of the 31 preceptors has an active program of vision science research, a strong commitment to training, and extramural funding. Program resources are augmented by a strong institutional commitment, the Center for Visual Sciences and an NEI Core grant. The training program draws on the rigorous research training of the admitting programs, but also requires a one-year course that covers the broader vision sciences and clinical vision science. Graduate trainees will be supported only after their first year of graduate training and will thus be a highly selective group that has completed much of their basic science curriculum. All trainees will participate in an active colloquium series in he vision sciences, Center for Visual Sciences symposia, journal clubs and training in the ethical conduct of research. All trainees will be engaged in vision science research that will be presented at national meetings and submitted to peer-reviewed journals.

DESCRIPTION (provided by applicant): The purpose of this BRP is to develop and evaluate technology for three-dimensional imaging of cells in the living eye, and to use this novel technology to understand changes in cell layers associated with the most common diseases leading to world-wide blindness, including age-related macular degeneration and glaucoma. Partners at four institutions will contribute to instrumentation that combines adaptive optics (AO), providing high lateral resolution, with optical coherence tomography (OCT), providing high axial resolution. The lead institution is the University of California, Davis (John S. Werner, PI). Both at UC Davis and at Indiana University (Donald T. Miller, site PI), AO-OCT instrumentation will be developed and tested. Duke University (Joseph Izatt, site PI) will develop novel OCT approaches that will be incorporated, while Lawrence Livermore National Laboratory (Scot Olivier, site PI) will provide cutting-edge advances in AO. These AO-OCT instruments will permit human in vivo imaging with sufficient resolution and contrast to visualize the smallest of cells in the human retina. In the previous project period we have used AO-OCT to create volume images of structures previously only visible with histology, including the photoreceptor outer segments, Fibers of Henle, individual optic nerve fiber bundles, detailed structures within drusen of macular degeneration patients, and fine structure of the lamina cribosa of the optic nerve. In this renewal, we propose to solve new technical issues to more fully tap the potential and functionality of AO-OCT. The engineering goals are directed toward increasing contrast of cellular structures by use of autofluoresence, birefringence, the incorporation of extreme AO techniques, and functional changes associated with blood perfusion, hemoglobin oxygen saturation in the retinal vasculature as well as electrical changes in neuronal cell volumes. Considerable effort will be devoted to three-dimensional visualization and segmentation over retinal volumes of larger lateral and axial extent than previously possible. The engineering goals have parallel clinical aims for improving our understanding of the cellular changes associated with markers for age-related macular degeneration and glaucoma. These advanced imaging techniques will be deployed for evaluating the changes in the retina and optic nerve resulting from novel therapies for rescuing retinal layers from the leading causes of blindness.

Abstract Not Provided.

DESCRIPTION (provided by applicant): This application seeks continued support for a Vision Core Grant that has facilitated the research efforts of vision scientists at the University California, Davis for the past ten years. During the decade that the CORE has been funded there has been remarkable growth in the visual sciences on this campus. This is demonstrated by a substantial increase in the number of faculty engaged in vision research as well as NEI funded grants. Since the last competitive renewal, the administration has approved the establishment and funding of a Center for Visual Sciences, which provides a means for unifying our community of vision researchers. Building on this strength, we have redesigned the currently funded four modules to better serve the needs of our NEI funded investigators. The proposed modules are: (i) Software Engineering (W. Martin Usrey, Director), (ii) Histology and Phenotype (Paul FitzGerald, Director), (iii) Retinal Anatomy and Physiology (Andrew Ishida, Director), and (iv) Instrumentation (John S. Werner, Director). These four modules provide facilities and services of greatest benefit to the largest number of our vision scientists. The CORE administrative structure includes an Advisory Committee comprised of the Principal Investigator, the four module directors, the director of the Center for Visual Sciences, as well as the Chair and research director of the Department of Ophthalmology &Vision Science. Issues involving CORE facilities and usage are discussed at quarterly meeting of the Vision Science Research Group that includes all members of our vision science community. Priorities for use of CORE facilities have been carefully honed and made available to all investigators, and this has mitigated potential scheduling conflicts. The administration of UC Davis has been and continues to be very supportive of vision research. This is demonstrated by the funding of the Center for Visual Sciences, the addition of five ophthalmology research faculties, resulting in the recent name change to Ophthalmology &Vision Science, the generous start-up packages for new vision faculty, and a pledge of more than $180,000 for equipment needs for CORE facilities during the next grant period.

DESCRIPTION (provided by applicant): Senescent changes in human vision have been well documented, but the factors responsible for these changes are only partially understood. The proposed research is intended to provide fundamental data on aging of the human visual system using methods that separate the relative contributions of optical and neural mechanisms. This research builds on a program demonstrating that age-related losses in the visual pathways have a profound effect on early stage processing but are compensated to a surprising degree to maintain constancy of perception. The overarching theme of the proposed research is to understand temporal dynamics of adaptation, compensation and neuroplasticity at several time scales and levels of processing. Aim 1 compares normal aging and early-stage age-related macular degeneration. Temporal dynamics and retinal adaptation mechanisms will be studied under scotopic and photopic conditions using the full-field and multifocal ERG. Response interactions will be analyzed to understand functional sites of aging and adaptation in the outer retina. These functional data will be correlated with sequenced opsin genes and complement factor H alleles, and with ultra-high resolution images to study photoreceptor numbers and outer retinal morphology, including relations with drusen. Aim 2 will explore temporal dynamics and gain mechanisms under conditions that are dominated by the response of magno-, parvo- or konio-cellular pathways. The hypothesis to be tested is that the OFF subdivisions of these pathways are affected more in senescence than are the ON subdivisions. This will be evaluated by measuring a psychophysical impulse response function and by a psychophysical probe to quantify age-related changes in gain control mechanisms of magno- and parvo-cellular pathways. Aim 3 is concerned with putative cortical compensation mechanisms. While most methods define the adaptation midpoint, the first experiment for this aim is concerned with how adaptation adjusts the range or variance of color signals along cardinal and higher-order color axes. A second study will measure adaptation to higher- order ocular aberrations using a custom adaptive optics phoropter. Finally, patients with diabetic retinopathy will be tested following retinal photocoagulation therapy to determine whether some losses in vision are compensated by expansion of areas subserving spatial summation, similarly to enlargements of spatial summation areas associated with age-related losses in photoreceptors and ganglion cells. These experiments are guided by current hypotheses about the manner in which visual performance may be affected by normal senescence and by age-related macular degeneration and diabetic retinopathy. In addition to providing basic data on the aging visual system, the experiments will provide probes for models of how the visual system adapts and compensates for degradations in the optical and neural images that occur with senescence and disease.

Molecular Construct and Packaging: is a new core directed by Marie Burns to provide molecular construct and viroid particle production, focused on producing tools needed for optogenetics and perturbation of gene expression in vision research. To facilitate the development of this core, the Dean of the Medical School has provided salary support for a highly experienced professional staff member (50% FTE for 1 year). 11 R01i investigators and two new faculty are anticipated to be moderate to extensive users.

Truly innovative vision research can rarely rest solely on turn-key equipment, and most laboratories solve unique problems that require custom fabrication. This is usually designed to exacting specifications of the sort that only a professional machinist or electronics engineer can provide. The purpose of this core is to provide support for custom design and construction of high-tolerance laboratory equipment. There are two shops whose use is anticipated for the majority of services in the upcoming 5-year period: UCD Engineering Shop: This is a 1000 ft 2 facility located in Bainer Hall, UC Davis, with several full-time machinists on staff. Equipment includes: 1. Turning - Conventional operations up to 19-inch diameter and 72-inch length. Six conventional lathes of various sizes with taper attachments and digital read-outs. 2. Drilling - Four conventional drill presses. 3. Milling - Two conventional vertical knee and two universal with horizontal spindle mills, both with associated special tooling. 4. CNC Machinery - One three-axis bed mill, one two-axis Bridgeport knee mill and one three-axis Bridgeport knee mill. These machines are all CAD/CAM interfaced using Feature Cam software. 5. Surface Grinding - One precision flat surface grinding machine. Two Dumore cylindrical grinding attachments for lathes. 6. Shears, Punches, Brakes, Rolls, Benders and Knotchers, Presses - Two sheet metal shears with lengths of cut to 72 inches and material thicknesses up to 0.104 inches in stainless steel, 0.134 inches in mild steel and 0.187 inches in aluminum. 7. Welding, Brazing, Soldering and Cutting Processes - Procedures: GMAW, GTAW, SMAW, Gas Welding, in accordance with ASME and AWS standards in various ferrous and non-ferrous materials; brazing, silver soldering, soft soldering; flame and plasma cutting processes; thermoplastic welding; heat treating furnace for minor heat treating operations. 8. Sand blasting and bead blasting booths 9. Spray painting - hooded booth and drying oven 10. Full assortment of hand tools powered and non-powered 11. Metal cutting handsaw 12. Marvel material cut-off saw 13- 3-ton overhead crane . 14. Wood shop facility - fully tooled 15. Electrical/electronic design engineering 16. Mechanical/design development engineering support UCD Physics Electronics Shop: This shop, located in the Physics Building, provides design, prototyping and production of one-of-a-kind electronic devices. The shop maintains a storeroom of electronic parts, and electronics engineers fabricate analog and digital circuits, circuit boards and other electronics {e.g., the pixel detector that was part of the Large Hadron Collider in CERN, Switzerland). The staff has extensive experience in creating seamless electronic interfaces for machined devices for data acquisition and instrument control systems. They are also skilled in retrofitting instruments, and repairing and calibrating electronic and electromechanical equipment for our NEI investigators

A. Research Plan The Small Animal Ocular Imaging Core (SAOIC) comprises a suite of noninvasive imaging services for living mice and rats, including reflectance and fluorescence fundus imaging with a Micron III? mouse digital camera system, optical coherence tomography (OCT), adaptive optics (AO) combined with OCT, scanning laser ophthalmoscopy (SLO) and AO-SLO using custom-built optical systems. These techniques allow widefield to cellular-level resolution imaging of the anterior segment, of the fundus vasculature with fluorescence angiography and phase-variance OCT, and of retinal neuronal and RPE cell structure and function. Mice are the most widely used mammalian model for the investigation of fundamental retinal physiology and cell biology, retinal disease and therapeutics. Noninvasive imaging of mice has become increasingly important in eye research, with commercial instruments such as Phoenix Ltd's Micron III widefield fundus camera (available in our facility) being widely employed. UC Davis has outstanding mouse husbandry facilities, and indeed, has one of the NIH-supported Mutant Mouse Regional Resource Centers (described above). The value of the SAOIC is further enhanced by the Molecular Construct and Packaging Core of this grant, which will provide for the production and packaging of DNA vectors for delivery to the mouse eye either by neonatal injection and iontophoresis, or by viral (AAV) packaging and intravitreal injection.

Research Plan Vision science experiments are becoming increasingly complex with tremendous demands being placed on interfacing specialized pieces of equipment, executing moment-by-moment dynamic control over stimulus delivery and data acquisition, and performing real-time analysis on streaming data. In addition, the increasing use of multielectrode recording systems and high-resolution imaging of neuronal morphology and activity has forced laboratories to consider the handling, storage, and computing requirements that these large datasets require. To meet these needs, the Software Engineering Core provides professional programming services to NEI funded laboratories that could not be supported by individual R01 awards. Moreover, by meeting the research needs of the faculty with a common resource, software can be engineered with the overarching goal of increasing data sharing and collaboration. Indeed, almost all of the applications and resources provided thus far are shared between multiple Core faculty, and numerous applications have been provided to NEI-funded investigators at other universities, including Dartmouth Medical School, University of California, Berkeley, University of Southern California, University of Pennsylvania, Mount Sinai School of Medicine, and Louisiana State University Medical School. The Software Engineering Core also published highly innovative software tools in a peer-reviewed journal for the broader vision science community.

DESCRIPTION (provided by applicant): Three aims are proposed to study the chorioretinal complex (choroid, choriocapillaris, Bruch's membrane, retinal pigment epithelium, photoreceptors) in age-related macular degeneration (AMD). Each aim includes both technical goals involving optical imaging and tests of hypotheses related to the pathogenesis of this disease. Aim 1 will use phase changes between successive optical coherence tomography (OCT) B-scans (frames) to visualize the vascular layers behind the retina, specifically the choriocapillaris, Sattler's and Haller's layers of the choroid. Use of a 1050 nm light source will provide deep penetration through the retinal pigment epithelium to study changes in vascularization associated with nonexudative AMD, a condition for which there is currently no effective treatment. It will also permit in vivo examination of changes in subretinal vascularization associated with anti-VEGF treatment for neovascular AMD, a treatment that is generally effective but not completely understood. Aim 2 will measure fundus autofluorescence (FAF) and morphology of the retinal pigment epithelium in geographic atrophy using ultrahigh-resolution adaptive optics (AO) with simultaneous reflectance and fluorescent scanning laser ophthalmoscopy and OCT volumetric imaging to co- localize disease-related changes visualized with the two modalities. This aim will investigate the hypothesis that some of the changes in FAF characterizing AMD are secondary to changes in rhodopsin photopigment screening of the excitation and emitted light. This result may alter interpretations of FAF changes in AMD and other diseases of the chorioretinal complex associated with rod photoreceptor losses, and will be critical in developing or assessing new treatments. Aim 3 will use a newly constructed afocal AO-OCT system and phase retrieval algorithm to measure changes in length and renewal rates of the photoreceptor outer segments in normal retinae and those with drusen characteristic of early and intermediate stage AMD. Changes in photoreceptors will be characterized over short- and long-term time scales. These results may provide new and sensitive functional indicators of AMD progression and a leading indicator of changes in the health of the chorioretinal complex at the intersection between biological aging and eye disease.

Tissue Structure and Function: combines two cores from the prior project period. Histology & Phenotyping and Retinal Anatomy & Physiology. It will be- co-directed by Paul FitzGerald and Andrew Ishida who were the directors of the former cores. This core will support anatomy and physiology research of ocular structures and retina with facilities utilized by multiple basic and clinical researchers. There is a strong need for these resources, especially to meet intermittent needs of laboratories that lack the equipment and expertise provided. At the same time, the two former cores are being consolidated to support other pressing needs of our investigators. 13 of our Core-eligible R012 investigators and two new faculty are anticipated to be moderate to extensive users in the next funding period.

Research Plan The University of California at Davis provides a n environment that fosters multidisciplinary research excellence to address fundamental questions on the NEI health and science agendas. UC Davis annually trains the largest number of biological science PhD's in the nation, and is home to one of the nation's fastest growing medical schools, top ranked School of Veterinary Medicine and long recognized College of Biological Sciences. Our campus is geographically the largest of the ten campuses of the UC system, and the National Science Foundation ranks Davis as first among the UCs for funding in the biological sciences. UC Davis is also ranked 6* among all U.S. universities for contributions to society {Washington Monthly, 2010), 4* among U.S. universities in number of international scholars {Open Doors 2008 Report on International Educational Exchange) and is the 17* most racially and ethnically diverse large research university {U.S. News and World Report, 2009). Total enrollment is over 24,750 undergraduates and ~7,553 graduate and professional students, the third largest in the UC System. Partly because of space limitations at most other UC campuses, the Davis campus has been targeted for continued growth. Vision science has been, and is expected to continue to be, a major beneficiary of this growth. This proposal seeks continued funding for the NEI Core grant at UC Davis. Since it was initially funded in 1998, this Core grant has played a critical role in the growth of vision research on our campus, and we anticipate that it will continue to do so in the foreseeable future. Vision science at UC Davis now includes 35 investigators, across 14 departments, each with extensive individual facilities, extramural support, and research programs which collectively cover a broad range of areas including genetics, molecular biology, optics, retinal anatomy and physiology, central mechanism physiology and behavior, computational modeling, and perception. UC Davis has a long history of support for integration across disciplines that is facilitated by large-scale resources for basic and translational research that are available to our vision scientists. Selected examples follow: (1) The Mouse Biology Program makes nearly 200 genetically altered mice strains and more than 5,000 embryonic-stem cell derived knockout strains. Several of our Core investigators (Burns, Glaser, Cheng) use mice from this program. (2) The California National Primate Research Center is one of the largest of the eight NIH-funded regional facilities, housing more than 6,000 nonhuman primates. It supports the research of two Core investigators studying visual cortex (Britten, Usrey). (3) The Center f o r Neuroscience provides laboratory space for 25 faculty members and has made vision science a priority. It houses several Core investigators (Britten, Cheng, Krubitzer, Usrey) and provides dedicated space for the Software Engineering Core. It includes three buildings (55,000 ft 2) containing offices, vivaria and labs for the study of awake behaving monkeys, as well as a newly installed 3T Skyra MRI scanner configured for structural and functional imaging studies of human and non-human primates. (4) The Center for Mind and Brain is a university initiative providing more than 30,000 ft 2 of custom-designed facilities dedicated to investigations of higher-level perception and cognition. One member of this Center (Oakes) has a Core-eligible R01, while two other vision scientists in this Center are supported by NSF and NIMH. (5) The Departments of Ophthalmology in the School of Medicine (SOM) and the School of Veterinary Medicine (SVM) devote considerable resources for vision research. Ophthalmology in the SOM serves as the primary research site for 26 faculty. Administrative support is provided for this Core grant in space adjacent to the Pi's office and laboratories (~2,500 ft 2). Ophthalmology in the SVM has the largest collection of board-certified ophthalmologists in the nation, and includes four faculty, and one NEI KO-8 funded DVM-PhD. Recently renovated research space (~2,400 ft2) contains multiple examination and procedures rooms, and provides shared support for optical and retinal phenotyping of a range of animal species. It is shared with vision scientists outside the SVM. (6) The Clinical and Translational Science Center is one of 12 founding NIH Clinical and Translational Science Centers nationwide that were awarded in 2006. It is housed in a specially renovated, 16,000 ft 2 facility to support collaborations between basic and applied vision scientists. It has supported several projects by clinical vision scientists at UC Davis (Keltner, Lim, Park). (7) The California Institute for Regenerative Cures serves as a hub for basic, translational, and clinical regenerative medicine and includes the UC Davis Stem Cell Program that provides scale-up services for clinical cellular therapy trials to be performed in the Good Manufacturing Practice facility, the only one in Northern California. This facility houses the laboratory of a recently hired NEI Core researcher (Zhao). These resources make UC Davis uniquely poised for continued excellence in the basic sciences and growth in translational research in the vision sciences. The cores proposed here will facilitate this growth.