1985 — 2007 |
Berson, Eliot 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. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Electrophysiological Studies of Retinal Degenerations @ Harvard University (Medical School)
DESCRIPTION (provided by applicant): Retinitis pigmentosa is a group of hereditary retinal diseases that often lead to blindness; an estimated 50,000 to 100,000 people are affected in the United States. More than 10,000 patients are on file in this research center. Considerable progress has been made in defining the gene defects that cause these conditions, but the course of disease for most subgroups is not known. We propose to mode the course of disease based on data from our large number of patients with multiple visits and up to 32 years of follow-up. We will then use the optimal model as a template to define the rates of progression in patients with two relatively common subgroups of retinitis pigmentosa caused by USH2A or RPGR mutations, respectively. Rates of progression will be monitored with respect to visual acuity, visual field area and sensitivity, and full-field electroretinogram amplitude. We will perform genotype/phenotype correlations to see if rates of progression can be related to category of mutation. These data should provide guidelines for estimating long-term visual prognoses in patients with USH2A or RPGR mutations and provide a framework for considering gene-specific therapies that may arise in the future for these patients. We also propose to compare the course of disease in affected sibpairs, regardless of mutation, to facilitate identification of nutritional and other non-genetic factors that may affect rates of progression. Information derived from this research could reveal factors that are associated with a slower or faster course of disease with potential implications for therapy. We will also continue genotype/phenotype correlations in patients with newly defined gene defects.
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0.958 |
1985 — 1993 |
Berson, Eliot L |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. U01Activity 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. U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Studies of Retinitis Pigmentosa and Allied Diseases @ Harvard University (Medical School)
This specialized research center with more than 2,000 patients on file with retinitis pigmentosa and allied retinal degenerations proposes to continue studies on the course of these diseases as monitored with psychophysical and electroretinographic testing. Research is also planned to study postmortem donor eyes with these diseases with morphometric and biochemical analyses as well as tissue culture techniques to help define pathogenetic mechanisms. Attention will be given to evaluating in postmortem donor eyes those abnormalities known or thought to play a role in the pathogenesis of photoreceptor cell death in animal models of retinal degenerations. Data derived from clinical and laboratory studies will be evaluated with biostatistical methods to better define the course, region-specific changes in donor eyes, and possible effect modifiers. The hope is that this research will reveal pathogenetic mechanisms and thereby increase understanding of this group of diseases which affect an estimated 50,000 to 100,000 people in this country and countless others around the world.
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0.958 |
1987 — 1991 |
Berson, Eliot 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. |
Retinal Electrophysiological Studies @ Harvard University (Medical School)
Thousands of patients including many young children become blind from retinitis pigmentosa and allied diseases. No treatments are known for practically all types. Research is proposed to gain more understanding of the pathogenesis of these diseases through assessing the diurnal rhythm in the rod electroretinogram (ERG) as a measure of rod outer segment renewal in patients with different stages and genetic types of these diseases and in normal subjects. In addition, rod ERGs measured at various times of the day will be used to determine whether or not an abnormal diurnal rhythm exists in the miniature French poodle with rod-cone degeneration and in the Royal College of Surgeons rat with hereditary retinal degeneration at various stages of rod degeneration. Results will be compared with observations on the diurnal rhythm of normal French poodles and normal rats. At corresponding times in the diurnal cycle, ERGs from the normal rats and poodles will be compared with histologic observations of outer segment length and of numbers of phagosomes in the pigment epithelium. The natural history of retinal malfunction in the miniature French poodle with rod-cone degeneration will also be monitored with electrophysiological testing; waveforms obtained at different stages will be compared with responses obtained from humans with hereditary retinal diseases. Electroretinographic testing and histologic studies will be done in the isolated cat eye perfused with pharmacologic agents thought to lead to photoreceptor and/or pigment epithelial cell death in hereditary retinal degenerations; attention will be given to whether or not these agents produce abnormal ERGs similar to those seen in human hereditary retinal degenerations. Electroretinographic studies of patients with retinitis pigmentosa will also be done to determine if delays in cone b-waves implicit time under light-adapted conditions, characteristic of progressive forms of these diseases, are secondary to abnormal rod-cone interaction and/or delays in cones a-wave latency. Obligate female carriers of sex-linked choroideremia will be evaluated with the ERG to determine to what extent the ERG can be used to detect carriers of this condition.
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0.958 |
1992 |
Berson, Eliot L |
U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Retinitis Pigmentosa and Allied Diseases @ Harvard University (Medical School)
This specialized research center with more than 2,000 patients on file with retinitis pigmentosa and allied retinal degenerations proposes to continue studies on the course of these diseases as monitored with psychophysical and electroretinographic testing. Research is also planned to study postmortem donor eyes with these diseases with morphometric and biochemical analyses as well as tissue culture techniques to help define pathogenetic mechanisms. Attention will be given to evaluating in postmortem donor eyes those abnormalities known or thought to play a role in the pathogenesis of photoreceptor cell death in animal models of retinal degenerations. Data derived from clinical and laboratory studies will be evaluated with biostatistical methods to better define the course, region-specific changes in donor eyes, and possible effect modifiers. The hope is that this research will reveal pathogenetic mechanisms and thereby increase understanding of this group of diseases which affect an estimated 50,000 to 100,000 people in this country and countless others around the world.
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0.958 |
1995 — 2001 |
Berson, Eliot L |
U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Randomized Trial For Retinitis Pigmentosa @ Harvard University (Medical School) |
0.958 |
2002 — 2008 |
Berson, Eliot L |
U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Randomized Clinical Trial For Retinitis Pigmentosa @ Harvard University (Medical School)
This specialized research center with more than 10,000 patients on file with retinitis pigmentosa proposes a clinical trial to determine whether a nutritional supplement will slow the course of the common forms of retinitis pigmentosa. Two hundred and eleven patients who meet a preset list of eligibility criteria will be randomly assigned to either a treatment or a control group and followed annually over a period of 5 years. All patients will receive 15,000 IU/day of vitamin A palmitate. Static perimetric thresholds measured with a Humphrey Field Analyzer will be used as the primary outcome measure. Electroretinograms, visual acuities, and assessment of quality of life will be monitored as secondary outcome measures. The study will be conducted with a double-masked protocol. Collaborative arrangements have been made for biochemical analyses with Tufts University School of Medicine and Brandeis University.
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0.958 |