This proposal is for completing an ongoing study that aims to determine risk factors for the development of neovascular/exudative (N/E), as well as for atrophic (non-exudative) macular degeneration. Age-related macular degeneration (AMD) is a leading cause of blindness in the United States. About 90% of severe visual loss caused by AMD is due to the N/E form of the disease. Because treatment is available for certain patients with N/E AMD, it is important to identify persons at high risk who can be diagnosed at an early stage of the disease when treatment is most effective. Previous studies have suggested associations of N/E and/or atrophic AMD with factors such as systemic hypertension, cardiovascular disease, and nutritional factors, but the evidence is inconclusive. The completed study will: 1) evaluate the hypothesis that systemic hypertension and cardiovascular disease are related to an increased risk of N/E or atrophic AMD, 2) evaluate the contribution of nutritional status (e.g., Vitamins E, A, C, selenium, and carotene) to the risk of developing N/E or atrophic AMD, and 3) evaluate the contribution of various other factors to the risk of developing N/E or atrophic AMD and determine whether these factors differ among individuals with N/E and atrophic disease. The variables under study include iris color, refractive error, family history of AMD, cigarette smoking, light exposure, and occupational exposures. This information is being obtained by a case-control study consisting of ophthalmology patients aged 50-79 years, who are divided into three groups of similar age and sex consisting of 300 patients each: Group I, newly diagnosed patients with definite N/E AMD, Group II, newly diagnosed patients with definite atrophic AMD, and Group III, control patients without evidence of macular disease. All patients are interviewed and have blood pressure, visual acuity, refractive error, and hand grip measured, fundus and iris photographs taken, and blood drawn for determination of cholesterol, triglycerides, HDL, LDL, and Vitamins E, A, C, selenium, glutathione peroxidase, and carotene. Information on past medical, occupational, dietary , and family history, as well as other factors, is obtained by patient interview. Medical histories are validated by the treating physicians; family histories are validated by contracting family members and their eye examiners. Estimates of the risks involved will be obtained from comparisons of the case groups and controls.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005633-06
Application #
3260896
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-12-01
Project End
1992-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Park, J K; Herron, B J; O'Donnell, J J et al. (1992) Three novel mutations of the ornithine aminotransferase (OAT) gene in gyrate atrophy. Genomics 14:553-4
Ramesh, V; Cheng, S V; Kozak, C A et al. (1992) Mapping of ornithine aminotransferase gene sequences to mouse chromosomes 7, X, and 3. Mamm Genome 3:17-22
Park, J K; O'Donnell, J J; Shih, V E et al. (1992) A 15-bp deletion in exon 5 of the ornithine aminotransferase (OAT) locus associated with gyrate atrophy. Hum Mutat 1:293-7
Ramesh, V; Gusella, J F; Shih, V E (1991) Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency. Mol Biol Med 8:81-93
McClatchey, A I; Kaufman, D L; Berson, E L et al. (1990) Splicing defect at the ornithine aminotransferase (OAT) locus in gyrate atrophy. Am J Hum Genet 47:790-4
Ramesh, V; McClatchey, A I; Ramesh, N et al. (1988) Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and -nonresponsive forms of gyrate atrophy. Proc Natl Acad Sci U S A 85:3777-80
Ramesh, V; Benoit, L A; Crawford, P et al. (1988) The ornithine aminotransferase (OAT) locus: analysis of RFLPs in gyrate atrophy. Am J Hum Genet 42:365-72
Ramesh, V; Eddy, R; Bruns, G A et al. (1987) Localization of the ornithine aminotransferase gene and related sequences on two human chromosomes. Hum Genet 76:121-6
Ramesh, V; Shaffer, M M; Allaire, J M et al. (1986) Investigation of gyrate atrophy using a cDNA clone for human ornithine aminotransferase. DNA 5:493-501