Homocysteine's role in the causation of presbyopia
Principal Investigator: Charles W Prince
Abstract: Elevated circulating homocysteine is the major biochemical feature of cystathionine beta-synthase deficiency (also known as homocystinuria) with total plasma levels usually exceeding 100microM (normal total plasma levels do not exceed 100microM. It is clear from the set of pathologies that occurs in this disorder that severe hyperhomocysteinemia has significant detrimental effects on connective tissues- the most commonly observed pathological changes related to the eye are ectopia lentis preceded by presbyopia and severe myopia. We propose the hypothesis that mild to moderate hyperhomocysteinemia is a risk factor for presbyopia. We shall correlate measured accommodative amplitude with total Hcy (tHcy) levels in plasma (an inverse correlation is expected), and with the distribution of a major genetic polymorphism (5,10-methylenetera-hydrofolate reductase (MTHFR), C677T, Ala > VaI) known to be associated with elevated tHcy. We expect to find the abnormal genetic trait more prevalent among individuals with low accommodative amplitude. In this Pilot Project, we therefore propose three specific aims designed to provide preliminary data supportive of an R01 application. Specific Aim 1. To recruit at least 30 subjects of each MTHFR genotype (homozygous normal, heterozygote, homozygous mutant), aged 20 to 39 years, and measure their accommodative amplitude in one eye. Specific Aim 2: For subjects for whom the following data are not already available, to: a) determine total plasma levels of homocysteine (tHcy), folate and vitamin B12; b) establish the genotype of the participants with regard to the thermolabile variant of MTHFR; and c0 archive of -70 degrees Centigrade the DNA and plasma samples for future extension of these studies. Specific Aim 3. To statistically analyze the results correlating accommodative amplitude to tHcy. MTHFR genotype and blood folate and vitamin B12 levels; to undertake multivariate analysis using the linear regression model to assess the effect of tHcy on accommodation amplitude while adjusting for age, MTHFR status, folate, and vitamin B12 levels. Estimates of regression coefficients and tests of significance will be based on t-test and F-test statistics.
Funding Period: 2002-08-01 - 2005-07-31
more information: NIH RePORT
- C677T methylene-H4-folate-reductase variant decreases binocular accommodationCarlos L Krumdieck
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Optom Vis Sci 85:196-200. 2008..In this study we examined 100 apparently normal subjects of both sexes (average age 25.6 +/- 4.25) for the genotypic presence of the T allele and its association with accommodative amplitude (AA)...