SUMMARY OF RESEARCH DURING 2009
(19 MD’s; 9 PhD’s; 3 other; 37 publications; 2 books and 26 book chapters distributed in 10 books) Significant Scientific Accomplishments
We continue to expand our understanding of how interactions between retinal metabolism, environmental stress and genetic mutations lead to blindness through 3 major research areas. Age-Related Macular Degeneration (AMD) is being reviewed using high- resolution mapping of lipofuscin components in human eyes. Through matrix-assisted laser desorpiton ionization tissue-imagining, we are determining the abundance and distribution of toxic compounds that accumulate in the retina and their relationship to vision loss in AMD. The accumulation of lipofuscin in the retina is thought to be a central event in the development of AMD. however, lipofuscin is a complex mixture of compounds Understanding the chemical composition of lipofuscin, its rate of accumulation, and geographic distribution of specific components are necessary to understand the pathogenesis of AMD and development of effective treatment of the blinding disease. - Retinal Edema is being studied to determine the contribution of oxidative stress to edema development. We have identified two pathways: first, by enhancing the secretion of proteins that increase the permeability of the retinal pigment epithelium; and second, by suppressing the activity of enzyme systems which normally oppose the actions of these permeability factors. Accumulation of fluid within the retina is a common element associated with vision loss in several diseases. Understanding the events that contribute to these processes and identifying new treatments will improve the quality of life for people suffering from diseases such as diabetic retinopathy and uveitis.
Ischemic Retinal Degeneration is under review to determine if altering protein acetylation can reduce retinal ischemic injury. These studies have provided the first evidence that treatment with histone deacetylase inhibitors and the resulting increase in retinal protein acetylation protects the retina from acute ischemic injury. This response is related to the modulation of transcriptional and inflammatory events within the ischemic retina. Retinal ischemia plays a central role in a number of retinal degenerative diseases such as diabetic retinopathy, glaucoma, and retinal artery occlusion. The use of histone deacetylase inhibitors may provide a novel treatment for preserving vision in these individuals.
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