SUMMARY OF RESEARCH DURING 2012
(3MD's/PhD's, 13 MD’s; 9 PhD’s; 2 other; 40 publications; 3 book chapters distributed in 2 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.
Area 1: The effects of age and topographic location on gene expression in human neural retina.
- Research: Researchers are studying the temporal and spatial effects on gene expression levels in the retina as some retinal diseases such as age-related macular degeneration (AMD) are age-dependent and affect anatomic regions differently.
- Results: Highly-expressed genes in macular, peripheral, young, or old retina were identified, including genes that are responsible for regulating the Wnt signaling-pathway. A potential strategy for cell replacement in retinal disorders is to activate this pathway in the retina.
- Significance: Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related retinal diseases.
Area 2: The mechanism of the outer blood-retina barrier breakdown
- Research: Researchers are investigating how endogenous and environmental factors influence retinal pigment epithelium (RPE) function, and contribute to the development and resolution of excess retinal fluid which is a common element in several retinal diseases such as diabetic retinopathy and AMD.
- Results: Studies focused on the ability of several proteins called natriuretic peptides to reverse blood-retina barrier dysfunction. Researchers found that these natriuretic peptides suppressed the reduction of RPE barrier function caused by advanced glycation end-products (AGE).
- Significance: By studying the factors that influence RPE function and homeostasis, researchers can identify potential candidates for treating retinal edema in diabetic patients.
Area 3: Alternative pathway of complement activation in AMD
- Research: The goal of this study is to understand how misregulation of complement-signaling in the eye leads to pathology, by looking at downstream effects on secretion and activation of proteolytic enzymes like matrix metalloproteinases (MMPs) in the RPE.
- Results: Results suggest that complement activation alters MMP expression and activation, and has the ability to generate a proangiogenic environment by altering the balance between VEGF and PEDF. Our findings link reported results associated with AMD pathogenesis.
- Significance: A greater understanding of complement-signaling will ultimately aid in the development of therapeutic approaches for devastating retinal diseases.