Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
David Heron - Xavier University of Louisiana
Co-Author(s): Dalia El-Desoky, Kevionta Wilson, Maya White, Chelsi Watson, Ahamed Hossain, and Partha S Bhattacharjee, Xavier University of Louisiana, New Orleans, LA
Vascular changes in the retina are traditionally considered as a classic diagnostic feature of diabetic retinopathy (DR). However, color blindness, lack of contrast sensitivity and abnormal electroretinogram characteristic to retinal neurodegeneration are documented in diabetic patients before clinically evident blood vessel changes arise. In fact, diabetes-induced retinal neurodegeneration precedes vascular damage. Two hallmark features of retinal neurodegeneration are neuronal (retinal ganglionic cell-RGC) apoptosis and Muller cell (only immune cell in the retina) hyperactivity. Critical barriers to the development of adequate therapeutic strategies for the treatment of DR is related to the lack of information about the mechanism of early retinal neurodegeneration and its progression to late vascular abnormalities. Our studies with genetically modified db/db (mimicking human type 2 diabetes mellitus) mouse eye model suggest a signaling pathway involving low-density lipoprotein receptor-related protein-1 (LRP-1) protecting neurons from apoptosis. Our results also suggest that LRP-1 activation prevents neuronal apoptosis in the retina by regulating the PI3k/Akt pro-survival pathway and MAPK/Erk pro-apoptotic pathway. We suggest a new therapeutic strategy of inhibiting neuronal apoptosis in diabetic retina and may benefit the interventional approach against other retinal neurodegenerative diseases such as glaucoma and AMD (age-related macular degeneration).
Funder Acknowledgement(s): Support is provided in part by grant number 2G12MD007595-06 from the National Institute on Minority Health and Health Disparities (NIMHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS) and its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIMHD or NIH.
Faculty Advisor: Partha Bhattacharjee, firstname.lastname@example.org
Role: Immunohistochemistry and assisted in western blotting