Mark Kleinman, MD, has been awarded a $2.6 million, 5-year R01 titled “Histone Expression in the Aging RPE”to study histone expression in retinal pigment epithelium (RPE).The awarding agency is the National Instititues of Health National Eye Institute.
Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the world. The scientific understanding of the aging retinal pigment epithelium and molecular mechanisms that trigger AMD progression and RPE cell death are critical to discovering potential therapeutic targets for this blinding disease. Dr. Kleinman, his team, and collaborators will work to define signatures of histone expression in the aging RPE and determine the cellular effects of loss of histone expression in RPE homeostasis and AMD progression. He hypothesizes that histone depletion may be a key factor contributing to RPE aging and senescence, and therapeutic targeting of key histone regulatory mechanisms may serve as a valuable approach to reverse aging and senescence in the RPE.
Dr. Kleinman says, “This will be the first scientific investigation to analyze histone expression signatures in the aging retina with cutting-edge molecular techniques including transcriptomics, proteomics, and epigenomics. Our lab will be working with world-class collaborators at Vanderbilt, University of Illinois, and University of Southern California in a teams-based approach to perform this work. These foundational data will then be utilized to examine the efficacy of stabilizing histone expression profiles and epigenetic marks in novel experimental models to reverse cellular aging in the human retina.”
Dr. Kleinman is a professor in the Department of Surgery and is a local award-winning vitreoretinal specialist and surgeon. He co-discovered the role of specific inflammatory mediators in the progression of dry and wet AMD. This technology has since been licensed and is currently in clinical trials.He is a member of the Center of Excellence in Inflammation, Infectious Disease, and Immunity. Please join us in congratulating Dr. Kleinman on his new R01 grant.
This graphical abstract describes the changes in histone expression in retinal pigment epithelium which is the focus of Dr. Kleinman’s R01 grant. It originally appeared on the May, 2024, cover of Aging Cell in which Dr. Kleinman was the corresponding author for the article “Histone deficiency and hypoacetylation in the aging retinal pigment epithelium.”