Targeting the Body’s Natural Defense Mechanism as an Atrophic AMD Therapy
Detailed Non-Technical Summary
We have shown that Akt2 activation in the RPE drives retinal inflammation and degeneration in a mouse model and in human dry AMD. The study is innovative as; (i) We have generated two unique animal models (RPE-specific Best1-Akt2 KI mice overexpressing Akt2 and Akt2 cKO mice, lacking a functional Akt2 gene) to understand AMD-like inflammatory signaling cascades. (ii) For the first time, we will evaluate (a) how Akt2 activation in the RPE triggers retinal inflammation and (b) how the dynamic interaction between infiltrating neutrophils and retinal microglia contributes to retinal degeneration. Atrophic/dry AMD is the leading cause of blindness in the elderly and is driven by multiple genetic and environmental factors, for which there are no definitive treatment options available at present. We believe that our work may provide novel background information for future drug development for combatting retinal inflammation and degeneration in dry AMD.