{Reference Type}: Journal Article
{Title}: End binding-3 inhibitor activates regenerative program in age-related macular degeneration.
{Author}: Lee Q;Chan WC;Qu X;Sun Y;Abdelkarim H;Le J;Saqib U;Sun MY;Kruse K;Banerjee A;Hitchinson B;Geyer M;Huang F;Guaiquil V;Mutso AA;Sanders M;Rosenblatt MI;Maienschein-Cline M;Lawrence MS;Gaponenko V;Malik AB;Komarova YA;
{Journal}: Cell Rep Med
{Volume}: 4
{Issue}: 10
{Year}: 2023 10 17
{Factor}: 16.988
{DOI}: 10.1016/j.xcrm.2023.101223
{Abstract}: Wet age-related macular degeneration (AMD), characterized by leaky neovessels emanating from the choroid, is a main cause of blindness. As current treatments for wet AMD require regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) biologics, there is a need for the development of less invasive treatments. Here, we designed an allosteric inhibitor of end binding-3 (EB3) protein, termed EBIN, which reduces the effects of environmental stresses on endothelial cells by limiting pathological calcium signaling. Delivery of EBIN via eye drops in mouse and non-human primate (NHP) models of wet AMD prevents both neovascular leakage and choroidal neovascularization. EBIN reverses the epigenetic changes induced by environmental stresses, allowing an activation of a regenerative program within metabolic-active endothelial cells comprising choroidal neovascularization (CNV) lesions. These results suggest the therapeutic potential of EBIN in preventing the degenerative processes underlying wet AMD.