Rescue of the Congenital Hereditary Endothelial Dystrophy Mouse Model by Adeno-Associated Virus–Mediated Slc4a11 Replacement
Rajalekshmy Shyam, Diego G. Ogando, Edward T. Kim, Subashree Murugan, Moonjung Choi, Joseph A. Bonanno
Abstract
Purpose: CHED mouse model can reverse the disease-associated phenotypes. Design: Experimental study. Participants: mice were administered anterior chamber injections of adeno-associated virus (AAV). Methods: or AAV9-Null vectors. Corneal thickness was measured using OCT. End point analysis included corneal endothelial cell density, mitochondrial oxidative stress, and corneal lactate concentration. Main Outcome Measures: Corneal thickness, endothelial cell loss, lactate levels, and mitochondrial oxidative stress. Results: reversed corneal edema, endothelial cell loss, mitochondrial oxidative stress, lactate transporter expression, and corneal lactate concentration to the levels observed in wild-type animals. In the older animals, gene replacement did not reverse the phenotype but prevented progression. Conclusions: mouse is possible; however, early intervention is critical.