Catherine Tsilfidis

Retinal diseases, retinal gene therapy, apoptosis of retinal cells as a cause for retinal disease, anti-apoptotic strategies for preserving retinal cells and delaying retinal disease progression

Inherited retinal degenerations lead to a progressive loss of vision. Most often, they are characterized by a gradual loss of the photoreceptors in the retina. Cell death occurs through the process of apoptosis. We believe that regardless of the genetic mutation which a cell possesses, if we can target and prevent the ultimate death of the cell, we will be able to retain function in the retina and prevent vision loss. We are using inhibitors of apoptosis (IAPs) to try to prevent the retinal degeneration which is associated with diseases such as retinitis pigmentosa, retina&nbspischemia, or Leber's Hereditary Optic Neuropathy (LHON). The X-linked inhibitor of apoptosis (XIAP) protein prevents apoptosis by blocking the action of caspases, which are enzymes that are involved in the cell death pathway. Delivery of XIAP to the retina using adeno-associated virus results in efficient infection of retinal cells and leads to over-expression of XIAP in the target cells. We have used this approach to show that XIAP protects photoreceptors in animal models of chemotoxic damage, retinal ischemia, and retinitis pigmentosa. Our current studies are aimed at developing this therapeutic strategy for application to human retinal disease.