Retina-Seal: Gene therapy mediated regulation of the blood retina barrier

Introduction

Age-related macular degeneration (AMD) is the leading cause of irreversible central blindness in the world. The number of people with AMD is predicted to be 288 million by 2040, with an estimated 1 in 10 people over the age of 55 already showing early signs of the condition.

Background

At the inner blood retina barrier (iBRB), claudin-5 is the most enriched component of the tight junctions of endothelial cells, regulating the paracellular diffusion of molecules into and out of the retina.

Research Context

As part of the ongoing ERC Consolidator grant Retina-Rhythm, we now have a very large body of data suggesting that “leaky” or “CLDN-5 depleted” retinal vasculature drives the accumulation of waste material known as drusen, the hallmark diagnostic feature of AMD.

Objectives

Therefore, methods aimed at enhancing CLDN-5 expression can potentially stabilize vascular integrity and prevent the onset of AMD (both dry and wet AMD).

Methodology

Here, we will develop novel adeno-associated viruses (AAV) that will directly regulate the expression of two novel target genes and effectively "seal" the blood retina barrier and stabilize disease progression.