Online Issues

Journal Vol 50 (2)

<< All Back-issues

<< This Issue's Table of Contents

AAV-Mediated Gene Therapy for Retinal Disorders in Large Animal Models

Knut Stieger, Elsa Lhériteau, Philippe Moullier, and Fabienne Rolling

Knut Stieger, DVM, PhD, is postdoctoral fellow in the Department of Ophthalmology at Justus-Liebig-University in Giessen, Germany; Elsa Lhériteau is a PhD student, Philippe Moullier, MD, PhD, is Director, and Fabienne Rolling, PhD, is a principal investigator, all at the INSERM U649 Laboratory in Nantes, France.

Address correspondence and reprint requests to Dr. Fabienne Rolling, Laboratoire de Thérapie Génique, INSERM U649, CHU Hôtel-Dieu, Bâtiment J. Monnet, 30 Avenue J. Monnet, 44035 Nantes cedex 01, France or email fabienne.rolling@univ-nantes.fr.

Abstract

Retinal gene therapy holds great promise for the treatment of inherited and noninherited blinding diseases such as retinitis pigmentosa and age-related macular degeneration. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV) because they elicit minimal immune responses and mediated long-term transgene expression in a variety of retinal cell types. Extensive preclinical evaluation of new strategies in large animal models is key to the development of successful gene-based therapies for the retina. Because of differences in the retinal structures among species and unique structures such as the macula and fovea in the primate retina, nonhuman primates are widely used as preclinical animal models. But the observation of inherited retinal degenerations in dogs, which share a number of clinical and pathologic similarities with humans, has led to the characterization of several canine models for retinal diseases, one of which has already responded successfully to AAV-mediated gene therapy. This article presents a review and detailed discussion of the various large animal models available for the study of AAV-mediated gene-based therapies in the retina.

Key Words: adeno-associated virus (AAV); dog model; gene therapy; nonhuman primate; retinal disorders