Animal models of retinal disease

Abstract

Diseases of the retina are the leading causes of blindness in the industrialized world. The recognition that animals develop retinal diseases with similar traits to humans has led to not only a dramatic improvement in our understanding of the pathogenesis of retinal disease but also provided a means for testing possible treatment regimes and successful gene therapy trials. With the advent of genetic and molecular biological tools, the association between specific gene mutations and retinal signs has been made. Animals carrying natural mutations usually in one gene now provide well-established models for a host of inherited retinal diseases, including retinitis pigmentosa, Leber congenital amaurosis, inherited macular degeneration, and optic nerve diseases. In addition, the development of transgenic technologies has provided a means by which to study the effects of these and novel induced mutations on retinal structure and function. Despite these advances, there is a paucity of suitable animal models for complex diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, largely because these diseases are not caused by single gene defects, but involve complex genetics and/or exacerbation through environmental factors, epigenetic, or other modes of genetic influence. In this review, we outline in detail the available animal models for inherited retinal diseases and how this information has furthered our understanding of retinal diseases. We also examine how transgenic technologies have helped to develop our understanding of the role of isolated genes or pathways in complex diseases like AMD, diabetes, and glaucoma.