34] Animal models of inherited retinal diseases

Abstract

This chapter summarizes vertebrate animal models of retinal degeneration consisting of two groups: the naturally occurring, and the laboratory generated. Of several hundred inherited diseases affecting the human eye or the retina, relatively few have been characterized at a molecular genetic level. Among these, retinitis pigmentosa (RP), a large and heterogeneous group of blinding disorders, has been studied intensively at the molecular level. Particularly useful in determining biochemical mechanisms has been animal models of hereditary degeneration that simulate human diseases. Naturally occurring mutations affect a variety of genes, including genes involved in phototransduction (rd mouse, rd chicken), genes encoding structural proteins of photoreceptors (rds mouse), genes encoding transcription factors (vitiligo), or genes also expressed in other tissues (shaker mouse). Laboratory-generated mutants consist typically of transgenic mice or mice in which a gene of interest has been knocked out. Other vertebrate animals, for example, Xenopus and zebrafish, are used increasingly to generate animal models. Genes targeted include those involved in photoreception (rhodopsin), phototransduction (cGMP cascade), the visual cycle, cellular metabolism (transporters, channels, enzymes), cell structure (cytoskeleton, membrane components), or genes involved in development (transcription factors).