Biology and therapy of inherited retinal degenerative disease: insights from mouse models

• Published in: Disease models & mechanisms Vol. 8; no. 2; pp. 109 - 129
• Main Authors: Veleri, Shobi, Lazar, Csilla H., Chang, Bo, Sieving, Paul A., Banin, Eyal, Swaroop, Anand
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.02.2015; The Company of Biologists Limited; The Company of Biologists
• Subjects: Animals; Disease; Disease Models, Animal; Genes; Genetic Diseases, Inborn - therapy; Humans; Light Signal Transduction; Macular degeneration; Mice; Mouse mutants; Mutation; Photoreceptor; Photoreceptor Cells, Vertebrate - pathology; Photoreceptors; Proteins; Retina; Retina - pathology; Retina - physiopathology; Retinal Degeneration - therapy; Retinal development; Retinal disease; Review; Retinal development; Mouse mutants; Retinal disease; Photoreceptor
• ISSN: 1754-8403; 1754-8411; 1754-8411
• DOI: 10.1242/dmm.017913

Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.