Let There Be Light: Gene and Cell Therapy for Blindness

Abstract

Retinal degenerative diseases are a leading cause of irreversible blindness. Retinal cell death is the main cause of vision loss in genetic disorders such as retinitis pigmentosa, Stargardt disease, and Leber congenital amaurosis, as well as in complex age-related diseases such as age-related macular degeneration. For these blinding conditions, gene and cell therapy approaches offer therapeutic intervention at various disease stages. The present review outlines advances in therapies for retinal degenerative disease, focusing on the progress and challenges in the development and clinical translation of gene and cell therapies. A significant body of preclinical evidence and initial clinical results pave the way for further development of these cutting edge treatments for patients with retinal degenerative disorders.

Figure 1.

Progression of a genetic disease through retinal cell death: autosomal dominant retinitis pigmentosa serves as an example. Healthy retina is composed of five neuronal types, with the photoreceptors being the primary neurons. In retinitis pigmentosa, mutations mostly in rod transcripts (shown in blue) lead to degeneration of these cells (stage I) followed by progressive cone (orange) degeneration (stages II and III). In the final stage (stage IV), all photoreceptor cells are lost, leaving the retina blind. Color images available online at www.liebertpub.com/hum