Livia S. Carvalho and Luk H. Vandenberghe
Abstract
Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.

Keywords

Achromatopsia · Cone dystrophies · Cone photoreceptors · Cell death · Cone degeneration · Apoptosis

München, Munich, Germany *Correspondence should be addressed to: Dr. Stylianos Michalakis, Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr 5-13, D-81377 Munich, Germany, Phone: +49 (0) 89 218077325, Fax: +49 (0) 89 218077326, Email: stylianos.michalakis@cup.uni-muenchen.de Keywords: adeno-associated virus (AAV), gene - therapy, neuroscience, vector – viral, animal model, clinical research Running Title: ACHM Gene Therapy
Abstract
Aim This review summarizes the current status of Achromatopsia (ACHM) gene therapy-related research activities and provides an outlook for their clinical application. Discussion ACHM is an inherited eye disease characterized by congenital absence of cone photoreceptor function. As a consequence, ACHM is associated with strongly impaired This article is protected by copyright. All rights reserved. daylight vision, photophobia, nystagmus, and lack of color discrimination. Currently, six genes have been linked to ACHM. Up to 80% of the patients carry mutations in the genes CNGA3 and CNGB3 encoding the two subunits of the cone cyclic nucleotide-gated (CNG) channel. Various animal models of the disease have been established and their characterization helped to increase our understanding of the pathophysiology associated with ACHM. With the advent of adeno-associated virus (AAV) vectors as valuable gene delivery tools for retinal photoreceptors a number of promising gene supplementation therapy programs have been initiated.