Journal Article

Achromatopsia: Genetics and Gene Therapy

Michalakis, Stylianos, Priglinger, Siegfried, Priglinger, Claudia, Rudolph, Günther, Gerhardt, Maximilian

2022

Overview

Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the retina, the type of photoreceptors responsible for high-acuity daylight vision. ACHM is caused by pathogenic variants in one of six cone photoreceptor-expressed genes. These mutations result in a functional loss and a slow progressive degeneration of cone photoreceptors. The loss of cone photoreceptor function manifests at birth or early in childhood and results in decreased visual acuity, lack of color discrimination, abnormal intolerance to light (photophobia), and rapid involuntary eye movement (nystagmus). Up to 90% of patients with ACHM carry mutations in CNGA3 or CNGB3 , which are the genes encoding the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel, respectively. No authorized therapy for ACHM exists, but research activities have intensified over the past decade and have led to several preclinical gene therapy studies that have shown functional and morphological improvements in animal models of ACHM. These encouraging preclinical data helped advance multiple gene therapy programs for CNGA3 - and CNGB3 -linked ACHM into the clinical phase. Here, we provide an overview of the genetic and molecular basis of ACHM, summarize the gene therapy-related research activities, and provide an outlook for their clinical application.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Acuity / Amino acids / Animal models / Biomedical and Life Sciences / Biomedicine / Blindness / Cancer Research / Children / Color blindness / Color vision / Cones / Degeneration / Eye movements / Gene therapy / Genes / Genetics / Human Genetics / Intolerance / Laboratory Medicine / Molecular Medicine / Morphology / Mutation / Nucleotides / Nystagmus / Pharmacotherapy / Photoreception / Photoreceptors / Proteins / Retina / Retinal degeneration / Review / Review Article / Signal transduction / Visual acuity / Visual discrimination