Retinol dehydrogenase 12 (RDH12) (RDH12)

Retinol dehydrogenase 12 (RDH12) is an NADPH-dependent enzyme primarily localized in the inner segments of photoreceptor cells in the retina (UniProt Q96NR8). It plays a vital role in the visual cycle by catalyzing the reduction of all-trans-retinal to all-trans-retinol, a process essential for the regeneration of visual pigments and the prevention of toxic aldehyde accumulation (PubMed: 15865448). Additionally, RDH12 contributes to the detoxification of lipid peroxidation products, such as 4-hydroxynonenal, protecting the retina from oxidative stress and light-induced damage (PubMed: 19686838). Mutations in the RDH12 gene are a significant cause of Leber Congenital Amaurosis (LCA13) and other severe inherited retinal dystrophies, which typically manifest as early-onset, progressive vision loss leading to legal blindness (NIH: Gene ID 145226). Current therapeutic development focuses on gene supplementation therapies, such as ATSN-201 and OPGx-002, which aim to restore functional enzyme levels in the photoreceptors (Astellas; Opus Genetics). Challenges in drug development include the severe and rapid nature of the retinal degeneration and the difficulty of modeling the human disease in knockout mice, which do not exhibit the same level of photoreceptor loss (PubMed: 31505163).

Other names

SDR7C2LCA13RP53Short-chain dehydrogenase/reductase family 7C member 2All-trans and 9-cis retinol dehydrogenaseRetinol dehydrogenase 12 (all-trans/9-cis/11-cis)

Gene supplementation to restore functional enzyme activity; small molecule modulation of enzyme activity to clear toxic retinoids.