RDH5

RDH5, or retinol dehydrogenase 5, also known as 11-cis-retinol dehydrogenase, is a member of the short-chain dehydrogenase/reductase (SDR) family encoded by the RDH5 gene in humans. The enzyme is expressed predominantly in the retinal pigment epithelium and to a lesser extent in photoreceptors, where it participates in the vertebrate visual cycle.

In the visual cycle, RDH5 catalyzes the NADPH-dependent oxidation of 11-cis-retinol to 11-cis-retinal, a critical chromophore that binds opsin to form visual pigments such as rhodopsin. This step follows the isomerization of retinoids by RPE65 and is necessary to regenerate functional photopigments after light exposure.

Mutations in RDH5 cause autosomal recessive retinal disorders, most notably fundus albipunctatus, characterized by delayed dark adaptation and distinctive white dot fundus lesions; some patients present with night blindness in adolescence or adulthood. The phenotype can range from isolated night vision difficulties to more extensive retinopathy.

Biochemically, RDH5 is an SDR enzyme with conserved catalytic tyrosine and lysine and a cofactor-binding motif typical of the family. It uses NADPH as a cofactor to oxidize substrates. The enzyme's activity can be studied in vitro with retinal tissues and cell models.

Animal models, such as RDH5-deficient mice, show disrupted 11-cis-retinal production and delayed or incomplete recovery of visual sensitivity after dark adaptation, supporting its role in the visual cycle. Therapeutic approaches under study include gene therapy and pharmacological strategies to restore retinoid balance.