Rdh12, or retinol dehydrogenase 12, is an NADPH-dependent retinal reductase expressed in photoreceptor inner segments. It is part of the visual cycle, crucial for visual pigment regeneration, and may also be involved in detoxifying lipid peroxidation products [1].

Gene-knockout (KO) mouse models of Rdh12 have provided some insights. Although they do not fully recapitulate the severe phenotypes seen in patients with Rdh12-related diseases, studies on these models have shown that Rdh12-deficiency can lead to visual dysfunction and photoreceptor degeneration, similar to what is observed in Rdh12-associated inherited retinal diseases (Rdh12-IRD) patients. Preventive gene therapy in Rdh12 -/- mice can maintain normal visual function and prevent photoreceptor loss, while salvage gene therapy can slow down the loss of visual function [3]. Additionally, Rdh12 -/- mice also exhibit significant alterations in serum uric acid levels and kidney-related biochemical indicators, along with mild renal pathological lesions, suggesting a role of Rdh12 mutations in contributing to hyperuricemia and renal disease phenotypes in mice [2].

In summary, Rdh12 is essential for the visual cycle and plays a significant role in maintaining normal retinal function. Mouse models, especially Rdh12 KO models, have been valuable in revealing its role in retinal diseases and other potential disease areas such as hyperuricemia and renal diseases. Understanding Rdh12's functions through these models provides a basis for developing therapeutic strategies for related diseases.

References:

1. Sarkar, Hajrah, Moosajee, Mariya. 2019. Retinol dehydrogenase 12 (RDH12): Role in vision, retinal disease and future perspectives. In Experimental eye research, 188, 107793. doi:10.1016/j.exer.2019.107793. https://pubmed.ncbi.nlm.nih.gov/31505163/

2. Bian, Jiaxin, Chen, Hongyu, Sun, Junhui, Qi, Ming, Pan, Qing. 2024. Retinol dehydrogenase 12 (RDH12) knock out may cause hyperuricemia phenotype in mice. In Biochemical and biophysical research communications, 709, 149809. doi:10.1016/j.bbrc.2024.149809. https://pubmed.ncbi.nlm.nih.gov/38552555/

3. Bian, Jiaxin, Chen, Hongyu, Sun, Junhui, Pan, Qing, Qi, Ming. 2021. Gene Therapy for Rdh12-Associated Retinal Diseases Helps to Delay Retinal Degeneration and Vision Loss. In Drug design, development and therapy, 15, 3581-3591. doi:10.2147/DDDT.S305378. https://pubmed.ncbi.nlm.nih.gov/34429587/