PHOTORECEPTOR RETINOL DEHYDROGENASES AND VISION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Retinol Dehydrogenases RDH11 and RDH12 are closely related microsomal oxidoreductases located in photoreceptor inner segments. Mutations in the human RDH12 gene induce the most severe and early onset type of inherited retinal degeneration, called Leber Congenital Amaurosis Type 3 (LCA3). We are investigating the function of this enzyme and the molecular mechanisms leading to vision loss and photoreceptor cell death in RDH12-induced LCA. We are specifically interested by the detoxification role of RDH12, and of other retinol dehydrogenases such as RDH11, RDH13, and DHRS3, all located in photoreceptor cells, in different subcellular compartments. We have recently discovered that RDH12 can detoxify damaging aldehydes produced by lipid peroxidation in photoreceptor cells. Such endogenous protection might be necessary to maintain the functional integrity of photoreceptor cells. This hypothesis predicts that photoreceptors die in LCA3 patients due to an absence of this detoxification activity.