Role of Photoreceptor Retinol Dehydrogenases in Detoxification of Lipid Oxidation Products

Photoreceptor cells express various retinol dehydrogenase enzymes (RDHs), located either in the outer segment where they reduce all-trans retinal released from opsin in this compartment, or in the inner segment where their function(s) are not completely resolved. In this chapter, we present evidence for a housekeeping detoxification role of RDH12 in photoreceptor inner segments, reducing 4-hydroxynonenal produced by a basal level of lipid oxidation taking place constantly in mouse retina. Loss of this function in patients with inherited retinal dystrophy due to mutations in RDH12 might contribute to the dramatic and early onset loss of vision in these individuals. RDH11 and RDH13 may have redundant or complementary roles in mouse photoreceptor inner segments. Mouse models with disruption of various combinations of these RDHs are expected to help achieve a better understanding of the specific and redundant functions of these enzymes.