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Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. Here we show that the microphthalmia-associated transcription factor, MITF, which plays a central role in the development and function of RPE cells, regulates the expression of two visual cycle genes,  Rlbp1  which encodes retinaldehyde binding protein-1 (RLBP1), and  Rdh5 , which encodes retinol dehydrogenase-5 (RDH5). First, we found that  Rlbp1  and  Rdh5  are downregulated in optic cups and presumptive RPEs of  Mitf -deficient mouse embryos. Second, experimental manipulation of MITF levels in human RPE cells in culture leads to corresponding modulations of the endogenous levels of RLBP1 and RDH5. Third, the retinal degeneration associated with the disruption of the visual cycle in  Mitf -deficient mice can be partially corrected both structurally and functionally by an exogenous supply of 9-cis-retinal. We conclude that the expression of  Rlbp1  and  Rdh5  critically depends on functional  Mitf  in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE.

Microphthalmia-associated transcription factor regulates the visual cycle genes Rlbp1 and Rdh5 in the retinal pigment epithelium