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

Bin Wen,Yu Chen,Ling Hou,Fan Lu,Jing Wang,Xiaoyin Ma,Huirong Li,Shuang Li,Jia Qu

doi:10.1038/srep21208

Abstract

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.

Highlights

Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision
Our results show that the visual cycle genes Rlbp[1] and Rdh[5] expression are reduced in the RPE of P11 and optic cups of E12.5 of Mitf mutant mouse embryos, and Rlbp[1] and Rdh5-expression is missing in Mitf mutant embryonic RPE cells
Bruch’s membrane was interrupted and melanosomes and melanin were absent (Fig. 1A–F). These results indicated that the RPE was retained in Mitf− /− mice, its ultrastructure was abnormal

Summary

Introduction

Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. 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, Rlbp[1] which encodes retinaldehyde binding protein-1 (RLBP1), and Rdh[5], which encodes retinol dehydrogenase-5 (RDH5). Prominent among the many functions of the RPE is its role in the visual cycle, a process responsible for reconstituting 11-cis-retinal from all-trans retinol. MITF is a member of the microphthalmia family of transcription factors (MiT) It is expressed at various levels in a variety of cell types, including neural crest-derived melanocytes and RPE cells where it plays prominent roles in development[7,8]. Other Mitf mutant alleles, such as microphthalmia-brownish (MitfMi−b) and www.nature.com/scientificreports/

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