Microphthalmia-associated Transcription Factor Regulates the Visual Cycle Genes Rlbp1 and Rdh5 in the Retinal Pigment Epithelium

Overview

Journal Sci Rep

Specialty Science

Date 2016 Feb 16

PMID 26876013

Citations 23

Authors

Bin Wen

Shuang Li

Huirong Li

Yu Chen

Xiaoyin Ma

Jing Wang

Fan Lu

Jia Qu

Ling Hou

Affiliations

Soon will be listed here.

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.

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References

Thompson D, Li Y, McHenry C, Carlson T, Ding X, Sieving P . Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy. Nat Genet. 2001; 28(2):123-4. DOI: 10.1038/88828. View

Arnheiter H . The discovery of the microphthalmia locus and its gene, Mitf. Pigment Cell Melanoma Res. 2010; 23(6):729-35. PMC: 2964399. DOI: 10.1111/j.1755-148X.2010.00759.x. View

Anderson M, Smith R, Hawes N, Zabaleta A, Chang B, Wiggs J . Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nat Genet. 2001; 30(1):81-5. DOI: 10.1038/ng794. View

Loftus S, Larson D, Baxter L, Antonellis A, Chen Y, Wu X . Mutation of melanosome protein RAB38 in chocolate mice. Proc Natl Acad Sci U S A. 2002; 99(7):4471-6. PMC: 123672. DOI: 10.1073/pnas.072087599. View

Thompson D, Gal A . Vitamin A metabolism in the retinal pigment epithelium: genes, mutations, and diseases. Prog Retin Eye Res. 2003; 22(5):683-703. DOI: 10.1016/s1350-9462(03)00051-x. View

Baxter L, Pavan W . Pmel17 expression is Mitf-dependent and reveals cranial melanoblast migration during murine development. Gene Expr Patterns. 2003; 3(6):703-7. DOI: 10.1016/j.modgep.2003.07.002. View

Spritz R, Strunk K, Giebel L, King R . Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. N Engl J Med. 1990; 322(24):1724-8. DOI: 10.1056/NEJM199006143222407. View

Smith S . C57BL/6J-vit/vit mouse model of retinal degeneration: light microscopic analysis and evaluation of rhodopsin levels. Exp Eye Res. 1992; 55(6):903-10. DOI: 10.1016/0014-4835(92)90017-m. View

Hodgkinson C, Moore K, Nakayama A, Steingrimsson E, Copeland N, Jenkins N . Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell. 1993; 74(2):395-404. DOI: 10.1016/0092-8674(93)90429-t. View

10.

Raymond S, JACKSON I . The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina. Curr Biol. 1995; 5(11):1286-95. DOI: 10.1016/s0960-9822(95)00255-7. View

11.

Steingrimsson E, Nii A, Fisher D, Ferre-DAmare A, McCormick R, Russell L . The semidominant Mi(b) mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization. EMBO J. 1996; 15(22):6280-9. PMC: 452451. View

12.

Maw M, Kennedy B, Knight A, Bridges R, Roth K, Mani E . Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa. Nat Genet. 1997; 17(2):198-200. DOI: 10.1038/ng1097-198. View

13.

Evans B, Smith S . Analysis of esterification of retinoids in the retinal pigmented epithelium of the Mitf-vit (vitiligo) mutant mouse. Mol Vis. 1998; 3:11. View

14.

Nakayama A, Nguyen M, Chen C, Opdecamp K, Hodgkinson C, Arnheiter H . Mutations in microphthalmia, the mouse homolog of the human deafness gene MITF, affect neuroepithelial and neural crest-derived melanocytes differently. Mech Dev. 1998; 70(1-2):155-66. DOI: 10.1016/s0925-4773(97)00188-3. View

15.

Strauss O . The retinal pigment epithelium in visual function. Physiol Rev. 2005; 85(3):845-81. DOI: 10.1152/physrev.00021.2004. View

16.

Hou L, Pavan W . Transcriptional and signaling regulation in neural crest stem cell-derived melanocyte development: do all roads lead to Mitf?. Cell Res. 2008; 18(12):1163-76. DOI: 10.1038/cr.2008.303. View

17.

Masuda T, Esumi N . SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium. J Biol Chem. 2010; 285(35):26933-26944. PMC: 2930693. DOI: 10.1074/jbc.M110.130294. View

18.

Tang P, Fan J, Goletz P, Wheless L, Crouch R . Effective and sustained delivery of hydrophobic retinoids to photoreceptors. Invest Ophthalmol Vis Sci. 2010; 51(11):5958-64. PMC: 3061517. DOI: 10.1167/iovs.10-5766. View

19.

Ma X, Pan L, Jin X, Dai X, Li H, Wen B . Microphthalmia-associated transcription factor acts through PEDF to regulate RPE cell migration. Exp Cell Res. 2011; 318(3):251-61. DOI: 10.1016/j.yexcr.2011.11.002. View

20.

Tang P, Kono M, Koutalos Y, Ablonczy Z, Crouch R . New insights into retinoid metabolism and cycling within the retina. Prog Retin Eye Res. 2012; 32:48-63. PMC: 3746031. DOI: 10.1016/j.preteyeres.2012.09.002. View