RPE65 and the Accumulation of Retinyl Esters in Mouse Retinal Pigment Epithelium

Overview

Journal Photochem Photobiol

Specialties Biochemistry
Biology
Chemistry

Date 2017 May 14

PMID 28500718

Citations 6

Authors

Colleen Sheridan

Nicholas P Boyer

Rosalie K Crouch

Yiannis Koutalos

Affiliations

Soon will be listed here.

Abstract

The RPE65 protein of the retinal pigment epithelium (RPE) enables the conversion of retinyl esters to the visual pigment chromophore 11-cis retinal. Fresh 11-cis retinal is generated from retinyl esters following photoisomerization of the visual pigment chromophore to all-trans during light detection. Large amounts of esters accumulate in Rpe65 mice, indicating their continuous formation when 11-cis retinal generation is blocked. We hypothesized that absence of light, by limiting the conversion of esters to 11-cis retinal, would also result in the build-up of retinyl esters in the RPE of wild-type mice. We used HPLC to quantify ester levels in organic extracts of the RPE from wild-type and Rpe65 mice. Retinyl ester levels in Sv/129 wild-type mice that were dark adapted for various intervals over a 4-week period were similar to those in mice raised in cyclic light. In C57BL/6 mice however, which contain less Rpe65 protein, dark adaptation was accompanied by an increase in ester levels compared to cyclic light controls. Retinyl ester levels were much higher in Rpe65 mice compared to wild type and kept increasing with age. The results suggest that the RPE65 role in retinyl ester homeostasis extends beyond enabling the formation of 11-cis retinal.

Citing Articles

Cell-based Therapies for Corneal and Retinal Disorders.

Ajgaonkar B, Kumaran A, Kumar S, Jain R, Dandekar P Stem Cell Rev Rep. 2023; 19(8):2650-2682.

PMID: 37704835 DOI: 10.1007/s12015-023-10623-0.

The Predicted Splicing Variant c.11+5G>A in Leads to a Reduction in mRNA Expression in a Cell-Specific Manner.

Vazquez-Dominguez I, Duijkers L, Fadaie Z, Alaerds E, Post M, van Oosten E Cells. 2022; 11(22).

PMID: 36429068 PMC: 9688607. DOI: 10.3390/cells11223640.

Retinal pigment epithelium 65 kDa protein (RPE65): An update.

Kiser P Prog Retin Eye Res. 2021; 88:101013.

PMID: 34607013 PMC: 8975950. DOI: 10.1016/j.preteyeres.2021.101013.

The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates.

Widjaja-Adhi M, Golczak M Biochim Biophys Acta Mol Cell Biol Lipids. 2019; 1865(11):158571.

PMID: 31770587 PMC: 7244374. DOI: 10.1016/j.bbalip.2019.158571.

Hamartoma-like lesions in the mouse retina: an animal model of hamartoma tumour syndrome.

Tachibana N, Touahri Y, Dixit R, David L, Adnani L, Cantrup R Dis Model Mech. 2018; 11(5).

PMID: 29716894 PMC: 5992614. DOI: 10.1242/dmm.031005.

References

Okajima T, Wiggert B, Chader G, Pepperberg D . Retinoid processing in retinal pigment epithelium of toad (Bufo marinus). J Biol Chem. 1994; 269(35):21983-9. View

Maeda A, Maeda T, Imanishi Y, Golczak M, Moise A, Palczewski K . Aberrant metabolites in mouse models of congenital blinding diseases: formation and storage of retinyl esters. Biochemistry. 2006; 45(13):4210-9. PMC: 1560103. DOI: 10.1021/bi052382x. View

Morimura H, Fishman G, Grover S, Fulton A, Berson E, Dryja T . Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Proc Natl Acad Sci U S A. 1998; 95(6):3088-93. PMC: 19699. DOI: 10.1073/pnas.95.6.3088. View

Young R, Bok D . Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol. 1969; 42(2):392-403. PMC: 2107669. DOI: 10.1083/jcb.42.2.392. View

Palczewski K, Jager S, Buczylko J, Crouch R, Bredberg D, Hofmann K . Rod outer segment retinol dehydrogenase: substrate specificity and role in phototransduction. Biochemistry. 1994; 33(46):13741-50. DOI: 10.1021/bi00250a027. View

Moiseyev G, Chen Y, Takahashi Y, Wu B, Ma J . RPE65 is the isomerohydrolase in the retinoid visual cycle. Proc Natl Acad Sci U S A. 2005; 102(35):12413-8. PMC: 1194921. DOI: 10.1073/pnas.0503460102. View

HARGRAVE P . Rhodopsin structure, function, and topography the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2001; 42(1):3-9. View

Travis G, Golczak M, Moise A, Palczewski K . Diseases caused by defects in the visual cycle: retinoids as potential therapeutic agents. Annu Rev Pharmacol Toxicol. 2006; 47:469-512. PMC: 2442882. DOI: 10.1146/annurev.pharmtox.47.120505.105225. View

Radu R, Hu J, Peng J, Bok D, Mata N, Travis G . Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells. J Biol Chem. 2008; 283(28):19730-8. PMC: 2443657. DOI: 10.1074/jbc.M801288200. View

10.

FUTTERMAN S, Hendrickson A, Bishop P, Rollins M, Vacano E . Metabolism of glucose and reduction of retinaldehyde in retinal photoreceptors. J Neurochem. 1970; 17(2):149-56. DOI: 10.1111/j.1471-4159.1970.tb02195.x. View

11.

Batten M, Imanishi Y, Maeda T, Tu D, Moise A, Bronson D . Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver. J Biol Chem. 2003; 279(11):10422-32. PMC: 1351249. DOI: 10.1074/jbc.M312410200. View

12.

Fain G, Matthews H, Cornwall M, Koutalos Y . Adaptation in vertebrate photoreceptors. Physiol Rev. 2001; 81(1):117-151. DOI: 10.1152/physrev.2001.81.1.117. View

13.

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

14.

Marlhens F, Bareil C, Griffoin J, Zrenner E, AMALRIC P, Eliaou C . Mutations in RPE65 cause Leber's congenital amaurosis. Nat Genet. 1997; 17(2):139-41. DOI: 10.1038/ng1097-139. View

15.

Imanishi Y, Batten M, Piston D, Baehr W, Palczewski K . Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye. J Cell Biol. 2004; 164(3):373-83. PMC: 1360214. DOI: 10.1083/jcb.200311079. View

16.

Ruiz A, Winston A, Lim Y, Gilbert B, Rando R, Bok D . Molecular and biochemical characterization of lecithin retinol acyltransferase. J Biol Chem. 1999; 274(6):3834-41. DOI: 10.1074/jbc.274.6.3834. View

17.

Chen C, Blakeley L, Koutalos Y . Formation of all-trans retinol after visual pigment bleaching in mouse photoreceptors. Invest Ophthalmol Vis Sci. 2009; 50(8):3589-95. PMC: 2724838. DOI: 10.1167/iovs.08-3336. View

18.

WALD G . Molecular basis of visual excitation. Science. 1968; 162(3850):230-9. DOI: 10.1126/science.162.3850.230. View

19.

Mata N, Tsin A, Chambers J . Hydrolysis of 11-cis- and all-trans-retinyl palmitate by retinal pigment epithelium microsomes. J Biol Chem. 1992; 267(14):9794-9. View

20.

STECHER H, Gelb M, SAARI J, Palczewski K . Preferential release of 11-cis-retinol from retinal pigment epithelial cells in the presence of cellular retinaldehyde-binding protein. J Biol Chem. 1999; 274(13):8577-85. DOI: 10.1074/jbc.274.13.8577. View