Gene Symbol: Rpe65
Description: RPE65, retinoid isomerohydrolase
Alias: retinoid isomerohydrolase, all-trans-retinyl-palmitate hydrolase, meso-zeaxanthin isomerase, retinal pigment epithelium 65, retinal pigment epithelium 65-like, retinal pigment epithelium-specific 65 kDa protein, retinal pigment epithelium-specific protein 65, retinol isomerase
Species: rat
Products:     Rpe65

Top Publications

  1. Woodruff M, Wang Z, Chung H, Redmond T, Fain G, Lem J. Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis. Nat Genet. 2003;35:158-64 pubmed
    Mutations in Rpe65 disrupt synthesis of the opsin chromophore ligand 11-cis-retinal and cause Leber congenital amaurosis (LCA), a severe, early-onset retinal dystrophy...
  2. Daiger S, Sullivan L, Bowne S. Genes and mutations causing retinitis pigmentosa. Clin Genet. 2013;84:132-41 pubmed publisher
    ..In this review, we summarize the current approaches to gene discovery and mutation detection for RP, and indicate pitfalls and unsolved problems. Similar considerations apply to other forms of inherited retinal disease. ..
  3. Huang J, Possin D, Saari J. Localizations of visual cycle components in retinal pigment epithelium. Mol Vis. 2009;15:223-34 pubmed
    ..Three visual cycle enzymes (RDH5, LRAT, and RPE65) were restricted to the somata of RPE cells and were not detected within apical processes...
  4. Sheridan C, Boyer N, Crouch R, Koutalos Y. RPE65 and the Accumulation of Retinyl Esters in Mouse Retinal Pigment Epithelium. Photochem Photobiol. 2017;93:844-848 pubmed publisher
    The RPE65 protein of the retinal pigment epithelium (RPE) enables the conversion of retinyl esters to the visual pigment chromophore 11-cis retinal...
  5. Rajala A, Anderson R, Ma J, Lem J, Al Ubaidi M, Rajala R. G-protein-coupled receptor rhodopsin regulates the phosphorylation of retinal insulin receptor. J Biol Chem. 2007;282:9865-73 pubmed
    ..phosphorylation of the IR is signaled through bleachable rhodopsin, we examined IR activation in retinas from RPE65(-/-) mice that are deficient in opsin chromophore...
  6. Manes G, Leducq R, Kucharczak J, Pages A, Schmitt Bernard C, Hamel C. Rat messenger RNA for the retinal pigment epithelium-specific protein RPE65 gradually accumulates in two weeks from late embryonic days. FEBS Lett. 1998;423:133-7 pubmed
    The RPE65 protein appears late during the retinal development. To study the basis for this regulation, the rat RPE65 cDNA was sequenced and the mRNA subsequently quantitated at various stages by competitive RT-PCR...
  7. Hinterhuber G, Cauza K, Dingelmaier Hovorka R, Diem E, Horvat R, Wolff K, et al. Expression of RPE65, a putative receptor for plasma retinol-binding protein, in nonmelanocytic skin tumours. Br J Dermatol. 2005;153:785-9 pubmed
    In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis...
  8. Golczak M, Maeda A, Bereta G, Maeda T, Kiser P, Hunzelmann S, et al. Metabolic basis of visual cycle inhibition by retinoid and nonretinoid compounds in the vertebrate retina. J Biol Chem. 2008;283:9543-54 pubmed publisher
    ..specific inhibitor of the retinoid cycle among the tested compounds and that it targets the retinoid isomerase, RPE65. Hydrophobic primary amines like farnesylamine also showed inhibitory potency but a short duration of action, ..
  9. Wright C, Chrenek M, Feng W, Getz S, Duncan T, Pardue M, et al. The Rpe65 rd12 allele exerts a semidominant negative effect on vision in mice. Invest Ophthalmol Vis Sci. 2014;55:2500-15 pubmed publisher
    The rd12 mouse was reported as a recessively inherited Rpe65 mutation. We asked if the rd12 mutation resides in Rpe65 and how the mutation manifests itself. ..

More Information


  1. Beatrice J, Wenzel A, REme C, Grimm C. Increased light damage susceptibility at night does not correlate with RPE65 levels and rhodopsin regeneration in rats. Exp Eye Res. 2003;76:695-700 pubmed
    ..The rate of rhodopsin regeneration is at least partly controlled by RPE65, a protein expressed in the retinal pigment epithelium...
  2. Bowne S, Humphries M, Sullivan L, Kenna P, Tam L, Kiang A, et al. A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement. Eur J Hum Genet. 2011;19:1074-81 pubmed publisher
    ..8 Mb region on 1p31. Of 50 known genes in the region, 11 candidates, including RPE65 and PDE4B, were sequenced using di-deoxy capillary electrophoresis...
  3. Van Hooser J, Liang Y, Maeda T, Kuksa V, Jang G, He Y, et al. Recovery of visual functions in a mouse model of Leber congenital amaurosis. J Biol Chem. 2002;277:19173-82 pubmed
    ..For sustained vision the 11-cis-chromophore must be regenerated from all-trans-retinal. This requires RPE65, a dominant retinal pigment epithelium protein...
  4. Kiser P, Golczak M, Maeda A, Palczewski K. Key enzymes of the retinoid (visual) cycle in vertebrate retina. Biochim Biophys Acta. 2012;1821:137-51 pubmed publisher
    ..This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism. ..
  5. Wang N, Tosi J, Kasanuki J, Chou C, Kong J, Parmalee N, et al. Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa. Transplantation. 2010;89:911-9 pubmed publisher
    ..pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65/Rpe65 C57BL6 mice...
  6. Bridges C. Distribution of retinol isomerase in vertebrate eyes and its emergence during retinal development. Vision Res. 1989;29:1711-7 pubmed
    ..Therefore, the expression in the RPE of retinol isomerase, which is essential for the formation of rhodopsin in the developing photoreceptors, is coordinated with the ..
  7. Chen Y, Moiseyev G, Takahashi Y, Ma J. RPE65 gene delivery restores isomerohydrolase activity and prevents early cone loss in Rpe65-/- mice. Invest Ophthalmol Vis Sci. 2006;47:1177-84 pubmed
    Recent in vitro evidence has shown that RPE65 is the isomerohydrolase that converts all-trans retinyl ester to 11-cis retinal, the chromophore for visual pigments in vertebrates...
  8. Wright A, Chakarova C, Abd El Aziz M, Bhattacharya S. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat Rev Genet. 2010;11:273-84 pubmed publisher
    ..Although genetic and mechanistic diversity creates challenges for therapy, some approaches--particularly gene-replacement therapy--are showing considerable promise. ..
  9. Tanito M, Kaidzu S, Anderson R. Delayed loss of cone and remaining rod photoreceptor cells due to impairment of choroidal circulation after acute light exposure in rats. Invest Ophthalmol Vis Sci. 2007;48:1864-72 pubmed
    ..hours and 7 days after light exposure, and ERG amplitude, ONL and choroidal thickness and area, and rhodopsin and RPE65 expression were lower 7 or more days after light exposure than in phenyl-N-tert-butylnitrone (PBN)-injected ..
  10. Mandal M, Moiseyev G, Elliott M, Kasus Jacobi A, Li X, Chen H, et al. Alpha-phenyl-N-tert-butylnitrone (PBN) prevents light-induced degeneration of the retina by inhibiting RPE65 protein isomerohydrolase activity. J Biol Chem. 2011;286:32491-501 pubmed publisher
    ..PBN-mediated retinal protection probably occurs by slowing down the rate of rhodopsin regeneration by inhibiting RPE65 activity. PBN (50 mg/kg) protected albino Sprague-Dawley rat retinas when injected 0...
  11. Nakamura H, Yamaki K, Kondo I, Sakuragi S. Experimental autoimmune uveitis induced by immunization with retinal pigment epithelium-specific 65-kDa protein peptides. Curr Eye Res. 2005;30:673-80 pubmed
    To investigate the pathogenic potential and sites of retinal pigment epithelium-specific 65-kDa protein (RPE65) for inducing experimental autoimmune uveitis (EAU) in Lewis rats...
  12. Kirwin S, Kanaly S, Hansen C, Cairns B, Ren M, Edelman J. Retinal gene expression and visually evoked behavior in diabetic long evans rats. Invest Ophthalmol Vis Sci. 2011;52:7654-63 pubmed publisher
    ..including lecithin/retinol acyltransferase (LRAT), retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65), and RPE retinal G protein-coupled receptor (RGR)...
  13. Samardzija M, von Lintig J, Tanimoto N, Oberhauser V, Thiersch M, Reme C, et al. R91W mutation in Rpe65 leads to milder early-onset retinal dystrophy due to the generation of low levels of 11-cis-retinal. Hum Mol Genet. 2008;17:281-92 pubmed
    b>RPE65 is a retinal pigment epithelial protein essential for the regeneration of 11-cis-retinal, the chromophore of cone and rod visual pigments...
  14. Wenzel A, von Lintig J, Oberhauser V, Tanimoto N, Grimm C, Seeliger M. RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice. Invest Ophthalmol Vis Sci. 2007;48:534-42 pubmed
    ..In addition, these mice were bred to retinal pigment epithelial protein 65 (Rpe65(-/-))-deficient mice to study the role of RPE65...
  15. Bridges C, Alvarez R. The visual cycle operates via an isomerase acting on all-trans retinol in the pigment epithelium. Science. 1987;236:1678-80 pubmed
    ..chromatography have now been used to demonstrate the existence of an eye-specific, membrane-bound enzyme (retinol isomerase) that converts all-trans to 11-cis retinol in the dark...
  16. Kondo H, Qin M, Mizota A, Kondo M, Hayashi H, Hayashi K, et al. A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest Ophthalmol Vis Sci. 2004;45:4433-9 pubmed
    ..1145T-->C, F382S) and CNGB1 (c.3444 + 1G-->A). The other was a mutation in RPE65 (c.1543C-->T, R515W), which is known to cause Leber's congenital amaurosis...
  17. Shyam R, Gorusupudi A, Nelson K, Horvath M, Bernstein P. RPE65 has an additional function as the lutein to meso-zeaxanthin isomerase in the vertebrate eye. Proc Natl Acad Sci U S A. 2017;114:10882-10887 pubmed publisher
    ..In the present study, we show that RPE65, the isomerohydrolase enzyme of the vertebrate visual cycle that catalyzes the isomerization of all-trans-..