Rdh8

Summary

Gene Symbol: Rdh8
Description: retinol dehydrogenase 8
Alias: Gm182, prRDH, retinol dehydrogenase 8
Species: mouse
Products:     Rdh8

Top Publications

  1. Maeda A, Maeda T, Golczak M, Palczewski K. Retinopathy in mice induced by disrupted all-trans-retinal clearance. J Biol Chem. 2008;283:26684-93 pubmed publisher
    ..Here we report that mice lacking both the ATP-binding cassette transporter 4 (Abca4) and enzyme retinol dehydrogenase 8 (Rdh8), proteins critical for all-trans-retinal clearance from photoreceptors, developed severe RPE/..
  2. Maeda A, Maeda T, Golczak M, Chou S, Desai A, Hoppel C, et al. Involvement of all-trans-retinal in acute light-induced retinopathy of mice. J Biol Chem. 2009;284:15173-83 pubmed publisher
    ..all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-..
  3. Palczewska G, Maeda T, Imanishi Y, Sun W, Chen Y, Williams D, et al. Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal condensation products in mouse eyes. Nat Med. 2010;16:1444-9 pubmed publisher
  4. Maeda A, Maeda T, Imanishi Y, Kuksa V, Alekseev A, Bronson J, et al. Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo. J Biol Chem. 2005;280:18822-32 pubmed
    ..Photoreceptor-specific retinol dehydrogenase (prRDH) catalyzes reduction of all-trans-retinal to all-trans-retinol and is thought to be a key enzyme in the retinoid ..
  5. Maeda A, Golczak M, Maeda T, Palczewski K. Limited roles of Rdh8, Rdh12, and Abca4 in all-trans-retinal clearance in mouse retina. Invest Ophthalmol Vis Sci. 2009;50:5435-43 pubmed publisher
    ..The protective roles were examined of the all-trans-RDHs, Rdh8 and Rdh12, and the ATP-binding cassette transporter Abca4, retinoid cycle enzymes involved in all-trans-retinal ..
  6. Zhao J, Liao Y, Chen J, Dong X, Gao Z, Zhang H, et al. Aberrant Buildup of All-Trans-Retinal Dimer, a Nonpyridinium Bisretinoid Lipofuscin Fluorophore, Contributes to the Degeneration of the Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci. 2017;58:1063-1075 pubmed publisher
    ..all-trans-retinal dimer (atRAL dimer) was found to be much more abundant than that of A2E in eyes of Abca4-/-Rdh8-/- double-knockout (DKO) mice, a rodent model showing the typical characteristics of retinopathies in AMD patients...
  7. Maeda A, Maeda T, Sun W, Zhang H, Baehr W, Palczewski K. Redundant and unique roles of retinol dehydrogenases in the mouse retina. Proc Natl Acad Sci U S A. 2007;104:19565-70 pubmed
    ..Rdh12 knockout mice were found to be susceptible to light-induced photoreceptor apoptosis, whereas Rdh5 and Rdh8 knockout mice displayed only delayed dark adaptation...
  8. Parmar T, Parmar V, Arai E, Sahu B, Perusek L, Maeda A. Acute Stress Responses Are Early Molecular Events of Retinal Degeneration in Abca4-/-Rdh8-/- Mice After Light Exposure. Invest Ophthalmol Vis Sci. 2016;57:3257-67 pubmed publisher
    Mice lacking ATP-binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8) mimic features of human Stargardt disease and age-related macular degeneration...
  9. Palczewska G, Dong Z, Golczak M, Hunter J, Williams D, Alexander N, et al. Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye. Nat Med. 2014;20:785-9 pubmed publisher
    ..This imaging approach has the potential to detect early molecular changes in retinoid metabolism that trigger light- and AMD-induced retinal defects and to assess the effectiveness of treatments for these conditions. ..

More Information

Publications33

  1. Sawada O, Perusek L, Kohno H, Howell S, Maeda A, Matsuyama S, et al. All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis. Exp Eye Res. 2014;123:27-36 pubmed publisher
    ..methods using ARPE-19 cells, 661 W cells, cultured neural retinas and a retinal degeneration model, Abca4(-/-)Rdh8(-/-) mice...
  2. Maeda T, Maeda A, Matosky M, Okano K, Roos S, Tang J, et al. Evaluation of potential therapies for a mouse model of human age-related macular degeneration caused by delayed all-trans-retinal clearance. Invest Ophthalmol Vis Sci. 2009;50:4917-25 pubmed publisher
    Evaluate the efficacy of potential therapeutics in Rdh8(-/-)Abca4(-/-) mice, a rodent model of human age-related macular degeneration (AMD).
  3. Chen C, Thompson D, Koutalos Y. Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12. J Biol Chem. 2012;287:24662-70 pubmed publisher
    ..Previous studies have shown that RDH8 localizes to photoreceptor outer segments and is a strong candidate for performing this role...
  4. Chen Y, Palczewska G, Mustafi D, Golczak M, Dong Z, Sawada O, et al. Systems pharmacology identifies drug targets for Stargardt disease-associated retinal degeneration. J Clin Invest. 2013;123:5119-34 pubmed publisher
    ..These findings demonstrate a strategy for the identification of new drug candidates and FDA-approved drugs for the treatment of monogenic and complex diseases. ..
  5. Kohno H, Maeda T, Perusek L, Pearlman E, Maeda A. CCL3 production by microglial cells modulates disease severity in murine models of retinal degeneration. J Immunol. 2014;192:3816-27 pubmed publisher
    ..In this study, we examined the role of chemokines in the Abca4(-/-)Rdh8(-/-) mouse model of Stargardt disease and the Mertk(-/-) mouse model of retinitis pigmentosa...
  6. Zhou J, Ueda K, Zhao J, Sparrow J. Correlations between Photodegradation of Bisretinoid Constituents of Retina and Dicarbonyl Adduct Deposition. J Biol Chem. 2015;290:27215-27 pubmed publisher
    ..Abca4(-/-) and Rdh8(-/-)/Abca4(-/-) mice that are models of accelerated bisretinoid formation were studied and pre-exposure of mice to ..
  7. Okano K, Maeda A, Chen Y, Chauhan V, Tang J, Palczewska G, et al. Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage. J Neurochem. 2012;121:146-56 pubmed publisher
    ..mice lacking enzymes that clear all-trans-retinal from the retina, ATP-binding cassette transporter 4 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy...
  8. Shiose S, Chen Y, Okano K, Roy S, Kohno H, Tang J, et al. Toll-like receptor 3 is required for development of retinopathy caused by impaired all-trans-retinal clearance in mice. J Biol Chem. 2011;286:15543-55 pubmed publisher
    ..3 (TLR3) in cone-rod dystrophy (CORD) of mice lacking ATP-binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8), proteins critical for all-trans-retinal clearance in the retina...
  9. Chen Y, Okano K, Maeda T, Chauhan V, Golczak M, Maeda A, et al. Mechanism of all-trans-retinal toxicity with implications for stargardt disease and age-related macular degeneration. J Biol Chem. 2012;287:5059-69 pubmed publisher
    ..Abca4(-/-)Rdh8(-/-) mice featuring defective atRAL clearance were used to examine the one or more underlying molecular mechanisms, ..
  10. Zhang J, Kiser P, Badiee M, Palczewska G, Dong Z, Golczak M, et al. Molecular pharmacodynamics of emixustat in protection against retinal degeneration. J Clin Invest. 2015;125:2781-94 pubmed publisher
    ..Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. ..
  11. Fontaine V, Monteiro E, Brazhnikova E, Lesage L, Balducci C, Guibout L, et al. Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo. PLoS ONE. 2016;11:e0167793 pubmed publisher
    ..In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected ..
  12. Maeda A, Palczewska G, Golczak M, Kohno H, Dong Z, Maeda T, et al. Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice. Proc Natl Acad Sci U S A. 2014;111:E1428-37 pubmed publisher
    ..Abca4(-/-)Rdh8(-/-) mice, which mimic many features of human retinal degeneration, allowed us to determine the sequence of light-..
  13. Wu Y, Jin Q, Yao K, Zhao J, Chen J, Wu X, et al. Retinal metabolism in humans induces the formation of an unprecedented lipofuscin fluorophore 'pdA2E'. Biochem J. 2014;460:343-52 pubmed publisher
    ..eyecup extracts of Abca4(-/-)Rdh8(-/-) (Abca4 encodes ATP-binding cassette transporter 4 and Rdh8 encodes retinol dehydrogenase 8) mice, an AMD/recessive Stargardt's disease model...
  14. Chen Y, Sawada O, Kohno H, Le Y, SUBAUSTE C, Maeda T, et al. Autophagy protects the retina from light-induced degeneration. J Biol Chem. 2013;288:7506-18 pubmed publisher
    ..the activation of oxidative stress, was recorded in response to light illumination in retinas of Abca4(-/-)Rdh8(-/-) mice, which showed delayed clearance of all-trans-retinal after light exposure...
  15. Schur R, Sheng L, Sahu B, Yu G, Gao S, Yu X, et al. Manganese-Enhanced MRI for Preclinical Evaluation of Retinal Degeneration Treatments. Invest Ophthalmol Vis Sci. 2015;56:4936-42 pubmed publisher
    ..Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated with ..
  16. Parker R, Crouch R. Retinol dehydrogenases (RDHs) in the visual cycle. Exp Eye Res. 2010;91:788-92 pubmed publisher
    ..Within rods, RDH8 is largely responsible for the reduction of all-trans retinal with possible assistance from RDH12...
  17. Flynn E, Ueda K, Auran E, Sullivan J, Sparrow J. Fundus autofluorescence and photoreceptor cell rosettes in mouse models. Invest Ophthalmol Vis Sci. 2014;55:5643-52 pubmed publisher
    ..lens; 488-nm excitation) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired in pigmented Rdh8(-/-)/Abca4(-/-) mice (ages 1-9 months) with a confocal scanning laser ophthalmoscope (cSLO)...
  18. Wong B, Chan J, Cazenave Gassiot A, Poh R, Foo J, Galam D, et al. Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development. J Biol Chem. 2016;291:10501-14 pubmed publisher
    ..These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. ..
  19. Palczewska G, Maeda A, Golczak M, Arai E, Dong Z, Perusek L, et al. Receptor MER Tyrosine Kinase Proto-oncogene (MERTK) Is Not Required for Transfer of Bis-retinoids to the Retinal Pigmented Epithelium. J Biol Chem. 2016;291:26937-26949 pubmed publisher
    ..These observations demonstrate a novel transport mechanism between photoreceptor cells and RPE that does not involve canonical Mertk-dependent phagocytosis. ..
  20. 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;45:4210-9 pubmed
    ..Rdh5-deficient mice accumulate cis-retinyl esters, regardless of the simultaneous disruption of RPE65, opsin, and prRDH. 13-cis-Retinoids are produced at higher levels when the flow of retinoid through the cycle was increased, and ..
  21. Zhao J, Yao K, Jin Q, Jiang K, Chen J, Liu Z, et al. Preparative and biosynthetic insights into pdA2E and isopdA2E, retinal-derived fluorophores of retinal pigment epithelial lipofuscin. Invest Ophthalmol Vis Sci. 2014;55:8241-50 pubmed publisher
    ..reaction mixtures, RPE/choroids and neural retinas dissected from bovines, eyes harvested from Abca4(-/-)Rdh8(-/-) mice, irradiated samples, and enzyme-treated solutions were analyzed by HPLC, mass spectrometry, nuclear ..
  22. Maeda A, Okano K, Park P, Lem J, Crouch R, Maeda T, et al. Palmitoylation stabilizes unliganded rod opsin. Proc Natl Acad Sci U S A. 2010;107:8428-33 pubmed publisher
    ..Together, these observations provide evidence for a structural role of rhodopsin S-palmitoylation that may apply to other GPCRs as well. ..
  23. NOCIARI M, Lehmann G, Perez Bay A, Radu R, Jiang Z, Goicochea S, et al. Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium. Proc Natl Acad Sci U S A. 2014;111:E1402-8 pubmed publisher
    ..CD treatment reduced by 73% and 48% the LB content of RPE cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively...
  24. Chen Y, Palczewska G, Masuho I, Gao S, Jin H, Dong Z, et al. Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration. Sci Signal. 2016;9:ra74 pubmed publisher
    ..Our study thus supports a systems pharmacology approach to identify treatments for retinopathies, an approach that could extend to other complex disorders. ..