Abca4

Summary

Gene Symbol: Abca4
Description: ATP-binding cassette, sub-family A (ABC1), member 4
Alias: AW050280, Abc10, Abcr, D430003I15Rik, RmP, retinal-specific ATP-binding cassette transporter, ATP-binding cassette 10, ATP-binding cassette sub-family A member 4, RIM ABC transporter, Rim protein
Species: mouse
Products:     Abca4

Top Publications

  1. Weng J, Mata N, Azarian S, Tzekov R, Birch D, Travis G. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell. 1999;98:13-23 pubmed
    b>Rim protein (RmP) is an ABC transporter of unknown function in rod outer segment discs. The human gene for RmP (ABCR) is affected in several recessive retinal degenerations...
  2. Pawar A, Qtaishat N, Little D, Pepperberg D. Recovery of rod photoresponses in ABCR-deficient mice. Invest Ophthalmol Vis Sci. 2008;49:2743-55 pubmed publisher
    The ABCR protein of the rod outer segment is thought to facilitate movement of the all-trans retinal photoproduct of rhodopsin bleaching out of the disc lumen...
  3. 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
    ..reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities ..
  4. Kim S, Fishkin N, Kong J, Nakanishi K, Allikmets R, Sparrow J. Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E. Proc Natl Acad Sci U S A. 2004;101:11668-72 pubmed
    ..Here we show that an amino acid variant in murine Rpe65, a visual-cycle protein required for the regeneration of 11-cis-retinal, is associated with reduced A2E accumulation. ..
  5. Allikmets R, Singh N, Sun H, Shroyer N, Hutchinson A, Chidambaram A, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;15:236-46 pubmed
    ..This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in ..
  6. Mata N, Weng J, Travis G. Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci U S A. 2000;97:7154-9 pubmed
    ..Previously, we generated mice with a knockout mutation in the abcr gene. This gene encodes rim protein (RmP), an ATP-binding cassette transporter in rod outer segments...
  7. 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 clearance.
  8. 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, ..
  9. 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

More Information

Publications75

  1. Nasonkin I, Illing M, Koehler M, Schmid M, Molday R, Weber B. Mapping of the rod photoreceptor ABC transporter (ABCR) to 1p21-p22.1 and identification of novel mutations in Stargardt's disease. Hum Genet. 1998;102:21-6 pubmed
    ..the homologous human gene and demonstrate that it is identical to the photoreceptor cell-specific ABC transporter (ABCR) recently shown to be mutated in Stargardt's disease...
  2. 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
    ..b>Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated ..
  3. Beaty T, Murray J, Marazita M, Munger R, Ruczinski I, Hetmanski J, et al. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nat Genet. 2010;42:525-9 pubmed publisher
    ..704, 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5...
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. Radu R, Mata N, Bagla A, Travis G. Light exposure stimulates formation of A2E oxiranes in a mouse model of Stargardt's macular degeneration. Proc Natl Acad Sci U S A. 2004;101:5928-33 pubmed
    Recessive Stargardt's macular degeneration is a blinding disease of children caused by mutations in the ABCA4 (ABCR) gene...
  8. Guha S, Baltazar G, Tu L, Liu J, Lim J, Lu W, et al. Stimulation of the D5 dopamine receptor acidifies the lysosomal pH of retinal pigmented epithelial cells and decreases accumulation of autofluorescent photoreceptor debris. J Neurochem. 2012;122:823-33 pubmed publisher
    ..D5DR stimulation also acidified lysosomes of retinal pigmented epithelial cells from elderly ABCA4(-/-) mice, a model of recessive Stargardt's retinal degeneration...
  9. Sparrow J, Blonska A, Flynn E, Duncker T, Greenberg J, Secondi R, et al. Quantitative fundus autofluorescence in mice: correlation with HPLC quantitation of RPE lipofuscin and measurement of retina outer nuclear layer thickness. Invest Ophthalmol Vis Sci. 2013;54:2812-20 pubmed publisher
  10. Quazi F, Lenevich S, Molday R. ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nat Commun. 2012;3:925 pubmed publisher
    ..Prokaryotic ABC transporters function either as exporters or importers. Here we show that ABCA4, an ABC transporter found in retinal photoreceptor cells and associated with Stargardt macular degeneration, is a ..
  11. Anderson O, Finkelstein A, Shima D. A2E induces IL-1ß production in retinal pigment epithelial cells via the NLRP3 inflammasome. PLoS ONE. 2013;8:e67263 pubmed publisher
    ..We hypothesise that these molecules may act as danger signals, causing the production of inflammatory chemokines and cytokines by the retinal pigment epithelium, via activation of pattern recognition receptors...
  12. Secondi R, Kong J, Blonska A, Staurenghi G, Sparrow J. Fundus autofluorescence findings in a mouse model of retinal detachment. Invest Ophthalmol Vis Sci. 2012;53:5190-7 pubmed publisher
    ..hyaluronic acid (Healon) or sterile balanced salt solution (BSS) into the subretinal space of 4-5-day-old albino Abca4 null mutant and Abca4 wild-type mice...
  13. 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
    ..Biosynthetic 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, ..
  14. Zhang Y, Seo S, Bhattarai S, Bugge K, Searby C, Zhang Q, et al. BBS mutations modify phenotypic expression of CEP290-related ciliopathies. Hum Mol Genet. 2014;23:40-51 pubmed publisher
    ..Our data indicate that genetic interactions between BBSome components and CEP290 could underlie the variable expression and overlapping phenotypes of ciliopathies caused by CEP290 mutations. ..
  15. 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
    ..which indicates 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...
  16. 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
    ..This fluorophore was also detected in the eyecup extracts of Abca4(-/-)Rdh8(-/-) (Abca4 encodes ATP-binding cassette transporter 4 and Rdh8 encodes retinol dehydrogenase 8) mice, an ..
  17. Zhang N, Tsybovsky Y, Kolesnikov A, Rozanowska M, Swider M, Schwartz S, et al. Protein misfolding and the pathogenesis of ABCA4-associated retinal degenerations. Hum Mol Genet. 2015;24:3220-37 pubmed publisher
    Mutations in the ABCA4 gene are a common cause of autosomal recessive retinal degeneration...
  18. Müller P, Gliem M, Mangold E, Bolz H, Finger R, McGuinness M, et al. Monoallelic ABCA4 Mutations Appear Insufficient to Cause Retinopathy: A Quantitative Autofluorescence Study. Invest Ophthalmol Vis Sci. 2015;56:8179-86 pubmed publisher
    To investigate the effect of ABCA4 mutation status on lipofuscin-related quantitative autofluorescence (qAF) in humans and on bisretinoid accumulation in mice...
  19. 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
    ..Finally, we provide evidence for a crucial role of lecithin: retinol acyltransferase activity in mediating tissue specific absorption and long lasting therapeutic effects of retinoid-based visual cycle inhibitors. ..
  20. Reyes Reveles J, Dhingra A, Alexander D, Bragin A, Philp N, Boesze Battaglia K. Phagocytosis-dependent ketogenesis in retinal pigment epithelium. J Biol Chem. 2017;292:8038-8047 pubmed publisher
    ..An even more pronounced shift in maximal β-HB production was observed in the Abca4-/- RPE, in which loss of the ATP-binding cassette A4 transporter results in defective phagosome ..
  21. Ueda K, Zhao J, Kim H, Sparrow J. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration. Proc Natl Acad Sci U S A. 2016;113:6904-9 pubmed publisher
    ..and all-trans-retinal dimer-phosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4(-/-) mice reared in cyclic light compared with darkness...
  22. 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
    ..b>Abca4(-/-) and Rdh8(-/-)/Abca4(-/-) mice that are models of accelerated bisretinoid formation were studied and pre-..
  23. 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. ..
  24. Liu J, Lu W, Reigada D, Nguyen J, Laties A, Mitchell C. Restoration of lysosomal pH in RPE cells from cultured human and ABCA4(-/-) mice: pharmacologic approaches and functional recovery. Invest Ophthalmol Vis Sci. 2008;49:772-80 pubmed publisher
    ..Consequently, treatment to lower perturbed lysosomal pH levels may enhance degradative activity...
  25. Wang Q, Xu Y, Zhou W, Zhong L, Wen Z, Yu H, et al. The viral oncoprotein HBx of Hepatitis B virus promotes the growth of hepatocellular carcinoma through cooperating with the cellular oncoprotein RMP. Int J Biol Sci. 2014;10:1181-92 pubmed publisher
    ..Our previous work demonstrated that RMP is a cellular oncogene (C-oncogene) required for the proliferation of hepatocellular carcinoma (HCC) cells...
  26. 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. ..
  27. 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...
  28. 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
    ..for toll-like receptor 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...
  29. Charbel Issa P, Barnard A, Singh M, Carter E, Jiang Z, Radu R, et al. Fundus autofluorescence in the Abca4(-/-) mouse model of Stargardt disease--correlation with accumulation of A2E, retinal function, and histology. Invest Ophthalmol Vis Sci. 2013;54:5602-12 pubmed publisher
    To investigate fundus autofluorescence (AF) characteristics in the Abca4(-/-) mouse, an animal model for AMD and Stargardt disease, and to correlate findings with functional, structural, and biochemical assessments.
  30. Liu J, Lu W, Guha S, Baltazar G, Coffey E, Laties A, et al. Cystic fibrosis transmembrane conductance regulator contributes to reacidification of alkalinized lysosomes in RPE cells. Am J Physiol Cell Physiol. 2012;303:C160-9 pubmed publisher
    ..Activation of CFTR acidified RPE lysosomes from the ABCA4(-/-) mouse model of recessive Stargardt's disease, whose lysosomes are considerably alkalinized...
  31. 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
    ..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)...
  32. Han Z, Conley S, Makkia R, Cooper M, Naash M. DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice. J Clin Invest. 2012;122:3221-6 pubmed publisher
    Mutations in the photoreceptor-specific flippase ABCA4 are associated with Stargardt disease and many other forms of retinal degeneration that currently lack curative therapies...
  33. 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...
  34. Lenis T, Sarfare S, Jiang Z, Lloyd M, Bok D, Radu R. Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease. Proc Natl Acad Sci U S A. 2017;114:3987-3992 pubmed publisher
    Recessive Stargardt macular degeneration (STGD1) is caused by mutations in the gene for the ABCA4 transporter in photoreceptor outer segments...
  35. Fishkin N, Sparrow J, Allikmets R, Nakanishi K. Isolation and characterization of a retinal pigment epithelial cell fluorophore: an all-trans-retinal dimer conjugate. Proc Natl Acad Sci U S A. 2005;102:7091-6 pubmed
    ..HPLC analysis of eye-cups that included RPE and isolated neural retina from Abcr-/- mice and RPE isolated from human donor eyes revealed the presence of a pigment with the same UV-visible ..
  36. Wu L, Nagasaki T, Sparrow J. Photoreceptor cell degeneration in Abcr (-/-) mice. Adv Exp Med Biol. 2010;664:533-9 pubmed publisher
    Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease...
  37. Trapani I, Toriello E, de Simone S, Colella P, Iodice C, Polishchuk E, et al. Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease. Hum Mol Genet. 2015;24:6811-25 pubmed publisher
    Stargardt disease (STGD1) due to mutations in the large ABCA4 gene is the most common inherited macular degeneration in humans...
  38. Charbel Issa P, Singh M, Lipinski D, Chong N, Delori F, Barnard A, et al. Optimization of in vivo confocal autofluorescence imaging of the ocular fundus in mice and its application to models of human retinal degeneration. Invest Ophthalmol Vis Sci. 2012;53:1066-75 pubmed publisher
    ..790 nm) fundus AF imaging was performed in various mouse strains and disease models (129S2, C57Bl/6, Abca4(-/-), C3H-Pde6b(rd1/rd1), Rho(-/-), and BALB/c mice) using a commercially available scanning laser ophthalmoscope...
  39. Guha S, Baltazar G, Coffey E, Tu L, Lim J, Beckel J, et al. Lysosomal alkalinization, lipid oxidation, and reduced phagosome clearance triggered by activation of the P2X7 receptor. FASEB J. 2013;27:4500-9 pubmed publisher
    ..of mouse RPE; mRNA expression of P2X7R and extracellular ATP marker NTPDase1 was raised in RPE tissue from the ABCA4(-/-) mouse model of Stargardt's retinal degeneration...
  40. Yamamoto K, Yoon K, Ueda K, Hashimoto M, Sparrow J. A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine. Invest Ophthalmol Vis Sci. 2011;52:9084-90 pubmed publisher
    ..The formation of bisretinoid is accentuated in some forms of retinal degeneration. The detection of a novel bisretinoid fluorophore that is a conjugate of all-trans-retinal and glycerophosphoethanolamine is reported...
  41. Qtaishat N, Pepperberg D. Preservation of retinoid influx into eye tissues of ABCR-deficient mice. Curr Eye Res. 2007;32:1073-82 pubmed
    ..radiolabeling technique, we investigated the movement of retinoid into the retinal pigment epithelium (RPE) of the abcr-/- mouse, which lacks the photoreceptor ABCR protein and is a model for Stargardt disease...
  42. 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).
  43. Mata N, Tzekov R, Liu X, Weng J, Birch D, Travis G. Delayed dark-adaptation and lipofuscin accumulation in abcr+/- mice: implications for involvement of ABCR in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2001;42:1685-90 pubmed
    To examine the ocular phenotype in mice heterozygous for a null mutation in the abcr gene.
  44. Maeda A, Maeda T, Imanishi Y, Sun W, Jastrzebska B, Hatala D, et al. Retinol dehydrogenase (RDH12) protects photoreceptors from light-induced degeneration in mice. J Biol Chem. 2006;281:37697-704 pubmed
    ..Thus, severe visual impairments of individuals with null mutations in RDH12 may likely be caused by light damage(1). ..
  45. Azarian S, Travis G. The photoreceptor rim protein is an ABC transporter encoded by the gene for recessive Stargardt's disease (ABCR). FEBS Lett. 1997;409:247-52 pubmed
    b>Rim protein (RmP) is a high-Mr membrane glycoprotein that has been localized to the rims of photoreceptor outer segment discs, but its molecular identity is unknown...
  46. Wu L, Ueda K, Nagasaki T, Sparrow J. Light damage in Abca4 and Rpe65rd12 mice. Invest Ophthalmol Vis Sci. 2014;55:1910-8 pubmed publisher
    ..the propensity for light damage in mutant mice having elevated lipofuscin due to deficiency in the ATP-binding cassette (ABC) transporter Abca4 (Abca4(-/-) mice) and in mice devoid of lipofuscin owing to absence of Rpe65 (Rpe65(rd12)).
  47. Radu R, Yuan Q, Hu J, Peng J, Lloyd M, Nusinowitz S, et al. Accelerated accumulation of lipofuscin pigments in the RPE of a mouse model for ABCA4-mediated retinal dystrophies following Vitamin A supplementation. Invest Ophthalmol Vis Sci. 2008;49:3821-9 pubmed publisher
    ..Loss-of-function mutations in the ABCA4 gene are responsible for a subset of recessive retinitis pigmentosa...
  48. 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 with rod-only and cone-like-only retinas in addition to progenies of such mice inbred with Rdh8(-/-) Abca4(-/-) mice...
  49. Grey A, Crouch R, Koutalos Y, Schey K, Ablonczy Z. Spatial localization of A2E in the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2011;52:3926-33 pubmed publisher
    ..The best-characterized components of lipofuscin are A2E and its oxides, but a direct spatial correlation with lipofuscin has not previously been possible...
  50. Li Q, Uitto J. Expression of the Abca-subfamily of genes in Abcc6-/- mice--upregulation of Abca4. Exp Dermatol. 2011;20:452-4 pubmed publisher
    ..The results indicated variable levels of mRNA for different Abca genes in the liver; however, only one of them, Abca4, was significantly, ?6.5-fold, upregulated in the Abcc6(-/-) mice in comparison with wild-type mice...
  51. Ma L, Kaufman Y, Zhang J, Washington I. C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease. J Biol Chem. 2011;286:7966-74 pubmed publisher
    ..macular degeneration, occurs in approximately one in 10,000 people and results from genetic defects in the ABCA4 gene...
  52. 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. ..
  53. Radu R, Hu J, Yuan Q, Welch D, Makshanoff J, Lloyd M, et al. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration. J Biol Chem. 2011;286:18593-601 pubmed publisher
    ..feature of recessive Stargardt macular dystrophy, a blinding disease caused by dysfunction or loss of the ABCA4 transporter in rods and cones...
  54. Maiti P, Kong J, Kim S, Sparrow J, Allikmets R, Rando R. Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation. Biochemistry. 2006;45:852-60 pubmed
    ..These antagonists will also be used to probe the molecular function of RPE65 in vision. ..
  55. Charbel Issa P, Barnard A, Herrmann P, Washington I, MacLaren R. Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization. Proc Natl Acad Sci U S A. 2015;112:8415-20 pubmed publisher
    Stargardt disease, an ATP-binding cassette, subfamily A, member 4 (ABCA4)-related retinopathy, is a genetic condition characterized by the accelerated accumulation of lipofuscin in the retinal pigment epithelium, degeneration of the ..
  56. 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
    ..b>Abca4(-/-)Rdh8(-/-) mice featuring defective atRAL clearance were used to examine the one or more underlying molecular ..
  57. Conley S, Cai X, Makkia R, Wu Y, Sparrow J, Naash M. Increased cone sensitivity to ABCA4 deficiency provides insight into macular vision loss in Stargardt's dystrophy. Biochim Biophys Acta. 2012;1822:1169-79 pubmed publisher
    Autosomal recessive Stargardt macular dystrophy is caused by mutations in the photoreceptor disc rim protein ABCA4/ABCR...
  58. Bui T, Han Y, Radu R, Travis G, Mata N. Characterization of native retinal fluorophores involved in biosynthesis of A2E and lipofuscin-associated retinopathies. J Biol Chem. 2006;281:18112-9 pubmed
    Mutations in the photoreceptor-specific ABCA4 gene are associated with several inherited retinal and macular degenerations...
  59. 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...
  60. Dobri N, Qin Q, Kong J, Yamamoto K, Liu Z, Moiseyev G, et al. A1120, a nonretinoid RBP4 antagonist, inhibits formation of cytotoxic bisretinoids in the animal model of enhanced retinal lipofuscinogenesis. Invest Ophthalmol Vis Sci. 2013;54:85-95 pubmed publisher
    ..We evaluated in vitro and in vivo properties of the new nonretinoid RBP4 antagonist, A1120...
  61. Quazi F, Molday R. ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal. Proc Natl Acad Sci U S A. 2014;111:5024-9 pubmed publisher
    ..Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-..
  62. Tan L, Toops K, Lakkaraju A. Protective responses to sublytic complement in the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2016;113:8789-94 pubmed publisher
    ..Using polarized primary RPE and the pigmented Abca4(-/-) Stargardt disease mouse model, we provide evidence for two protective responses occurring within minutes of ..
  63. Tsybovsky Y, Wang B, Quazi F, Molday R, Palczewski K. Posttranslational modifications of the photoreceptor-specific ABC transporter ABCA4. Biochemistry. 2011;50:6855-66 pubmed publisher
    b>ABCA4 is a photoreceptor-specific ATP-binding cassette transporter implicated in the clearance of all-trans-retinal produced in the retina during light perception...
  64. 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
    ..b>Abca4(-/-)Rdh8(-/-) mice, which mimic many features of human retinal degeneration, allowed us to determine the sequence ..
  65. 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 ..
  66. 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
    ..biochemical methods using ARPE-19 cells, 661 W cells, cultured neural retinas and a retinal degeneration model, Abca4(-/-)Rdh8(-/-) mice...