{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:32:19Z","timestamp":1790721139277,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":[", EY026544-01"],"award-info":[{"award-number":[", EY026544-01"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.<\/jats:p>","DOI":"10.3390\/cells9040910","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T03:40:19Z","timestamp":1586403619000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A G-Protein Coupled Receptor and Macular Degeneration"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-6942","authenticated-orcid":false,"given":"Anna G.","family":"Figueroa","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fronk, A.H., and Vargis, E. (2016). Methods for culturing retinal pigment epithelial cells: A review of current protocols and future recommendations. J. Tissue Eng., 7.","DOI":"10.1177\/2041731416650838"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/excr.1994.1176","article-title":"Separation of phenotypically distinct subpopulations of cultured human retinal pigment epithelial cells","volume":"213","author":"McKay","year":"1994","journal-title":"Exp. Cell Res."},{"key":"ref_4","first-page":"1063","article-title":"Melanin concentration in normal human retinal pigment epithelium","volume":"27","author":"Schmidt","year":"1986","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","first-page":"145","article-title":"Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes","volume":"27","author":"Weiter","year":"1986","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0014-2999(02)01416-4","article-title":"The L-3,4-dihydroxyphenylalanine transporter in human and rat epithelial intestinal cells is a type 2 hetero amino acid exchanger","volume":"441","author":"Fraga","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_7","first-page":"88","article-title":"Monitoring Of Blood L-DOPA And L-DOPA Metabolite Concentrations And Adverse Events In Patients With Advanced Parkinsons Disease Receiving L-DOPA And Amantadine Combination Therapy: A Clinical Study","volume":"4","author":"Satoh","year":"2015","journal-title":"Res. Rev. J. Pharm. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.expneurol.2004.06.009","article-title":"PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson\u2019s disease","volume":"189","author":"Doudet","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/clinchem\/39.4.629","article-title":"Measuring L-dopa in plasma and urine to monitor therapy of elderly patients with Parkinson disease treated with L-dopa and a dopa decarboxylase inhibitor","volume":"39","author":"Dutton","year":"1993","journal-title":"Clin. Chem."},{"key":"ref_10","first-page":"59","article-title":"L-dopa therapy in Parkinson\u2019s disease: A critical review of nine years\u2019 experience","volume":"101","author":"Barbeau","year":"1969","journal-title":"Can. Med. Assoc. J."},{"key":"ref_11","first-page":"1795","article-title":"Current And Experimental Therapeutics Of Parkinson\u2019s Disease","volume":"124","author":"Gracies","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1242\/jcs.1993.Supplement_17.27","article-title":"The retinal pigment epithelium: A versatile partner in vision","volume":"17","author":"Bok","year":"1993","journal-title":"J. Cell Sci. Suppl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/eye.2001.141","article-title":"The role of the retinal pigment epithelium: Topographical variation and ageing changes","volume":"15","author":"Boulton","year":"2001","journal-title":"Eye"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1600-0749.2006.00318.x","article-title":"The other pigment cell: Specification and development of the pigmented epithelium of the vertebrate eye","volume":"19","author":"Bharti","year":"2006","journal-title":"Pigment Cell Res."},{"key":"ref_15","first-page":"4333","article-title":"Expression pattern of the ocular albinism type 1 (Oa1) gene in the murine retinal pigment epithelium","volume":"41","author":"Surace","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Roffler-Tarlov, S., Liu, J.H., Naumova, E.N., Bernal-Ayala, M.M., and Mason, C.A. (2013). L-Dopa and the albino riddle: Content of L-Dopa in the developing retina of pigmented and albino mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057184"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3109\/13816819009020979","article-title":"Visual anomalies associated with albinism","volume":"11","author":"Creel","year":"1990","journal-title":"Ophthalmic Paediatr. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.visres.2010.02.003","article-title":"Arrested development: High-resolution imaging of foveal morphology in albinism","volume":"50","author":"McAllister","year":"2010","journal-title":"Vis. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/j.ophtha.2011.01.037","article-title":"The functional significance of foveal abnormalities in albinism measured using spectral-domain optical coherence tomography","volume":"118","author":"Mohammad","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/jnr.24246","article-title":"Pigmentation and vision: Is GPR143 in control?","volume":"97","author":"McKay","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1371\/journal.pbio.0060236","article-title":"L-DOPA is an endogenous ligand for OA1","volume":"6","author":"Lopez","year":"2008","journal-title":"PLoS Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1113\/jphysiol.2014.284919","article-title":"Rod electrical coupling is controlled by a circadian clock and dopamine in mouse retina","volume":"593","author":"Jin","year":"2015","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1076\/0271-3683(200003)2031-9FT195","article-title":"Expression of the extraneuronal monoamine transporter in RPE and neural retina","volume":"20","author":"Rajan","year":"2000","journal-title":"Curr. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1460-9568.2011.07734.x","article-title":"Dopamine D4 receptor activation controls circadian timing of the adenylyl cyclase 1\/cyclic AMP signaling system in mouse retina","volume":"34","author":"Jackson","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Falk, T., Congrove, N.R., Zhang, S., McCourt, A.D., Sherman, S.J., and McKay, B.S. (2012). PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers. J. Biomed. Biotechnol., 2012.","DOI":"10.1155\/2012\/278932"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2014.10.010","article-title":"Controlled exosome release from the retinal pigment epithelium insitu","volume":"129","author":"Locke","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.3390\/ijms11082875","article-title":"The Yin and Yang of VEGF and PEDF: Multifaceted neurotrophic factors and their potential in the treatment of Parkinson\u2019s disease","volume":"11","author":"Falk","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrn1176","article-title":"PEDF: A multifaceted neurotrophic factor","volume":"4","author":"Barnstable","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28917","DOI":"10.1074\/jbc.M504803200","article-title":"Extracellular trafficking of myocilin in human trabecular meshwork cells","volume":"280","author":"Hardy","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1523\/JNEUROSCI.15-07-04992.1995","article-title":"Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity","volume":"15","author":"Shivaram","year":"1995","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1073\/pnas.90.4.1526","article-title":"Pigment epithelium-derived factor: Neurotrophic activity and identification as a member of the serine protease inhibitor gene family","volume":"90","author":"Steele","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0014-4835(91)90248-D","article-title":"PEDF: A pigment epithelium-derived factor with potent neuronal differentiative activity","volume":"53","author":"Chader","year":"1991","journal-title":"Exp. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.exer.2008.06.003","article-title":"PEDF-deficient mice exhibit an enhanced rate of retinal vascular expansion and are more sensitive to hyperoxia-mediated vessel obliteration","volume":"87","author":"Huang","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1042\/CS20130463","article-title":"PEDF and its roles in physiological and pathological conditions: Implication in diabetic and hypoxia-induced angiogenic diseases","volume":"128","author":"He","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.expneurol.2006.04.016","article-title":"Retinal pigment epithelial cell transplantation could provide trophic support in Parkinson\u2019s disease: Results from an in vitro model system","volume":"201","author":"McKay","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_36","first-page":"361","article-title":"Ranibizumab: Phase III Clinical Trial Results","volume":"19","author":"Rosenfeld","year":"2006","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1016\/j.ophtha.2013.03.046","article-title":"Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: A multicenter cohort study (SEVEN-UP)","volume":"120","author":"Rofagha","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1136\/bjo.2009.159160","article-title":"Ranibizumab (Lucentis) in neovascular age-related macular degeneration: Evidence from clinical trials","volume":"94","author":"Mitchell","year":"2010","journal-title":"Br. J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/j.1600-0854.2008.00734.x","article-title":"Exosome function: From tumor immunology to pathogen biology","volume":"9","author":"Schorey","year":"2008","journal-title":"Traffic"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.bcp.2011.12.037","article-title":"The multifaceted exosome: Biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities","volume":"83","author":"Pant","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.biocel.2012.08.007","article-title":"Exosomes: New players in cell-cell communication","volume":"44","author":"Bang","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Klingeborn, M., Dismuke, W.M., Skiba, N.P., Kelly, U., Stamer, W.D., and Bowes Rickman, C. (2017). Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-05102-9"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/978-3-319-75402-4_65","article-title":"Polarized exosome release from the retinal pigmented epithelium","volume":"1074","author":"Klingeborn","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Vautrot, V., Chanteloup, G., Elmallah, M., Cordonnier, M., Aubin, F., Garrido, C., and Gobbo, J. (2019). Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer. J. Oncol., 2019.","DOI":"10.1155\/2019\/8585276"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jcb.29120","article-title":"Exosomes: New insights into cancer mechanisms","volume":"121","author":"Sahebi","year":"2020","journal-title":"J. Cell. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1097\/MOH.0000000000000235","article-title":"Exosomes promote bone marrow angiogenesis in hematologic neoplasia: The role of hypoxia","volume":"23","author":"Ohyashiki","year":"2016","journal-title":"Curr. Opin. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.gpb.2015.02.001","article-title":"Exosome and exosomal microRNA: Trafficking, sorting, and function","volume":"13","author":"Zhang","year":"2015","journal-title":"Genom. Proteom. Bioinforma."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1093\/hmg\/9.20.3011","article-title":"V Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1","volume":"9","author":"Pizzigoni","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1001\/archopht.1976.03910040593001","article-title":"X-linked ocular albinism. An oculocutaneous macromelanosomal disorder","volume":"94","author":"Hambrick","year":"1976","journal-title":"Arch. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9055","DOI":"10.1073\/pnas.93.17.9055","article-title":"The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes","volume":"93","author":"Schiaffino","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","first-page":"5143","article-title":"Expression of OA1 limits the fusion of a subset of MVBs with lysosomes-a mechanism potentially involved in the initial biogenesis of melanosomes","volume":"126","author":"Burgoyne","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"McKay, B.S., Congrove, N.R., Johnson, A.A., Dismuke, W.M., Bowen, T.J., and Stamer, W.D. (2013). A role for myocilin in receptor-mediated endocytosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082301"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.exer.2006.09.020","article-title":"Myocilin-associated exosomes in human ocular samples","volume":"84","author":"Perkumas","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1001\/archophthalmol.2010.318","article-title":"Prevalence of age-related macular degeneration in the US population","volume":"129","author":"Klein","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.ajo.2013.06.004","article-title":"Associations of candidate genes to age-related macular degeneration among racial\/ethnic groups in the multi-ethnic study of atherosclerosis","volume":"156","author":"Klein","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_56","first-page":"1","article-title":"United States life tables, 2014","volume":"66","author":"Arias","year":"2017","journal-title":"Natl. Vital Stat. Rep."},{"key":"ref_57","first-page":"117","article-title":"Mammalian cones: Disc shedding, phagocytosis, and renewal","volume":"17","author":"Anderson","year":"1978","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_58","first-page":"31","article-title":"Cell death in age-related macular degeneration","volume":"5","author":"Adler","year":"1999","journal-title":"Mol. Vis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.preteyeres.2018.12.003","article-title":"On the origin of proteins in human drusen: The meet, greet and stick hypothesis","volume":"70","author":"Bergen","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1056\/NEJMra0801537","article-title":"Age-related macular degeneration","volume":"358","author":"Jager","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.pneurobio.2015.07.002","article-title":"Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson\u2019s disease","volume":"132","author":"Bastide","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.amjmed.2015.10.015","article-title":"Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration","volume":"129","author":"Brilliant","year":"2016","journal-title":"Am. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.ophtha.2003.11.010","article-title":"Risk factors for incident age-related macular degeneration: Pooled findings from 3 continents","volume":"111","author":"Tomany","year":"2004","journal-title":"Ophthalmology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/pcmr.12782","article-title":"Oral levodopa rescues retinal morphology and visual function in a murine model of human albinism","volume":"32","author":"Lee","year":"2019","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/ceo.12325","article-title":"Does levodopa improve vision in albinism? Results of a randomized, controlled clinical trial","volume":"42","author":"Summers","year":"2014","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Baba, K., Debruyne, J.P., and Tosini, G. (2017). Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-05394-x"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/910\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:16:36Z","timestamp":1760174196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,8]]},"references-count":66,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cells9040910"],"URL":"https:\/\/doi.org\/10.3390\/cells9040910","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,8]]}}}