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AMD, Retinal Pigment Epithelium, GPR143, albinism, pigmentation, L-DOPA, GPCR

Biography

My research on the biology of RPE cells, and especially their pigmentation, has been ongoing since my graduate studies in the 1990s. As the principal investigator on this ‘multipartite’ application I bring my experience at successfully participating in and leading multidisciplinary groups toward a common goal. For example, I participated in the international Spheramine clinical trials (NCT00206687, BAY865280) in which cultured fetal human RPE were produced as tissue-type monolayers on small crosslinked gelatin beads, then surgically implanted in the brains of patients with Parkinson’s disease. The basis of this procedure is that all pigmented cells release L-DOPA, which is produced as a byproduct of melanin synthesis. During this research, where I tested many batches of RPE cultures for trophic activity and L-DOPA production, it became very clear that RPE pigmentation was the key factor in determining their trophic potential. I participated as a member of the team in this study from 2005-2009, my role was to culture RPE cells on beads and characterize them for numerous activities that would be either beneficial or detrimental when implanted into a patient’s brain. Upon closure of the stage two trial, I turned my attention to probing the linkage between pigmentation and RPE neurotrophic activity. This focus led to my identification of the L-DOPA receptor expressed by RPE, GPR143, and the downstream signaling activities of the receptor. We illustrated RPE exosome release as a primary event tied to GPR143 signaling, GPR143 signaling halts RPE exosome release. Exosomes drive angiogenesis and are likely to participate in the angiogenic disease process of neovascular AMD. We then asked whether AMD patients benefitted from L-DOPA supplementation. The question was simple, but required me to establish and lead a new team of collaborators. I met potential collaborators at ARVO, a made a lot of cold phone calls to develop a new team, most of whom I had never met. In the end, I brought together a team of 13 new collaborators to ask, ‘are patients prescribed L-DOPA protected from AMD?’. The answer was yes. This led me to establish a new team of local clinicians to prospectively test whether L-DOPA treatment benefits patients with AMD. Again, the answer was yes. However, developing and leading this team, on an unfunded study that directly confronts an AMD clinicians’ earnings, was not trivial, and demonstrates both my commitment and my leadership skills. We successfully completed and published this study, the first showing the GPR143 signaling may be beneficial for patients with AMD. Significant more needs to be done before it will be ready for broad use, but we did show the pathway. In the proposal here, we ask a new and novel question, ‘how does zinc absorption from the diet, transport to RPE, and accumulation in pigment granules controlled by GPR143 signaling, affect AMD? Zinc was identified beneficial to a subset of people in the AREDs trials, but the detailed mechanism remains unexplored.

Activities

Employment (2)

The University of Arizona: Tucson, AZ, US

2002-10-01 to present | Professor (Ophthalmology and Vision Science)
Employment
Source: Self-asserted source
Brian S McKay

Duke University: Durham, NC, US

1997-07-01 to 2002-09-30 | Assistant Professor (Ophthalmology)
Employment
Source: Self-asserted source
Brian S McKay

Education and qualifications (2)

The Scripps Research Institute: La Jolla, CA, US

1995-01-02 to 1997-06-30 | PostDoc (Molecular and Experimental Medicine)
Education
Source: Self-asserted source
Brian S McKay

Medical College of Wisconsin: Milwaukee, WI, US

1990 to 1995 | Ph.D. (Cell Biology)
Education
Source: Self-asserted source
Brian S McKay

Professional activities (1)

Association for Research in Vision and Ophthalmology: Md., Md., US

1997-06-01 to present | Regular (Retinal Cell Biology)
Membership
Source: Self-asserted source
Brian S McKay

Funding (2)

RPE Trophic Activity for Retinal Protection

2017-03 to 2022-02 | Grant
National Eye Institute (Md., Md., US)
GRANT_NUMBER:

R01 EY026544-01

Source: Self-asserted source
Brian S McKay

OA1 Signaling and AMD

2010-04-01 to 2012-05-31 | Grant
BrightFocus Foundation (Clarksburg, US)
GRANT_NUMBER:

M2010074

Source: check_circle
ProposalCentral

Works (43)

Long Interspersed Nuclear Element-1 Analytes in Extracellular Vesicles as Tools for Molecular Diagnostics of Non-Small Cell Lung Cancer

International Journal of Molecular Sciences
2024-01-18 | Journal article
Contributors: Emma C. Bowers; Alexandre M. Cavalcante; Kimberly Nguyen; Can Li; Yingshan Wang; Randa El-Zein; Shu-Hsia Chen; Min P. Kim; Brian S. McKay; Kenneth S. Ramos
Source: check_circle
Crossref
grade
Preferred source (of 2)‎

Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration

Ophthalmology Retina
2023-09 | Journal article
Contributors: Max J. Hyman; Dimitra Skondra; Nitika Aggarwal; John Moir; Nick Boucher; Brian S. McKay; Mathew W. MacCumber; Jeremy A. Lavine
Source: check_circle
Crossref

Zinc Supplementation Induced Transcriptional Changes in Primary Human Retinal Pigment Epithelium: A Single-Cell RNA Sequencing Study to Understand Age-Related Macular Degeneration.

Cells
2023-02-28 | Journal article
Contributors: Emri E; Oisín Cappa; Kelly C; Elod Kortvely; SanGiovanni JP; McKay BS; Bergen AA; David Simpson; Imre Lengyel
Source: Self-asserted source
Brian S McKay

LINE-1 Cargo and Reverse Transcriptase Activity Profiles in Extracellular Vesicles from Lung Cancer Cells and Human Plasma.

International journal of molecular sciences
2022-03-22 | Journal article
Contributors: Bowers EC; Alexandre J. Motta; Kenneth S Knox; McKay BS; Ramos KS
Source: Self-asserted source
Brian S McKay

Levodopa Positively Affects Neovascular Age-Related Macular Degeneration.

The American journal of medicine
2020-07-03 | Journal article
Contributors: Anna G. Figueroa; Boyd BM; Cory A. Christensen, DO, MPH; Javid CG; McKay BS; Fagan TC; Snyder RW
Source: Self-asserted source
Brian S McKay

A G-Protein Coupled Receptor and Macular Degeneration.

Cells
2020-04-08 | Journal article
Contributors: Anna G. Figueroa; McKay BS
Source: Self-asserted source
Brian S McKay
grade
Preferred source (of 2)‎

Pigmentation and vision: Is GPR143 in control?

Journal of Neuroscience Research
2019-01 | Journal article
Contributors: Brian S. McKay
Source: check_circle
Crossref

GPR143 Signaling and Retinal Degeneration.

Advances in experimental medicine and biology
2019-01-01 | Journal article
Contributors: Figueroa AG; McKay BS
Source: Self-asserted source
Brian S McKay

Alzheimer's associated amyloid and tau deposition co-localizes with a homeostatic myelin repair pathway in two mouse models of post-stroke mixed dementia.

Acta neuropathologica communications
2018-09 | Journal article
Contributors: Nguyen TV; Hayes M; Zbesko JC; Frye JB; Congrove NR; Belichenko NP; McKay BS; Longo FM; Doyle KP
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Liquefaction of the Brain following Stroke Shares a Similar Molecular and Morphological Profile with Atherosclerosis and Mediates Secondary Neurodegeneration in an Osteopontin-Dependent Mechanism.

eNeuro
2018-09 | Journal article
Contributors: Chung AG; Frye JB; Zbesko JC; Constantopoulos E; Hayes M; Figueroa AG; Becktel DA; Antony Day W; Konhilas JP; McKay BS et al.
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Liquefaction of the brain following stroke shares a similar molecular and morphological profile with atherosclerosis and mediates secondary neurodegeneration in an osteopontin dependent mechanism

2018-02 | Other
OTHER-ID:

PPR18661

Contributors: Chung AG; Frye JB; Zbesko JC; Constantopoulos E; Hayes M; Figueroa AG; Becktel DA; Day WA; Konhilas JP; McKay BS et al.
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Comment on "Identification of Novel G Protein-Coupled Receptor 143 Ligands as Pharmacologic Tools for Investigating X-Linked Ocular Albinism".

Investigative ophthalmology & visual science
2017-09 | Journal article
Contributors: McKay BS; Lynch RM; Stamer WD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Pigmentation and Macular Degeneration: Is There a Role for GPR143?

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
2016-01 | Journal article
Contributors: McKay BS; Schwartz SG
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration.

The American journal of medicine
2015-10 | Journal article
Contributors: Brilliant MH; Vaziri K; Connor TB; Schwartz SG; Carroll JJ; McCarty CA; Schrodi SJ; Hebbring SJ; Kishor KS; Flynn HW et al.
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Controlled exosome release from the retinal pigment epithelium in situ.

Experimental eye research
2014-10 | Journal article
Contributors: Locke CJ; Congrove NR; Dismuke WM; Bowen TJ; Stamer WD; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Does levodopa improve vision in albinism? Results of a randomized, controlled clinical trial.

Clinical & experimental ophthalmology
2014-05 | Journal article
Contributors: Summers CG; Connett JE; Holleschau AM; Anderson JL; De Becker I; McKay BS; Brilliant MH
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

A role for myocilin in receptor-mediated endocytosis.

PloS one
2013-12 | Journal article
Contributors: McKay BS; Congrove NR; Johnson AA; Dismuke WM; Bowen TJ; Stamer WD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Myocilin, a component of a membrane-associated protein complex driven by a homologous Q-SNARE domain.

Biochemistry
2012-04 | Journal article
Contributors: Dismuke WM; McKay BS; Stamer WD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

PEDF and VEGF-A output from human retinal pigment epithelial cells grown on novel microcarriers.

Journal of biomedicine & biotechnology
2012-04 | Journal article
Contributors: Falk T; Congrove NR; Zhang S; McCourt AD; Sherman SJ; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

L-DOPA is an endogenous ligand for OA1.

PLoS biology
2008-09 | Journal article
Contributors: Lopez VM; Decatur CL; Stamer WD; Lynch RM; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina.

Biochimica et biophysica acta
2007-06 | Journal article
Contributors: Yu L; Kelly U; Ebright JN; Malek G; Saloupis P; Rickman DW; McKay BS; Arshavsky VY; Bowes Rickman C
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Enhanced accumulation of A2E in individuals homozygous or heterozygous for mutations in BEST1 (VMD2).

Experimental eye research
2007-03 | Journal article
Contributors: Bakall B; Radu RA; Stanton JB; Burke JM; McKay BS; Wadelius C; Mullins RF; Stone EM; Travis GH; Marmorstein AD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Myocilin-associated exosomes in human ocular samples.

Experimental eye research
2006-11 | Journal article
Contributors: Perkumas KM; Hoffman EA; McKay BS; Allingham RR; Stamer WD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Coiled-coil targeting of myocilin to intracellular membranes.

Experimental eye research
2006-09 | Journal article
Contributors: Stamer WD; Perkumas KM; Hoffman EA; Roberts BC; Epstein DL; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Retinal pigment epithelial cell transplantation could provide trophic support in Parkinson's disease: results from an in vitro model system.

Experimental neurology
2006-06 | Journal article
Contributors: McKay BS; Goodman B; Falk T; Sherman SJ
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Alterations in human trabecular meshwork cell homeostasis by selenium.

Experimental eye research
2005-11 | Journal article
Contributors: Conley SM; McKay BS; Gandolfi AJ; Stamer WD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Ca++-switch induction of RPE differentiation.

Experimental eye research
2005-11 | Journal article
Contributors: Rak DJ; Hardy KM; Jaffe GJ; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Barriers to productive transfection of trabecular meshwork cells.

Molecular vision
2005-10 | Journal article
Contributors: Hoffman EA; Conley SM; Stamer WD; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Extracellular trafficking of myocilin in human trabecular meshwork cells.

The Journal of biological chemistry
2005-06 | Journal article
Contributors: Hardy KM; Hoffman EA; Gonzalez P; McKay BS; Stamer WD
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Effect of NF-kappa B inhibition on TNF-alpha-induced apoptosis in human RPE cells.

Investigative ophthalmology & visual science
2004-07 | Journal article
Contributors: Yang P; McKay BS; Allen JB; Jaffe GJ
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Aquaporin-1 channels in human retinal pigment epithelium: role in transepithelial water movement.

Investigative ophthalmology & visual science
2003-06 | Journal article
Contributors: Stamer WD; Bok D; Hu J; Jaffe GJ; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Effect of mutant IkappaB on cytokine-induced activation of NF-kappaB in cultured human RPE cells.

Investigative ophthalmology & visual science
2003-03 | Journal article
Contributors: Yang P; McKay BS; Allen JB; Roberts WL; Jaffe GJ
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Cell-cell adhesion molecules and the development of an epithelial phenotype in cultured human retinal pigment epithelial cells.

Experimental eye research
1997-11 | Journal article
PMID: 9367646
Contributors: McKay BS; Irving PE; Skumatz CM; Burke JM
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Cell association increases RPE outgrowth from primary explant.

Current eye research
1997-09 | Journal article
PMID: 9288450
Contributors: McKay BS; Burke JM
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Molecular requirements for assembly and function of a minimized human integrin alphaIIbbeta3.

The Journal of biological chemistry
1996-11 | Journal article
PMID: 8940024
Contributors: McKay BS; Annis DS; Honda S; Christie D; Kunicki TJ
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Phenotypic heterogeneity of retinal pigment epithelial cells in vitro and in situ.

Experimental eye research
1996-01 | Journal article
PMID: 8674514
Contributors: Burke JM; Skumatz CM; Irving PE; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Separation of phenotypically distinct subpopulations of cultured human retinal pigment epithelial cells.

Experimental cell research
1994-07 | Journal article
PMID: 7517370
Contributors: McKay BS; Burke JM
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

The response of cultured human retinal pigment epithelium to hypoxia: a comparison to other cell types.

Investigative ophthalmology & visual science
1994-05 | Journal article
PMID: 8188480
Contributors: Nash RW; McKay BS; Burke JM
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

In vitro aging of bovine and human retinal pigment epithelium: number and activity of the Na/K ATPase pump.

Experimental eye research
1993-07 | Journal article
PMID: 8405172
Contributors: Burke JM; McKay BS
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Modulation of potassium transport in cultured retinal pigment epithelium and retinal glial cells by serum and epidermal growth factor.

Experimental cell research
1992-11 | Journal article
PMID: 1330655
Contributors: Arrindell EL; McKay BS; Jaffe GJ; Burke JM
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Collagen shield delivery of tissue plasminogen activator: functional and pharmacokinetic studies of anterior segment delivery.

Refractive & corneal surgery
1992-01 | Journal article
PMID: 1554639
Contributors: Murray TG; Jaffe GJ; McKay BS; Han DP; Burke JM; Abrams GW
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Retinal pigment epithelial cells of the posterior pole have fewer Na/K adenosine triphosphatase pumps than peripheral cells.

Investigative ophthalmology & visual science
1991-06 | Journal article
PMID: 1647375
Contributors: Burke JM; McKay BS; Jaffe GJ
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Intravitreal clearance of tissue plasminogen activator in the rabbit.

Archives of ophthalmology (Chicago, Ill. : 1960)
1988-07 | Journal article
PMID: 3134000
Contributors: Jaffe GJ; Green GD; McKay BS; Hartz A; Williams GA
Source: Self-asserted source
Brian S McKay via Europe PubMed Central

Peer review (3 reviews for 2 publications/grants)

Review activity for Molecular brain (1)
Review activity for Ophthalmology science. (2)