Keck School Faculty

David R. Hinton, MD
David R. Hinton, MD
Professor of Pathology;Gavin S. Herbert Professorship in Vision Research;Associate Dean for Vision Science;Vice Chair of Pathology;Director, Dean's Research Scholars Program;Exam Committee Facilitator
Pathology
NRT 1450 Biggy Street Off Campus Los Angeles
Dr Hinton investigates the pathogenesis of blinding retinal diseases including age related macular degeneration (AMD) and proliferative vitreoretinopathy(PVR). In particular, he is interested in how alterations in the retinal microenvironment can promote the development of intraocular fibrosis, proliferative membranes and neovascular choroidal responses. His work has established the central role of the retinal pigment epithelial (RPE) cell in these disorders, and has demonstrated novel mechanisms for growth factor activation of the RPE with resulting alterations in migration, proliferation and gene expression. He has developed and validated several in vitro and in vivo models of PVR and choroidal neovascularization and has used these models to elucidate basic mechanisms of disease and to evaluate novel therapeutic approaches to the disorders. He is especially interested in therapeutic approaches involving manipulation of growth factor receptors and their intracellular signaling pathways. He has now extended this work into investigating genetic polymorphisms that result in susceptibility to these disorders in human populations. Most recently, Dr Hinton’s lab has been evaluating endogenous neuroprotectants (eg pigment epithelial derived factor) and chaperones (alpha B crystallin) for their therapeutic potential. He has also developed methods for differentiating RPE cells from human embryonic stem cells and is evaluating these cells for their potential for cellular therapy for patients with AMD. In a collaborative Program Project with investigators at the Cleveland Clinic, Dr Hinton investigates the immunopathogenesis of demyelinating diseases of the brain and spinal cord in animal models.

Mechanism of cytokinesis failure in ovarian cystadenomas with defective BRCA1 and P53 pathways Int J Cancer. 2018 Dec 01; 143(11):2932-2942. . View in PubMed

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells Graefes Arch Clin Exp Ophthalmol. 2018 Nov; 256(11):2113-2125. . View in PubMed

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells Graefes Arch Clin Exp Ophthalmol. 2018 Sep 13. . View in PubMed

Mechanism of cytokinesis failure in ovarian cystadenomas with defective brca1 and p53 pathways Int J Cancer. 2018 Jul 06. . View in PubMed

A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration Sci Transl Med. 2018 Apr 04; 10(435). . View in PubMed

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration Nat Med. 2018 Jan; 24(1):50-61. . View in PubMed

APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective TrialReport No. 2. Retina. 2017 Nov 22. . View in PubMed

Endoplasmic reticulum-mitochondrial crosstalk: a novel role for the mitochondrial peptide humanin Neural Regen Res. 2017 Jan; 12(1):35-38. . View in PubMed

Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models Stem Cells Int. 2017; 2017:9428176. . View in PubMed

Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium Int J Retina Vitreous. 2017; 3:41. . View in PubMed

Aqueous Angiography with Fluorescein and Indocyanine Green in Bovine Eyes Transl Vis Sci Technol. 2016 Nov; 5(6):5. . View in PubMed

An Innovative Surgical Technique for Subretinal Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium in Yucatan Mini Pigs: Preliminary Results Ophthalmic Surg Lasers Imaging Retina. 2016 Apr 01; 47(4):342-51. . View in PubMed

aB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition Am J Pathol. 2016 Apr; 186(4):859-73. . View in PubMed

Molecular mechanisms of subretinal fibrosis in age-related macular degeneration Exp Eye Res. 2016 Jan; 142:19-25. . View in PubMed

Humanin Protects RPE Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Upregulation of Mitochondrial Glutathione PLoS One. 2016; 11(10):e0165150. . View in PubMed

Differential Regulation of Self-reactive CD4+ T Cells in Cervical Lymph Nodes and Central Nervous System during Viral Encephalomyelitis Front Immunol. 2016; 7:370. . View in PubMed

Aqueous Angiography: Real-Time and Physiologic Aqueous Humor Outflow Imaging PLoS One. 2016; 11(1):e0147176. . View in PubMed

Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration Biochim Biophys Acta. 2016 Jan; 1860(1 Pt B):258-68. . View in PubMed

Aqueous Angiography-Mediated Guidance of Trabecular Bypass Improves Angiographic Outflow in Human Enucleated Eyes Invest Ophthalmol Vis Sci. 2016 09 01; 57(11):4558-65. . View in PubMed

Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination Glia. 2015 Nov; 63(11):2106-2120. . View in PubMed

Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis J Virol. 2015 Sep; 89(18):9299-312. . View in PubMed

Inhibition of DNA Methylation and Methyl-CpG-Binding Protein 2 Suppresses RPE Transdifferentiation: Relevance to Proliferative Vitreoretinopathy Invest Ophthalmol Vis Sci. 2015 Aug; 56(9):5579-89. . View in PubMed

Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination Glia. 2015 Jun 30. . View in PubMed

J Neuroinflammation. 2015 Apr 22; 12:79. . View in PubMed

Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis Immunology. 2015 Mar; 144(3):374-386. . View in PubMed

Attenuation of choroidal neovascularization by histone deacetylase inhibitor PLoS One. 2015; 10(3):e0120587. . View in PubMed

IL-18 is not therapeutic for neovascular age-related macular degeneration Nat Med. 2014 Dec; 20(12):1372-5. . View in PubMed

DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration Proc Natl Acad Sci U S A. 2014 Nov 11; 111(45):16082-7. . View in PubMed

Ceramide inhibits connective tissue growth factor expression by human retinal pigment epithelial cells Cytokine. 2014 Aug; 68(2):137-40. . View in PubMed

IL-27 limits central nervous system viral clearance by promoting IL-10 and enhances demyelination J Immunol. 2014 Jul 01; 193(1):285-94. . View in PubMed

Ifit2 deficiency results in uncontrolled neurotropic coronavirus replication and enhanced encephalitis via impaired alpha/beta interferon induction in macrophages J Virol. 2014 Jan; 88(2):1051-64. . View in PubMed

MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis ASN Neuro. 2013 Nov 26; 5(5):e00127. . View in PubMed

IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis J Neuroimmunol. 2013 Oct 15; 263(1-2):43-54. . View in PubMed

In vivo detection of hESC-RPE cells via confocal near-infrared fundus reflectance Ophthalmic Surg Lasers Imaging Retina. 2013 Jul-Aug; 44(4):380-4. . View in PubMed

Antiapoptotic properties of a-crystallin-derived peptide chaperones and characterization of their uptake transporters in human RPE cells Invest Ophthalmol Vis Sci. 2013 Apr 17; 54(4):2787-98. . View in PubMed

GRP78 plays an essential role in adipogenesis and postnatal growth in mice FASEB J. 2013 Mar; 27(3):955-64. . View in PubMed

Astrocyte-derived CXCL10 drives accumulation of antibody-secreting cells in the central nervous system during viral encephalomyelitis J Virol. 2013 Mar; 87(6):3382-92. . View in PubMed

Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis J Neuroinflammation. 2012 Dec 14; 9:269. . View in PubMed

Green tea polyphenols precondition against cell death induced by oxygen-glucose deprivation via stimulation of laminin receptor, generation of reactive oxygen species, and activation of protein kinase Ce J Biol Chem. 2012 Oct 05; 287(41):34694-708. . View in PubMed

Angiofibrotic response to vascular endothelial growth factor inhibition in diabetic retinal detachment: report no1. Arch Ophthalmol. 2012 Sep; 130(9):1127-34. . View in PubMed

Deficiency of aB crystallin augments ER stress-induced apoptosis by enhancing mitochondrial dysfunction Free Radic Biol Med. 2012 Sep 01; 53(5):1111-22. . View in PubMed

ERK1/2 activation is a therapeutic target in age-related macular degeneration Proc Natl Acad Sci U S A. 2012 Aug 21; 109(34):13781-6. . View in PubMed

Mesh-supported submicron parylene-C membranes for culturing retinal pigment epithelial cells Biomed Microdevices. 2012 Aug; 14(4):659-67. . View in PubMed

J Neuroinflammation. 2012 May 29; 9:104. . View in PubMed

DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88 Cell. 2012 May 11; 149(4):847-59. . View in PubMed

CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis J Virol. 2012 Mar; 86(5):2416-27. . View in PubMed

PLoS One. 2012; 7(7):e42088. . View in PubMed

Mechanism of RPE cell death in a-crystallin deficient mice: a novel and critical role for MRP1-mediated GSH efflux PLoS One. 2012; 7(3):e33420. . View in PubMed

A novel approach for subretinal implantation of ultrathin substrates containing stem cell-derived retinal pigment epithelium monolayer Ophthalmic Res. 2012; 48(4):186-91. . View in PubMed

A phase 1/2 study of orally administered synthetic hypericin for treatment of recurrent malignant gliomas Cancer. 2011 Nov 01; 117(21):4905-15. . View in PubMed

Methionine sulfoxide reductase A: Structure, function and role in ocular pathology World J Biol Chem. 2011 Aug 26; 2(8):184-92. . View in PubMed

CXCR3-dependent plasma blast migration to the central nervous system during viral encephalomyelitis J Virol. 2011 Jul; 85(13):6136-47. . View in PubMed

Antenatal maternal stress alters functional brain responses in adult offspring during conditioned fear Brain Res. 2011 Apr 18; 1385:163-74. . View in PubMed

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration Nature. 2011 Mar 17; 471(7338):325-30. . View in PubMed

Factors supporting intrathecal humoral responses following viral encephalomyelitis J Virol. 2011 Mar; 85(6):2589-98. . View in PubMed

Grp78 heterozygosity regulates chaperone balance in exocrine pancreas with differential response to cerulein-induced acute pancreatitis Am J Pathol. 2010 Dec; 177(6):2827-36. . View in PubMed

Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species J Neurosci Res. 2010 Dec; 88(16):3644-55. . View in PubMed

Enhanced antiviral T cell function in the absence of B7-H1 is insufficient to prevent persistence but exacerbates axonal bystander damage during viral encephalomyelitis J Immunol. 2010 Nov 01; 185(9):5607-18. . View in PubMed

aB crystallin is apically secreted within exosomes by polarized human retinal pigment epithelium and provides neuroprotection to adjacent cells PLoS One. 2010 Oct 08; 5(10):e12578. . View in PubMed

A comparison of hypoxia-inducible factor-a in surgically excised neovascular membranes of patients with diabetes compared with idiopathic epiretinal membranes in nondiabetic patients Retina. 2010 Oct; 30(9):1472-8. . View in PubMed

Aquaporin-1-mediated cerebral edema following traumatic brain injury: effects of acidosis and corticosteroid administration J Neurosurg. 2010 May; 112(5):1095-104. . View in PubMed

alphaB-crystallin regulation of angiogenesis by modulation of VEGF Blood. 2010 Apr 22; 115(16):3398-406. . View in PubMed

Expression and regulation of enzymes in the ceramide metabolic pathway in human retinal pigment epithelial cells and their relevance to retinal degeneration Vision Res. 2010 Mar 31; 50(7):643-51. . View in PubMed

Gamma interferon signaling in oligodendrocytes is critical for protection from neurotropic coronavirus infection J Virol. 2010 Mar; 84(6):3111-5. . View in PubMed

Identification of a novel sodium-coupled oligopeptide transporter (SOPT2) in mouse and human retinal pigment epithelial cells Invest Ophthalmol Vis Sci. 2010 Jan; 51(1):413-20. . View in PubMed

Attainment of polarity promotes growth factor secretion by retinal pigment epithelial cells: relevance to age-related macular degeneration Aging (Albany NY). 2009 Dec 27; 2(1):28-42. . View in PubMed

BMP4 mediates oxidative stress-induced retinal pigment epithelial cell senescence and is overexpressed in age-related macular degeneration J Biol Chem. 2009 Apr 03; 284(14):9529-39. . View in PubMed

Immunocytochemical analysis of retinal neurons under electrical stimulation Brain Res. 2009 Feb 19; 1255:89-97. . View in PubMed

A protocol for the culture and differentiation of highly polarized human retinal pigment epithelial cells Nat Protoc. 2009; 4(5):662-73. . View in PubMed

Memory CD4+ T-cell-mediated protection from lethal coronavirus encephalomyelitis J Virol. 2008 Dec; 82(24):12432-40. . View in PubMed

Connective tissue growth factor as a mediator of intraocular fibrosis Invest Ophthalmol Vis Sci. 2008 Sep; 49(9):4078-88. . View in PubMed

Endoplasmic reticulum stress induced by oxidative stress in retinal pigment epithelial cells Graefes Arch Clin Exp Ophthalmol. 2008 May; 246(5):677-83. . View in PubMed

CD4 T cells contribute to virus control and pathology following central nervous system infection with neurotropic mouse hepatitis virus J Virol. 2008 Mar; 82(5):2130-9. . View in PubMed

Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia Exp Eye Res. 2008 Feb; 86(2):355-65. . View in PubMed

alpha-Crystallin distribution in retinal pigment epithelium and effect of gene knockouts on sensitivity to oxidative stress Mol Vis. 2007 Apr 04; 13:566-77. . View in PubMed

In vivo models of proliferative vitreoretinopathy Nat Protoc. 2007; 2(1):67-77. . View in PubMed

Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis J Neurosci Res. 2006 Nov 01; 84(6):1225-34. . View in PubMed

Altered neuroantigen-specific cytokine secretion in a Th2 environment reduces experimental autoimmune encephalomyelitis J Neuroimmunol. 2006 Sep; 178(1-2):30-9. . View in PubMed

Mouse hepatitis virus pathogenesis in the central nervous system is independent of IL-15 and natural killer cells Virology. 2006 Jun 20; 350(1):206-15. . View in PubMed

Am J Pathol. 2006 May; 168(5):1722-36. . View in PubMed

Am J Pathol. 2006 May; 168(5):1722-36. . View in PubMed

MMP-2 and MMP-9 secretion by rpe is stimulated by angiogenic molecules found in choroidal neovascular membranes Retina. 2006 Apr; 26(4):454-61. . View in PubMed

CNS viral infection diverts homing of antibody-secreting cells from lymphoid organs to the CNS Eur J Immunol. 2006 Mar; 36(3):603-12. . View in PubMed

Inhibition of interferon-gamma signaling in oligodendroglia delays coronavirus clearance without altering demyelination Am J Pathol. 2006 Mar; 168(3):796-804. . View in PubMed

Characterization of brimonidine transport in retinal pigment epithelium Invest Ophthalmol Vis Sci. 2006 Jan; 47(1):287-94. . View in PubMed

Hepatocyte growth factor protects RPE cells from apoptosis induced by glutathione depletion Invest Ophthalmol Vis Sci. 2005 Nov; 46(11):4311-9. . View in PubMed

In vivo expression of GFP transgene delivered via a replicating feline leukemia virus Vet Microbiol. 2005 Oct 31; 110(3-4):181-95. . View in PubMed

Astrocyte expression of a dominant-negative interferon-gamma receptor J Neurosci Res. 2005 Oct 01; 82(1):20-31. . View in PubMed

Expression of a dominant negative IFN-gammareceptor on mouse oligodendrocytes Glia. 2005 Jul; 51(1):22-34. . View in PubMed

A selective cyclic integrin antagonist blocks the integrin receptors alphavbeta3 and alphavbeta5 and inhibits retinal pigment epithelium cell attachment, migration and invasion BMC Ophthalmol. 2005 Jun 29; 5:16. . View in PubMed

Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization Lab Invest. 2005 Jun; 85(6):721-33. . View in PubMed

Expression of matrix metalloproteinases and their tissue inhibitor during viral encephalitis J Virol. 2005 Apr; 79(8):4764-73. . View in PubMed

Long-term stimulation by active epiretinal implants in normal and RCD1 dogs J Neural Eng. 2005 Mar; 2(1):S65-73. . View in PubMed

Maintenance of CD8+ T cells during acute viral infection of the central nervous system requires CD4+ T cells but not interleukin-2 Viral Immunol. 2005; 18(1):162-9. . View in PubMed

Differential regulation of primary and secondary CD8+ T cells in the central nervous system J Immunol. 2004 Nov 15; 173(10):6265-73. . View in PubMed

Ceramide-induced apoptosis: role of catalase and hepatocyte growth factor Free Radic Biol Med. 2004 Jul 15; 37(2):166-75. . View in PubMed

Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy Diabetes Care. 2004 Mar; 27(3):758-64. . View in PubMed

Gene therapy in a murine model for clinical application to multiple sclerosis Ann Neurol. 2004 Mar; 55(3):390-9. . View in PubMed

Mouse strain-dependent heterogeneity of resting limbal vasculature Invest Ophthalmol Vis Sci. 2004 Feb; 45(2):441-7. . View in PubMed

Hepatocyte growth factor and its role in the pathogenesis of retinal detachment Invest Ophthalmol Vis Sci. 2004 Jan; 45(1):323-9. . View in PubMed

Developmental retinal apoptosis in Ku86-/- mice DNA Repair (Amst). 2003 Dec 09; 2(12):1429-34. . View in PubMed

A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization Arch Ophthalmol. 2003 Sep; 121(9):1283-8. . View in PubMed

Microphthalmia resulting from MSX2-induced apoptosis in the optic vesicle Invest Ophthalmol Vis Sci. 2003 Jun; 44(6):2404-12. . View in PubMed

Matrix metalloproteinase expression correlates with virulence following neurotropic mouse hepatitis virus infection J Virol. 2002 Aug; 76(15):7374-84. . View in PubMed

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