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.

Characterization and Regulation of Carrier Proteins of Mitochondrial Glutathione Uptake in Human Retinal Pigment Epithelium Cells Invest Ophthalmol Vis Sci. 2019 Feb 01; 60(2):500-516. . View in PubMed

APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: Results of a Prospective TrialReport No. 2. Retina. 2019 Feb; 39(2):265-273. . 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

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

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

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

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

Advancing toxicology research using in vivo high throughput toxicology with small fish models ALTEX. 2016; 33(4):435-452. . 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

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

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

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

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

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

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

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

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

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

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

Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis Cell Death Differ. 2010 Mar; 17(3):488-98. . 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

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

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

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

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

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

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

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

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

Angiopoietin-1 upregulation by vascular endothelial growth factor in human retinal pigment epithelial cells Invest Ophthalmol Vis Sci. 2001 Jun; 42(7):1617-25. . View in PubMed

CD8 T cell mediated immunity to neurotropic MHV infection Adv Exp Med Biol. 2001; 494:299-308. . View in PubMed

Acute CNS infection is insufficient to mediate chronic T cell retention Adv Exp Med Biol. 2001; 494:349-54. . View in PubMed

Contributions of CD8+ T cells and viral spread to demyelinating disease J Immunol. 2000 Apr 15; 164(8):4080-8. . View in PubMed

Contributions of Fas-Fas ligand interactions to the pathogenesis of mouse hepatitis virus in the central nervous system J Virol. 2000 Mar; 74(5):2447-50. . View in PubMed

Activation of regulatory cells suppresses experimental allergic encephalomyelitis via secretion of IL-10 J Immunol. 1999 Dec 01; 163(11):6338-44. . View in PubMed

A distinct integrin-mediated phagocytic pathway for extracellular matrix remodeling by RPE cells Invest Ophthalmol Vis Sci. 1999 Oct; 40(11):2713-23. . View in PubMed

Antibody prevents virus reactivation within the central nervous system J Immunol. 1999 Jun 15; 162(12):7358-68. . View in PubMed

A functioning composite 'corticotroph' pituitary adenoma with interspersed adrenocortical cells Pituitary. 1999 May; 1(3-4):279-84. . View in PubMed

Cytologic features of secretory meningioma Acta Cytol. 1999 Mar-Apr; 43(2):121-5. . View in PubMed

Cellular response in subretinal neovascularization induced by bFGF-impregnated microspheres Invest Ophthalmol Vis Sci. 1999 Feb; 40(2):524-8. . View in PubMed

Excessively high prolactin level in a patient with a nonprolactin-secreting adenomaCase report. J Neurosurg. 1998 Dec; 89(6):1043-6. . View in PubMed

Advanced glycation end products in age-related macular degeneration Arch Ophthalmol. 1998 Dec; 116(12):1629-32. . View in PubMed

Cytologic features of hemangioblastoma: comparison with meningioma, anaplastic astrocytoma and renal cell carcinoma Acta Cytol. 1998 Sep-Oct; 42(5):1104-10. . View in PubMed

CTL effector function within the central nervous system requires CD4+ T cells J Immunol. 1998 Mar 15; 160(6):2896-904. . View in PubMed

Ability of retroviral transduction to modify the angiogenic characteristics of RPE cells Graefes Arch Clin Exp Ophthalmol. 1998 Mar; 236(3):220-9. . View in PubMed

Apoptosis in surgically excised choroidal neovascular membranes in age-related macular degeneration Arch Ophthalmol. 1998 Feb; 116(2):203-9. . View in PubMed

Apoptosis of JHMV-specific CTL in the CNS in the absence of CD4+ T cells Adv Exp Med Biol. 1998; 440:425-30. . View in PubMed

Chondromyxoid fibroma of the temporal bone Surg Neurol. 1997 Aug; 48(2):148-52. . View in PubMed

cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and migration of cultured bovine retinal pigment epithelial cells Invest Ophthalmol Vis Sci. 1997 Feb; 38(2):520-8. . View in PubMed

Characterization of spherical amyloid protein from a prolactin-producing pituitary adenoma Acta Neuropathol. 1997 Jan; 93(1):43-9. . View in PubMed

Acute polyneuropathy after high dose cytosine arabinoside in patients with leukemia Cancer. 1996 Nov 01; 78(9):1899-905. . View in PubMed

Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro Clin Cancer Res. 1996 May; 2(5):843-6. . View in PubMed

Cerebral neurocytoma: an unusual cause of refractory epilepsyCase report and review of the literature. Epilepsia. 1995 Dec; 36(12):1237-40. . View in PubMed

A new model of subretinal neovascularization in the rabbit Invest Ophthalmol Vis Sci. 1995 Sep; 36(10):2110-9. . View in PubMed

Effect of tecogalan sodium on angiogenesis in vitro by choroidal endothelial cells Invest Ophthalmol Vis Sci. 1995 May; 36(6):1076-83. . View in PubMed

Effect of intravitreal administration of indomethacin on experimental subretinal neovascularization in the subhuman primate Arch Ophthalmol. 1995 Feb; 113(2):222-6. . View in PubMed

Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells Invest Ophthalmol Vis Sci. 1994 Dec; 35(13):4253-9. . View in PubMed

Cytokine expression in radiation-induced delayed cerebral injury Neurosurgery. 1994 Nov; 35(5):822-9; discussion 829-30. . View in PubMed

Collagen gel contraction induced by retinal pigment epithelial cells and choroidal fibroblasts involves the protein kinase C pathway Curr Eye Res. 1994 Jun; 13(6):451-9. . View in PubMed

Dexamethasone induced proliferation of cultured retinal pigment epithelial cells Curr Eye Res. 1994 Apr; 13(4):257-61. . View in PubMed

Dural invasion by craniofacial and calvarial neoplasms: MR imaging and histopathologic evaluation Radiology. 1993 Sep; 188(3):747-9. . View in PubMed

Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen Neurosurgery. 1993 Mar; 32(3):485-9; discussion 489-90. . View in PubMed

Differential effects of tumor necrosis factor-alpha on proliferation, cell surface antigen expression, and cytokine interactions in malignant gliomas Neurosurgery. 1993 Jan; 32(1):85-94. . View in PubMed

Cytokines and immunoregulatory molecules in malignant glial neoplasms J Neurosurg. 1992 Aug; 77(2):265-73. . View in PubMed

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Dystrophin protein and RFLP analysis for fetal diagnosis and carrier confirmation of Duchenne muscular dystrophy Prenat Diagn. 1990 Nov; 10(11):703-15. . View in PubMed

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Assessment of visual impairment in patients with Alzheimer's disease Am J Ophthalmol. 1987 Aug 15; 104(2):113-20. . View in PubMed

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