301 E. Muhammad Ali Boulevard, Louisville KY 40202
Telephone: 502-852-5466 Fax: 502-852-8550
Columbia University, New York, NY, AB, 06/1964 – Pre-Medicine
Cornell Medical School, New York, NY, MD, 6/1968 – Medicine
University of Texas Medical School, Dallas, TX, Fellowship, 06/1974 – Immunology
University of Iowa Hospitals & Clinics, Iowa City, IA, Residency, 6/1978 – Ophthalmology
Medical College of Wisconsin, Milwaukee, WI, Fellowship, 6/1979 – Retina
I have a novel background as a clinician scientist with scientific expertise in immunology and clinical expertise in vitreo-retinal diseases. My postdoctoral training at the University of Texas at Southwestern Medical School under the mentorship of J Wayne Streilein and Ruppert Billingham launched my interest in autoimmune diseases of the eye and led to the discovery of anterior chamber-associated immune deviation (ACAID). My clinical interest in uveitis has led to my research in ocular immunology and autoimmune diseases which has been funded by the NEI for past 30 years. Subsequently, my clinical training in retinal diseases was obtained under the tutelage of Thomas M Aaberg at the Medical College of Wisconsin. My interest in retinal diseases has involved the study of the pathogenesis and treatment of both age-related macular degeneration and hereditary retinal diseases. Many novel observations and insights were made in collaboration with many different colleagues, including the first successful submacular surgery to recover central vision in the presumed ocular histoplasmosis syndrome (POHS); the development of techniques to harvest and transplant sheets of RPE cells into the subretinal space of man and other species; the first clinical trial of human allogenic RPE cell transplantation in patients with exudative age-related macular degeneration (AMD) in the United States; the role of senescent Bruch’s membrane in RPE attachment and differentiation; the study of RPE cell differentiation and dedifferentiation in vitro. We are now involved in identifying novel therapies for Retinitis Pigmentosa (RP) using a mini swine model of the most common form of autosomal dominant RP, a Pro23His mutation in RHO, investigating stem cell therapy, gene therapy and neuroprotection.
Positions and Honors
Positions and Employment
1974-75 Assistant Professor, Department of Cell Biology, University Texas (Southwestern) Medical School, Dallas, TX
1979-84 Associate Professor, Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
1984-88 Professor & Director of Research, Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
1988-2000 Professor of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO
1988-1998 Chairman, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO
2000 – Chairman, Department of Ophthalmology and Visuals Sciences, University of Louisville School of Medicine; Director, Kentucky Lions Eye Center, Louisville, KY
Other Experience and Professional Memberships
1982- American Uveitis Society
1985-1989 Visual Disorders Study Section A-1 (Member)
National Eye Institute, National Institutes of Health
1987-1989, Chairman, Visual Disorders Study Section A-1
1992- Ocular Immunology and Inflammation
1998- 2008, Editor-in-Chief
2011 Consultant: California Institute of Regenerative Medicine
2011 Consultant: FDA Cellular, Tissue and Gene Therapies Advisory Committee Washington, DC – June 29, 2011
2011- Translational Vision Science and Technology, Associate Editor, Association for Research in Vision and Ophthalmology
2015 Consultant: FDA Cellular, Tissue and Gene Therapies Advisory Committee
1984 Designated the Olga Keith Weiss Scholar; Research to Prevent Blindness, Inc.
1987 Recipient of the Alcon Research Institute’s Scientific Award
2010 Gold Fellow ARVO
Contribution to Science
Immune privilege within the Anterior Chamber of the Eye
My research career in immunology was launched by my identification of a phenomenon subsequently known as anterior chamber-associated immune deviation (ACAID) with J. Wayne Streilein. The presence of immune privilege in the eye was then studied by us, as well as many other scientists and laboratories, and resulted in the recognition that it existed not because of sequestration from the host immune system but rather from distinctive immune regulatory mechanisms. The primary purpose of this phenomenon appears to be protection of the sensitive structures of the eye from infection without the potential destructive effects of cell-mediated immunity. Some of the novel mechanisms identified by my collaborators and me concerning immune privilege are:
- Kaplan, H.J., Streilein, J.W.: Immune response to immunization via the anterior chamber of the eye.II. An analysis of F1 lymphocyte-induced immune deviation. J. Immunol. 120:689-693, 1978. PMID: 632581,
- Waldrep, J.C., Kaplan, H.J.: Anterior chamber associated immune deviation induced by TNP-splenocytes (TNP-ACAID). II. Suppressor T cell networks. Invest. Ophthalmol. Vis. Sci. 24:1339-1345, 1983. PMID: 6225745.
- Ferguson, T.A., Waldrep, J.C., Kaplan, H.J.: The immune response and the eye. II. The nature of T suppressor cell induction in anterior chamber-associated immune deviation (ACAID). J. Immunol. 139:352-357, 1987. PMID: 2955039.
- Ferguson, T.A., Mahendra, S.L., Hooper, P., Kaplan, H.J.: The wavelength of light governing intraocular immune reactions. Invest. Ophthalmol. Vis. Sci. 33:1788-1795, 1992. PMID: 1550779.
Role of complement in the Eye
Although complement components were recognized to be present in the normal murine eye, as well as in induced intraocular inflammation (i.e. experimental autoimmune uveitis – EAU), there role and regulation was unknown. We were the first to show the expression of complement regulatory proteins (CRPs) in the normal murine eye, as well as the importance of these proteins in preventing autoimmune uveitis and in the induction of tolerance. Our studies also demonstrated experimentally that the alternate pathway of complement was important in the generation of laser-induced choroidal neovascularization, just prior to identification of the genetic importance of Factors H and B and other CRPs.
- Sohn, J.-H., Kaplan, H.J., Suk, H.-J., Bora, P.S., Bora, N.S.: Complement regulatory activity of normal human intraocular fluid is mediated by MCP, DAF and CD49. Ophthalmol. Vis. Sci. 41:4195-4202, 2000. PMID: PMC 1821086.
- Sohn, J.-H., Bora, P.S., Suk, H.-J., Molina, H., Kaplan, H.J., Bora, N.S.: Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat. 9(2):206-212, 2003.PMID: PMC 1821085.
- Jha, P., Sohn, J.H., Xu, Q., Nishihori, H., Wang, Y., Nishihori, S., Manickam, B., Kaplan, H.J., Bora, P.S., Bora, N.S.: The complement system plays a critical role in the development of experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 47(3):1030-8, 2006. PMCID: PMC 1975680.
- Bora, N.S., Kaliappan, S., Jha, P., Xu, Q., Sohn, J.H., Dhaulakhandi, D.B., Kaplan, H.J., Bora, P.S.: Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H. J. Immunol. 177(3):1872-8, 2006. PMID: 1985467.
Development of submacular surgery
Prior to the development of pharmacologic agents in the treatment of choroidal neovascularization (CNV) the mainstay of treatment was laser photocoagulation. Even subfoveal CNV membranes were treated with Argon laser despite even though loss of central vision would occur immediately with treatment. As a consequence of this suboptimal treatment we identified the first successful use of submacular surgery for the treatment of subfoveal CNV in the presumed ocular histoplasmosis syndrome (POHS). This surgical approach was very helpful for this subset of patients with CNV and allowed us, and others, to gain many new important insights into CNV in AMD.
- Thomas, M.A., Kaplan, H.J.: Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome. J. Ophthalmol. 111:1-7, 1991. PMID: 1985467.
- Desai, V.N., Del Priore, L.V., Kaplan, H.J.: Choriocapillaris atrophy after submacular surgery in the presumed ocular histoplasmosis syndrome. Ophthalmol. 113:408-09, 1995. PMID: 7710384.
- Reddy, V., Zamora, R., Kaplan, H.J.: Distribution of growth factors in subfoveal neovascular membranes in age related macular degeneration and presumed ocular histoplasmosis syndrome. J. Ophthalmol. 120:291-301, 1995. PMID: 7661200.
- Berger, A.S., Conway, M., Del Priore, L.V., Walker, R.S., Pollack, J.S., Kaplan, H.J.: Submacular surgery for subfoveal choroidal neovascular membranes in patients with presumed ocular histoplasmosis. Ophthalmol. 115:991-996, 1997. PMID: 9258220.
Immune regulation in experimental autoimmune uveitis (EAU)
My interest in autoimmune uveitis stemmed from my initial identification of ACAID with J Wayne Streilein. My collaboration with many colleagues allowed us to generate a model of acute anterior uveitis to a collagen peptide bound to melanin within the eye, the study of T regulatory (i.e. suppressor) cells and many other features of immune regulation in EAU.
- Cui Y, Shao H, Sun D, Kaplan HJ: Regulation of interphotoreceptor retinoid-binding protein (IRBP)-specific Th1 and Th17 cells in anterior chamber-associated immune deviation (ACAID). Invest Ophthalmol Vis Sci. 2009, Dec;50(12):5811-7. PMID: PMC 3275438.
- Jiang G, Sun D, Yang H, Lu Q, Kaplan HJ, Shao H: HMGB1 is an early and critical mediator in an animal model of uveitis induced by IRBP-specific T cells. J Leukoc Biol. 2014;95(4): 599-607. PMID: PMC 3958740.
- Liang D, Zuo A, Shao H, Chen M, Kaplan HJ, Sun D: Anti-inflammatory or proinflammatory effect of an adenosine receptor agonist on the Th17 autoimmune response is inflammatory environment-dependent. J Immuno. 2014:193(11):5498-505. PMCID: PMC 4299924.
- Ke Y, Sun D, Jiang G, Kaplan HJ, Shao H. IL-22-induced regulatory CD11b+ APCs suppress experimental autoimmune uveitis. J Immunol. 2011 Sep 1;187(5):2130-9. Epub 2011 Jul 27. PMID: PMC 3197698.
Retinal transplantation in retinal degeneration
As a vitreoretinal surgeon and scientist I have had a career long interest in retinal regeneration as a therapeutic tool in hereditary retinal degeneration (i.e. Retinitis Pigmentosa – RP) and age-related macular degeneration (AMD). We have pursued RPE and photoreceptor transplantation in patients, as well as developed a pig model of autosomal dominant Pro23His RP, the most common form of RP in North America. We have most recently conducted studies using transplantation of rod-derived pig iPSCs, as well as pig fetal retinal progenitors cells, to rescue cone photoreceptors in our pig model.
- Zhou L, Wang W, Liu Y, de Castro JF, Ezashi T, Telugu BP, Roberts RM, Kaplan HJ, Dean DC: Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells. 2011 June;29(6):972-80. PMID: PMC 4263955.
- Wang W, Zhou L, Lee SJ, Liu Y, Fernandez de Castro J, Emery D, Vukmanic E, Kaplan HJ, Dean DC: Swine cone and rod precursors arise sequentially and display sequential and transient integration and differentiation potential following transplantation. Invest Ophthalmol Vis Sci. 2014;55(1):301-9. PMID: PMC 3894797.
- Fernandez de Castro JP, Scott PA, Fransen JW, Demas J, DeMarco PJ, Kaplan HJ, McCall MA. Cone photoreceptors develop normally in the absence of functional rod photoreceptors in a transgenic swine model of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Apr 17;55(4):2460-8. PMID: 24618325.
- Wang W, Lee SJ, Scott PA, Lu X1, Emery D, Liu Y, Ezashi T, Roberts MR, Ross JW, Kaplan HJ, Dean DC: Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa. Cell Rep. 2016 Apr 12;15(2):372-85. PMID: 27050517.
Ongoing Research Support
1RP1EY024051 (Shao, PI; Kaplan, PI) 12/1/2014 – 11/30/2018
The Danger Signals in Autoimmune Uveitis
The role of danger signals (DAMPS), like HMGB1, in the induction of autoimmune uveitis is not well defined. The goal of this grant is to study the signaling pathways triggered by DAMPS to identify novel therapeutic targets for the treatment of autoimmune uveitis.
1R21EY025408 (Shao, PI; Kaplan, PI) 4/1/15 – 3/31/17
Exosomes Derived From Retinal Astrocytes in the Regulation of Retinal Vasculature
A major cause of blindness in children born prematurely is retinopathy of prematurity (ROP). Retinal angiogenesis is aberrant in ROP and the role of retinal astrocytes in development of the normal retinal vasculature is important. The contribution of retinal astrocytes to the aberrant angiogenesis in ROP is being studied.
W81XWH-14-2-0163 (Dean, PI; Kaplan, PI) 9/22/2014 – 9/21/2017
DOD – Vision Restoration with Granulocyte Colony-Stimulating Factor (GCSF)
Retinal damage from blast injuries to soldiers in combat has become a significant cause of visual disability. The goal of this project is to study the ability of GCSF to stimulate retinal photoreceptor degeneration following blast injuries in a rodent model.
Completed Research Support
R21EY020647-01A1 (Kaplan, PI) 12/1/2010-11/30/2013
Expansion of the Pro23His rhodopsin transgenic mini swine model of Retinitis Pigmentosa.
Following the clinical characterization of this model, the colony was expanded to allow collaborative studies with swine induced pluripotent stem cells (iPSC), swine embryonic retinal cells, as well as human ESC to rescue cone photoreceptors.