Wai T. Wong, M.D., Ph.D.

Senior Investigator

Neuron-Glia Interactions in Retinal Disease Section

NEI

Building 6, Room 217
6 Center Drive
Bethesda, MD 20892-0606

301-496-7566

wongw@nei.nih.gov

Research Topics

Our research group, the Neuron-Glia Interactions in Retinal Diseases Section (NGIRDS), investigates the role of microglia, the resident immune cell of the retina, in normal physiological function and in the pathogenesis of retinal diseases. Of particular interest are retinal diseases in which age-related neuroinflammation features prominently, such as diabetic retinopathy and age-related macular degeneration (AMD), which are responsible for the majority of vision loss in the developed world. Key areas of focus are: 1) the role of microglia in the basic physiological function of the retina, and cell-cell interactions between microglia and other retinal cell types, 2) the aging phenotype of the retinal microglial cell, 3) the role of microglia in the pathogenesis of retinal disorders, and 4) translational research on microglial-based therapies in preclinical and proof-of-concept phase I/II clinical trials.

Our research group, the Neuron-Glia Interactions in Retinal Diseases Section (NGIRDS), investigates the role of microglia, the resident immune cell of the retina, in normal physiological function and in the pathogenesis of retinal diseases. Of particular interest are retinal diseases in which age-related neuroinflammation features prominently, such as age-related macular degeneration (AMD), which is responsible for the majority of vision loss in the developed world. Key areas of focus are: 1) the role of microglia in the basic physiological function of the retina, and cell-cell interactions between microglia and other retinal cell types, 2) the aging phenotype of the retinal microglial cell, 3) the role of microglia in the pathogenesis of retinal disorders, and 4) translational research on microglial-based therapies in preclinical and proof-of-concept phase I/II clinical trials.

Our laboratory has used a combination of ex vivo live-imaging techniques, in vitro studies, and animal models of disease to investigate the involvement of microglia in intercellular interactions with other retinal cell types under normal and pathological conditions. One key motivation is to understand how these cellular interactions undergo progressive change during senescence, resulting in age-related neuroinflammation that drive retinal disease pathogenesis. We are interested in discovering the molecular bases for these cellular interactions which allow the discovery of therapeutic targets directed at retinal microglia. The group is currently involved in a number of phase I/II trials using microglial inhibition as a treatment for age-related macular degeneration.

Biography

Dr. Wong received S.B degrees in Chemical Engineering and Biology from the Massachusetts Institute of Technology (M.I.T.) in 1994 and M.D., Ph.D. degrees from Washington University of Medicine in 2001. His graduate thesis under Dr. Rachel Wong examined the role of neurotransmission in the developing retina in generating patterns of spontaneous retinal activity and remodeling retinal ganglion cell dendrites during the time of developmental synaptogenesis. He also performed postdoctoral work in the laboratory of Dr. Jean Bennett studying the developmental role of PEDF using gene therapy techniques. He completed an ophthalmology residency program at the University of Pennsylvania in 2005, and a medical retina fellowship at the National Eye Institute under Dr. Emily Chew in 2007. In 2007, he joined the Clinician Scientist Development Program at NEI and became a tenure track investigator in 2011, receiving tenure in 2017. A board-certified ophthalmologist and a member of the Macula Society, Dr. Wong specializes in diseases of the retina including age-related macular degeneration, diabetic retinopathy, and ocular von Hippel-Lindau disease, and conducts clinical research in the NIH Clinical Center. His laboratory, the Neuron-Glia Interactions in Retinal Diseases Section (NGIRDS), studies the role of microglia, the resident immune cell of the retina, in the pathogenesis of retinal diseases and the use of microglia-directed therapies.

Selected Publications

  1. Silverman SM, Ma W, Wang X, Zhao L, Wong WT. C3- and CR3-dependent microglial clearance protects photoreceptors in retinitis pigmentosa. J Exp Med. 2019;216(8):1925-1943.

  2. Ma W, Silverman SM, Zhao L, Villasmil R, Campos MM, Amaral J, Wong WT. Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization. Elife. 2019;8.

  3. Silverman SM, Wong WT. Microglia in the Retina: Roles in Development, Maturity, and Disease. Annu Rev Vis Sci. 2018;4:45-77.

  4. Zhang Y, Zhao L, Wang X, Ma W, Lazere A, Qian HH, Zhang J, Abu-Asab M, Fariss RN, Roger JE, Wong WT. Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation. Sci Adv. 2018;4(3):eaap8492.

  5. Zhao L, Zabel MK, Wang X, Ma W, Shah P, Fariss RN, Qian H, Parkhurst CN, Gan WB, Wong WT. Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. EMBO Mol Med. 2015;7(9):1179-97.


This page was last updated on August 21st, 2019