Abstract
Microglia, the principal resident immune cell in the retina, play constitutive roles in immune surveillance and synapse maintenance, and are also associated with retinal disease, including those occurring in the macula. Perspectives on retinal microglia function have derived largely from rodent models and how these relate to the macula-bearing primate retina is unclear. In this study, we examined microglial distribution and cellular morphology in the adult rhesus macaque retina, and performed comparative characterizations in three retinal locations along the center-to-periphery axis (parafoveal, macular, and the peripheral retina). We found that microglia density peaked in the parafoveal retina and decreased in the peripheral retina. Individual microglial morphology reflected macular specialization, with macular microglia demonstrating the largest and most complex dendritic arbors relative to other retinal locations. Comparing retinal microglia between young and middle-aged animals, microglial density increased in the macular, but not in the peripheral retina with age, while microglial morphology across all locations remained relatively unchanged. Our findings indicate that microglial distribution and morphology demonstrate regional specialization in the retina, correlating with gradients of other retinal cell types. As microglia are innate immune cells implicated in age-related macular diseases, age-related microglial changes may be related to the increased vulnerability of the aged macula to immune-related neurodegeneration.
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Acknowledgements
The authors are grateful to Dr. Peter MacLeish, Morehouse School of Medicine, Atlanta, GA, for the generous gift of the 7G6 antibody and to Dr. Paul Kaufman, Department of Ophthalmology & Visual Sciences, University of Wisconsin-Madison, for his guidance and encouragement. This work is supported by the National Eye Institute Intramural Research Program. J.S. is supported by the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. T.M.N. is supported by NIH NEI Core Grant P30 EY016665, Research to Prevent Blindness, the Wisconsin National Primate Research Center P51RR000167/P51OD011106, and the Retina Research Foundation Catherine and Latimer Murfee chair.
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JS, LZ, RNF, and WTW planned the experiments, JS and LZ conducted the experiments, TMN prepared materials for the experiments, JS and WTW wrote the manuscript. All authors reviewed the manuscript and provided critical comment.
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Singaravelu, J., Zhao, L., Fariss, R.N. et al. Microglia in the primate macula: specializations in microglial distribution and morphology with retinal position and with aging. Brain Struct Funct 222, 2759–2771 (2017). https://doi.org/10.1007/s00429-017-1370-x
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DOI: https://doi.org/10.1007/s00429-017-1370-x