Immune cells in the retina demonstrate significant dynamic motility that report on their physiology and function. We have examined the anatomy and behavior of ocular immune cells including 1. microglia in the retina, and 2. macrophages in the choroid. Our work employed ex vivo time-lapse confocal imaging techniques to visualize fluorescence-labeled microglia from transgenic CX3CR1+/GFP mice and follow dynamic microglia behavior in intact retinal and choroidal explants in real time. We used this technology to examine the aging changes in retinal microglia. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. We compared microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which probably compromise their ability to survey and interact with their environment continuously. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared with young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration. Choroidal macrophages are resident ocular immune cells capable of influencing the inflammatory environment of the outer retina and play a role in AMD pathogenesis. However, choroidal macrophages have not been characterized in detail in terms of their anatomy, distribution, behavior, and possible endogenous functions. We are currently involved in the following goals: 1.Characterize the anatomical distribution of macrophages in the adult mouse choroid 2.Describe the morphological features of choroidal macrophages and their physical associations with choroidal vessels at each level of the vascular tree 3.Examine the dynamic behavior of choroidal macrophages

National Institute of Health (NIH)
National Eye Institute (NEI)
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Kumar, Anil; Zhao, Lian; Fariss, Robert N et al. (2014) Vascular associations and dynamic process motility in perivascular myeloid cells of the mouse choroid: implications for function and senescent change. Invest Ophthalmol Vis Sci 55:1787-96
Toy, Brian C; Krishnadev, Nupura; Indaram, Maanasa et al. (2013) Drusen regression is associated with local changes in fundus autofluorescence in intermediate age-related macular degeneration. Am J Ophthalmol 156:532-42.e1
Ma, Wenxin; Coon, Steven; Zhao, Lian et al. (2013) A2E accumulation influences retinal microglial activation and complement regulation. Neurobiol Aging 34:943-60
Ma, Wenxin; Cojocaru, Radu; Gotoh, Norimoto et al. (2013) Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation. Neurobiol Aging 34:2310-21
Zhao, Lian; Ma, Wenxin; Fariss, Robert N et al. (2009) Retinal vascular repair and neovascularization are not dependent on CX3CR1 signaling in a model of ischemic retinopathy. Exp Eye Res 88:1004-13
Liang, Katharine J; Lee, Jung Eun; Wang, Yunqing D et al. (2009) Regulation of dynamic behavior of retinal microglia by CX3CR1 signaling. Invest Ophthalmol Vis Sci 50:4444-51
Lee, Jung Eun; Liang, Katharine J; Fariss, Robert N et al. (2008) Ex vivo dynamic imaging of retinal microglia using time-lapse confocal microscopy. Invest Ophthalmol Vis Sci 49:4169-76