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M. R. Damani, A. M. Fontainhas, L. Zhao, R. N. Fariss, W. T. Wong; Age-Dependent Differences in the Dynamic Behavior of Retinal Microglia. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5759.
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© ARVO (1962-2015); The Authors (2016-present)
Resting retinal microglia demonstrate rapid and constant movements in their processes that are responsive to extracellular signals and to injury, and are likely important for immune function. Since age-related microglial senescence may contribute to neurodegenerative diseases such as age-related macular degeneration (AMD), we examined the effect of aging on the dynamic behavior of retinal microglia under both resting conditions and in response to stimuli.
Time-lapse confocal microscopy was used to monitor the behavior of green fluorescent protein (GFP)-labeled microglia in retinal explants from transgenic CX3CR1+/GFP mice. Microglia from young (1-2 months old) and aged (18-19 months old) mice were imaged under resting conditions and following the application of 1) focal laser injury, and 2) bath application of ATP (1mM). Images were processed and statistically analyzed using ImageJ and GraphPad Prism.
Under resting conditions, retinal microglial processes display marked dynamism, with those in the inner plexiform layer (IPL) demonstrating greater motility than those in the outer plexiform layer (OPL) (p < 0.005). Across age groups, mean process motility of microglia in the IPL was slightly, but non-significantly, lower in aged (2.9 ± 1.5 µm2/sec) versus young (3.1 ± 1.7 µm2/sec) mice. Mean process motility of microglia in the OPL was significantly lower in aged (1.8 ± 1.8 µm2/sec) versus young (2.1 ± 1.2 µm2/sec) mice (p < 0.05). In response to focal laser injury, microglia in both age groups increased the motility of their processes. Aged microglia, however, exhibited a significantly smaller mean increase (to 3.2 ± 1.3 µm2/sec) compared to young microglia (to 4.6 ± 3.1 µm2/sec). Microglial responses to exogenous ATP were also age-dependent. Young microglia significantly increased their baseline process motility (+37.9%; p < 0.0001) while aged microglia showed a converse decrease (-2.4%; p < 0.005). Similarly, in response to ATP, dendritic field area was significantly expanded in young microglia (+19.4%, p < 0.0001) but significantly decreased in aged microglia (-6.8%, p < 0.05).
Dynamic resting behavior and responses of retinal microglia demonstrate age-dependent differences. The ability of microglia to survey neural tissue and to respond to external signals likely declines with age, reflecting a functional senescence possibly important to the pathogenesis of age-related neuroinflammatory degenerations such as AMD.
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