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The aging phenotype of microglia in the retina and its relationship to AMD
Author(s) -
WONG W
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.1752.x
Subject(s) - microglia , retina , lipofuscin , retinal , neuroscience , inflammation , biology , pathogenesis , retinal degeneration , neurodegeneration , microbiology and biotechnology , medicine , immunology , pathology , biochemistry , disease
The association between age‐related retinal diseases and chronic inflammatory change in the retina raises the hypothesis that microglia, the resident immune cell in the retina, may undergo aging related changes that drive pathological change. In live imaging experiments, we discovered that “resting” microglia in the inner retina undergo aging changes in the forms of decreased ramification and slowed dynamic behavior. Also, dynamic responses to injury in aged microglia were slowed in the acute phase, but more prolonged in the chronic phase. These changes indicated that aged microglia may be less able to carry constitutive functions and have abnormal and more chronic responses to injury. Also, the age‐associated translocation of microglia into the subretinal space has been associated with intracellular lipofuscin accumulation. We found that microglial uptake of A2E, a key bisretinoid component of lipofuscin, increases activation, decreases chemotaxis, and dysregulates complement activation. Taken together, aging‐related changes in retinal microglia may result in increased neuronal vulnerability, dysregulated injury responses, and altered complement regulation in the outer retina that together contribute to AMD pathogenesis.