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Xu Wang, Lian Zhao, Christopher Parkhurst, Wen-biao Gan, Robert N Fariss, Wai T Wong; Microglial Depletion in the Adult Mouse Retina: Effects on Retinal Cell Death and Inflammation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2264. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
In retinal pathologies, microglia have been implicated in regulating trophic influences to retinal neurons and gliosis in macroglia. However, whether microglia exert such regulatory functions in a constitutive manner in the healthy adult retina is unclear. We explore this question by examining the effects of sustained microglial depletion in the adult mouse retina.
Transgenic mice on a C57Bl6 background in which the Cx3cr1 gene was replaced by a sequence encoding a mutant Cre protein with a tamoxifen (TAM)-dependent estrogen ligand-binding domain (Cx3cr1CreER) were crossed with mice carrying lox-P-flanked (‘floxed’) diphtheria toxin (DTA) to create Cx3cr1CreER/+ DTA/+ (TG) mice. Depletion of retinal microglia in TG mice was induced by TAM gavage and was sustained over 30 days by repeated administration. Histological changes in the retina were monitored in retinal sections and flat-mounted preparations.
Following 30 days of sustained microglial depletion (<1% of microglia remaining), histological analyses revealed that overall retinal organization relative to untreated controls was maintained without detectable changes in retinal lamination or thicknesses in retinal cell layers. Apoptosis, as detected by TUNEL staining, was not induced in any retinal layer. The structure and laminar organization of retinal vasculature, which are normally in close proximity to microglia, remained unaffected. The morphologies of retinal astrocytes and Müller cells, as revealed by immunohistochemical labeling for GFAP and glutamine synthetase respectively, were similar to controls; signs of Müller cell gliosis, as evidenced by process hypertrophy or GFAP upregulation, were also absent.
Microglial absence in the mouse retina for intervals up to 1 month did not induce detectable neuronal cell death, vascular change, or alterations in macroglial morphology and activation. Retinal microglia do not appear necessary for retinal cell survival or for the maintenance of astrocyte and Müller cell morphology or physiology. Studies to discover any constitutive microglial contribution to retinal cell function and retinal synaptic structure are currently ongoing.
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