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Andrew Jobling, Kirstan Vessey, Michelle Waugh, Joanna Phipps, Erica Fletcher; The role of Cx3cr1 signalling in photoreceptor development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3724.
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The microglial receptor, Cx3CR1, has been implicated in age-related macular degeneration and also neuronal modulation in the brain. This study characterised the role retinal microglia play in modulating photoreceptor development and integrity in an animal model lacking Cx3cr1.
Cx3cr1null mice (Cx3cr1GFP/GFP) were studied at times ranging from P14 (eye opening) to 9 months of age. Retinal function was assessed using the electroretinogram and microglial - photoreceptor associations were investigated using immunohistochemistry. Whole retinal gene expression profile was detailed using a BeadChip array and specific genes were quantified using real-time PCR.
In the Cx3cr1null animals, gene array data showed a decrease in a number of genes associated with the photoreceptor cilium at P14, suggesting photoreceptor development was altered. Between P14 and 1 month of age there was an increase in opsin expression in the retinae of wild type mice, reflecting outer segment maturation, however in the Cx3cr1null, opsin expression remained at pre-eye opening levels. The Cx3cr1null retinae showed increased microglial cell bodies and processes in the outer nuclear layer (ONL) from eye opening onwards and there was extensive Müller cell gliosis. The Cx3cr1null animals showed decreased cone pathway function (-53%) and a 30% loss of cone numbers by 3 months of age. These cone-related deficits were maintained out to 9 months, by which time the rod pathway also exhibited a functional decrease (-22%).
These data suggest that very early changes in microglial-photoreceptoral interaction via Cx3cr1 signalling may result in abnormal photoreceptor maturation and cell death. These early developmental alterations may highlight a role for microglia in photoreceptor development and maintenance and may help explain the association of Cx3CR1 polymorphisms with age related macular degeneration.
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