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W. Raoul, C. Combadiere, N. Keller, M. Rodero, J. C. Jeanny, F. Behar-Cohen, F. Sennlaub; Retinal Degeneration Occurs in Cx3cr1 Knockout Animals Secondary to Subretinal Microglia Accumulation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3023.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal microglial cells express CX3CR1 and subretinal microglial cells (SrMC) accumulate with age in CX3CR1 deficient animals (abstract ARVO 2007 Sennlaub). SrMC accumulation occurs in albino animals and light-induced models in WT animals. Here we studied the influence of CX3CR1 on SrMC populations on albino background and light-injury and their effect on retinal integrity using Balb CX3CR1-/- (albino) and C57Bl6 CX3CR1-/- (pigmented) animals
We used 1 to 5-months old Balb CX3CR1 WT and KO mice under normal light conditions or raised in total obscurity. We also studied C57Bl6 CX3CR1+/GFP and CX3CR1GFP/GFP mice after exposition to 10min of 500 Klux light up to 40d. Immunostaining for GFP, CD11b, F4/80, Phalloidine and 5D4 were performed on RPE/choroid flatmounts and transmission electron microscopy on eye sections. We evaluated SrMC population and RPE integrity as well as photoreceptor layer (PRL) thickness
A) Balb CX3CR1-/- showed a significantly more important and increasing SrMC population at 1 and 2 months of age compared to WT mice. At 4 months complete degeneration of photoreceptors and patchy RPE cell degeneration was observed in Balb CX3CR1-/-. Balb CX3CR1-/- mice raised in complete obscurity were protected against excessive SrMC accumulation and did not develop degeneration B) Similarly, illuminated CX3CR1GFP/GFP developed exacerbated sustained increase in SrMC population followed by disappearance of 50% of photoreceptors by d40. WT mice only developed a modest transient increase and no retinal degeneration under these light-injury conditions
Our data show that CX3CR1 deficiency leads to SrMC accumulation in light injury in pigmented mice and in a light dependent manner in albino animals. Surprisingly, the microglial accumulation leads to severe (C57Bl6) and complete (Balb) photoreceptor degeneration in the absence of primary RPE or photoreceptor disease. These findings show a completely novel mechanism in retinal degeneration, which might be an aggravating factor in Retinitis pigmentosa and AMD
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