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Paul G. McMenamin, Holly Chinnary, Nina Vagaja; Hyalocytes And Subretinal Macrophages: Are These Myeloid-derived Cells The ‘Canaries In The Mine’ At The Neural Retinal Interface?. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4760. doi: https://doi.org/.
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Resident cells of myeloid origin in the retina and adjacent tissues have a potential role in a range of diseases including uveitis, viral retinitis, diabetes and age-related macular degeneration (AMD). In light of the strategic location of hyalocytes and subretinal macrophages (SRMΦ) we have investigated changes in their numbers and phenotype in response to ageing, eye pigmentation, hyperglycaemia and systemic exposure to inflammatory stimuli.
The following mice were used in the present study: Cx3cr1gfp/gfp and Cx3cr1gfp/+mice both on BALB/c and C57Bl/6 backgrounds; WT controls;Ins2Akita mice. In addition we have investigated the effects of systemic exposure to TLR4 and TLR9 ligands (LPS and CpG-ODN) on hyalocytes and SRMΦ. Eyes were examined by SLO/OCT, fundus photography, fluorescein angiography and confocal microscopy of stained tissue wholemounts.
There was a marginal increase in the numbers of Iba-1+ F4/80+ CD169+ hyalocytes in older eyes (16-17 wks vs 6 wks). In older C57Bl/6 mice hyalocytes accumulated melanin. Hyalocyte density increased 2-3 weeks after onset of hyperglycaemia and 24hr following systemic LPS. Quantitative analysis of RPE-choroidal wholemounts revealed no differences in SRMΦ number in young Cx3cr1gfp/+ C57Bl/6 and BALB/c mice however albino Cx3cr1gfp/gfp mice had increased SRMΦ numbers compared to albino Cx3cr1gfp/+ mice. Large numbers of CD45+ F4/80+, Iba-1+ CD68+ SRMΦ/activated microglia were noted in both old pigmented Cx3cr1gfp/gfp and Cx3cr1gfp/+ mice. One week after exposure to the TLR9 ligand CpG-ODN, but not LPS, there was an increase in the density of SRMΦ.
This study demonstrates that these two populations of myeloid-derived cells differ in their response to the challenges brought about by aging, hyperglycaemia and exposure to systemic inflammatory stimuli. We propose that alterations to hyalocyte and SRMΦ phenotype and density may be early warning signs of para-inflammatory changes in the retina prior to overt morphological retinal degenerative changes. This may be significant as activated hyalocytes and SRMΦ may act as a source of chemokines and VEGF thus contributing to more severe retinal disease.
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