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Edith Aguilar, Toshihide Kurihara, Peter D. Westenskow, Stephen Bravo, Martin Friedlander; Myeloid Cells are Associated with Subretinal Neovascular Angiomas in a Murine Model of Macular Telangiectasia. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3022.
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The pathogenesis of macular telangiectasia (MacTel) is unclear and currently no approved treatment is available. We have previously characterized the retinal phenotypes from very low density lipoprotein receptor (VLDLR) mutant mice. We demonstrated that these mice exhibit very similar phenotypes to MacTel patients including subretinal neovascularization and photoreceptor degeneration (Dorrell J et al. J Clin Invest. 2009). However, the mechanisms initiating and directing normal blood vessels ectopically into the outer nuclear layer have not been identified. Since pronounced myeloid cell recruitment is commonly observed during angiogenesis, we hypothesized that myeloid cells may also be recruited to regions of VLDLR mutant eyes in which pathological angiogenesis is occurring.
Knock-in transgenic mice expressing GFP under the control of a CX3CR1 promoter (CX3CR1GFP/GFP), were crossed with VLDLR mutant mice. These crosses yielded pups with GFP positive myeloid cells in mice with MacTel-like phenoytpes (VLDLR-/-;CX3CR1GFP/+). Immunohistochemistry was performed on retinal flat mounts and on thick vibratome sectioned sensory retinas. Confocal microscopy was utilized to image the spatial orientation of GFP positive myeloid cells in relation to immunofluorescently labeled vascular networks.
Myeloid cells are observed in a much higher frequency in the subretinal space of VLDLR-/-;CX3CR1GFP/+ mice than in controls (CX3CR1GFP/+). Myeloid cells are also consistently observed in very close proximity to neovascular tufts in the deep plexus vascular layer and seem to wrap long processes around the angiomas as they are forming.
While highly correlative, the distribution of myeloid cells in close proximity to the angiomas of VLDLR mutant mice may provide evidence that myeloid cells provide support to or regulate pathological angiogenesis. The results of this study may have applications for the development of novel therapeutic strategies for treating MacTel phenotypes.
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