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Xue Cai, Sudipta Seal, James F McGinnis; Nanoceria protect the function of the RPE and the BRB in vldlr-/- mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The very low density lipoprotein receptor knockout (vldlr-/-) mouse is a model for “wet” Age-related Macular Degeneration (AMD). It exhibits neovascularization, dysfunction of the retinal pigment epithelium (RPE), breakdown of the blood-retinal barrier (BRB) and increased vascular permeability. In this study, we examine the effects of cerium oxide nanoparticles (nanoceria) on protection of the RPE health and the BRB function.
Albino vldlr-/- mice at P28 were intravitreally injected with 1µl of nanoceria (ranging from 0.001mM, 0.01mM, 0.1mM, 1mM to 10mM). Assessment was performed at P35 days and P7 months. Balb/C wild type (wt), untreated and saline injected vldlr-/- litter mates served as controls. Retinal neovascular “blebs” (RNV) and choroidal neovascular “tufts” (CNV) were counted using a vascular filling assay. Expression of RPE65 and junctional proteins was analyzed by flat mount immunofluorescence staining and western blots. Expression of vascular endothelial growth factor (VEGF), IL-6 and TNFα was determined by western blots. Vascular permeability was assessed by fluorescein angiography at a series of time points.
Nanoceria down regulated VEGF level and regressed RNV and CNV on a dose-dependent manner with 1mM producing the maximum effects. vldlr-/- mice have damaged RPE cells and BRB structure, and severe vascular leakage. Levels of RPE65, ZO-1, Cadherin, and Occludin in vldlr-/- mice were decreased and VEGF, IL-6 and TNFα were increased compared to wt. Nanoceria treatment reversed these effects and inhibited vascular leakage.
Nanoceria are effective in protecting RPE integrity, BRB loss and preventing increased vascular permeability by suppressing the expression of pro-inflammatory factors. Nanoceria may be an effective treatment strategy for AMD and other vascular diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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