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M. Zheng, M. Field, H. Qian, S.S. Atherton; Neovascularization in Acute Retinal Necrosis? . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4623.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: In humans, some cases of acute retinal necrosis (ARN) are associated with retinal neovascularization. The BALB/c mouse model of ARN was used to investigate the role of neovessels in the pathogenesis of ARN. Methods: The right eyes of BALB/c mice were inoculated in one anterior chamber with HSV-1 (KOS, 2 × 104 pfu/eye) or with an equivalent volume of tissue culture medium. On different days post inoculation (p.i.), 5 contralateral eyes of experimental and control mice were enucleated and pooled, and total RNA was isolated using Trizol. cDNA was synthesized from the RNA. PCR for mVEGF, VEGF receptor Flt-1 and KDR was performed. Immunohistochemical single staining was used to detect pan-endothelial antigen and mouse vascular endothelial growth factor (mVEGF); double staining was performed to detect mVEGF and RPE65; mVEGF and F4/80; and mVEGF and Gr-1 (granulocytes). Results: Pan-endothelial antigen positive cells were detected during the acute phase of ARN (day 9 p.i.) and increased at beginning of the resolution phase of the disease (day 14 p.i.). mVEGF mRNA was upregulated in both eyes of HSV-1 injected mice compared with both eyes of mice injected with medium alone. In HSV-1 injected mice, VEGF receptor 1 KDR was upregulated in the contralateral eye compared with the ipsilateral eye at all the time points observed. Compared with KDR, Flt-1 (VEGF receptor 2) was upregulated significantly in the contralateral eye compared with ipsilateral eyes of virus infected mice. mVEGF positive cells were observed during the acute phase of ARN. The cellular sources of VEGF were F4/80 positive macrophages, Gr-1 positive granulocytes, and RPE65 positive retinal pigment epithelial cells. Conclusions: These results support the idea that angiogenesis is involved in the pathogenesis of HSV-1 induced ARN in BALB/c mice. Upregulation of mVEGF in several cell types (infiltrating and residential retinal pigment epithelial cells) and of its receptors in the contralateral eyes at acute phase might be responsible at least in part for neovascularization in this model.
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