Functional Analyses of TNFR2 in Physiological and Pathological Retina Angiogenesis

Abstract

TNFR2 plays a marginal role during retinal vascular development. TNFR2 in vascular EC strongly prevents hyperoxia-induced vaso-obliteration by inhibiting cell apoptosis, and promotes retinal repair by enhancing hypoxia-induced revascularization without increasing pathological neovascular tufts. Therefore, activation of TNFR2 signaling may be an ideal strategy for the treatment of OIR.

TNF-α Genetic Predisposition and Higher Expression of Inflammatory Pathway Components in Keratoconus

“…Also, the higher levels of TNFR2 in the presence of increased concentrations of TNF-a can lead to activation of signaling pathways beyond the physiological levels, thus resulting in inflammation. The results were found consistent with the findings of Mohan et al, 35 Wan et al, 36 and Nakazawa et al, 37 who found upregulation of TNFR2 in the human corneal fibroblast, retinal ganglion cells in a mouse model of glaucoma, and retina of an oxidative-stress-induced retinopathy mouse model. In contrast to the current findings, Bryant-Hudson et al, 38 Shivanna et al, 39 and Tezel et al 40 have reported significantly lower expression levels of TNFR2 and higher expression levels of TNFR1 in mouse cornea infected with herpes simplex virus 1, cultured bovine corneal endothelial cells, and retina of normal and glaucomatous eyes.…”

Tumor Necrosis Factor Alpha and Interleukin-6 Facilitate Corneal Lymphangiogenesis in Response to Herpes Simplex Virus 1 Infection

“…To further characterize the role of TNF-␣ in corneal lymphangiogenesis, we investigated whether the effect was mediated through TNFR p55 (R1) or TNFR p75 (R2) pathways. Both TNFR1 and TNFR2 have been found to be involved in ocular neovascularization coupled with angiopoietin or fibroblast growth factor (22,23). However, the absence of either of these receptors had no significant detriment to corneal lymphangiogenesis in response to HSV-1 infection.…”

Gene expression in retinal ischemic post-conditioning

“…All of the genes present in Supp. Table 3 had significantly increased expression in PCI vs ShamN compared to ShamI vs Sham N. Some of these genes (e.g., Cflar, Gadd45b, Nfkbia, Birc3 and 5, and Nfkb1) are known anti-apoptosis, pro-survival genes, while others (e.g., Fos, Parp3, Fas, and Tnfrsf1a [28, 29]) are pro-apoptotic. Therefore, it is likely that survival or death from apoptosis is dependent upon a balance of these pro- and anti-apoptosis genes, and may also depend upon the timing of their expression, not specifically addressed in this study, where we only measured gene expression at one time point.…”