Jennifer L Wilkinson-Berka
Inflammation is a key contributor to thedevelopment of ischemic retinopathies such as retin-opathy of prematurity (ROP). However, the role of theadaptive immune system in ROP is largely unknown.This is despite its essential role in controlling theinflammatory response of the body, its emerging rolesin neovascularization, and reports that cytokines suchas interleukin (IL)-6, IL-8 and IL-17 are increased inchildren with ROP.
Studies were performed in a mouse modelof ROP, known as oxygen-induced retinopathy (OIR).Mice at post-natal day (P) 7 were exposed to 75%oxygen until P12 and then room air until P18. Controlswere in room air.
Results: In RAG-1 knockout mice, which are defi-cient in T cells and B cells, retinal capillary degenera-tion and neovascularization were reduced. In ROP, Tcells rather than B cells play a causal role, with CD3+Tcells increased in retina, and vasculopathy not attenu-ated in muMt mice that are deficient in B cells. Areduction in immunosuppressive FoxP3+Tregsmay contribute to ROP pathogenesis as CD4+CD25+FoxP3+Tregs although increased in lymphoid organsin acute retinal ischemia, are reduced when reti-nal neovascularization is established. The renin-angiotensin system may influence this process as theangiotensin type 1 receptor (AT1R) is expressed onFoxP3+Tregs and AT1R blockade reduces vasculopathyin ROP with a concomitant enhancement of FoxP3+Tregs in lymphoid organs and FoxP3 expression inertia.
Conclusion: The adaptive immune system may con-tribute to vasculopathy in ROP, which is influenced bythe renin-angiotensin system.