The traditionally protective cystathionine gamma-lyase/hydrogen sulfide pathway contributes to pathological retinal neovascularization in oxygen-induced retinopathy
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CSE is a key enzyme involved in the production of H2S and glutathione. CSE has been shown to protect against oxidative stress, attenuate ischemia/reperfusion injury, and promote angiogenesis, functions which are typically beneficial in ischemic tissue. However, retinal ischemia can cause pathological vessel growth which disrupts the precise ocular architecture and leads to irreversible vision loss. Our goal was to determine the role of the CSE/H2S pathway in ischemia-induced pathological retinal neovascularization (NV). C57BL/6 CSE -/- and +/- littermates were exposed to 75% oxygen from postnatal day (P)7 to P12 causing vaso-obliteration (VO). Mice were returned to room air, creating relative hypoxia and spurring retinal NV until sacrificed on P17. The retinal vasculature was stained and the retinas flat mounted for fluorescence microscopy. Areas of NV and VO were quantified using standardized methods. Pups were genotyped. Western blotting was used to measure protein levels. OIR markedly upregulated CSE in wild type mice compared to age matched controls in room air. CSE+/- mice exposed to OIR showed significantly less vaso-obliteration and significantly more neovascularization compared to CSE-/- littermates (p<0.05). Upregulation of CSE to enhance ischemic tolerance likely exacerbates pathological retinal neovascularization, the more clinically significant event. The CSE/H2S pathway appears to be involved in the pathogenesis of ischemia-induced neovascular disease.