Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia 30912-2500, USA.
Invest Ophthalmol Vis Sci. 2011 Aug 11;52(9):6384-95. doi: 10.1167/iovs.11-7666.
To investigate the therapeutic use and mechanisms of action of normobaric hyperoxia to promote revascularization and to prevent neovascularization in a mouse model of oxygen-induced ischemic retinopathy.
Hyperoxia treatment (HT, 40%-75% oxygen) was initiated on postnatal day (P) 14 during the pre-proliferative phase of ischemic retinopathy. Immunohistochemistry, ELISA, and quantitative PCR were used to assess effects on retinal vascular repair and pathologic angiogenesis in relation to glial cell injury, VEGF protein, and mRNA levels of key mediators of pathologic angiogenesis. Effects of intravitreal injections of VEGF and the VEGF inhibitor VEGFR1/Fc fusion protein were also studied.
Administration of HT during the ischemic pre-proliferative phase of retinopathy effectively accelerated the process of revascularization while preventing the development of vitreous neovascularization. HT enhanced the formation of specialized endothelial tip cells at the edges of the repairing capillary networks and blocked the overexpression of several molecular mediators of angiogenesis, inflammation, and extracellular proteolysis. HT markedly reduced the reactive expression of GFAP in Müller cells and improved the morphology of astrocytes in the avascular region of the retina. Exogenous VEGF administered into the vitreous on P14 was not sufficient to cause vitreous neovascularization in the HT mice. Injection of the VEGF antagonist VEGFR1/Fc blocked both pathologic and physiological angiogenesis and did not rescue astrocytes.
HT may be clinically useful to facilitate vascular repair while blocking neovascularization in the pre-proliferative stage of ischemic retinopathy by correcting a broad range of biochemical and cellular abnormalities.
研究常压高氧治疗促进血管再生和预防氧诱导缺血性视网膜病变小鼠模型新生血管形成的治疗作用和作用机制。
在缺血性视网膜病变的前增殖期，于出生后第 14 天（P）开始进行高氧治疗（HT，40%-75%氧气）。免疫组织化学、ELISA 和定量 PCR 用于评估对视网膜血管修复和与神经胶质细胞损伤、VEGF 蛋白以及病理性血管生成关键介质的 mRNA 水平相关的病理性血管生成的影响。还研究了玻璃体内注射 VEGF 和 VEGF 抑制剂 VEGFR1/Fc 融合蛋白的效果。
在视网膜病变的缺血前增殖期给予 HT 可有效加速血管再生过程，同时防止玻璃体新生血管形成。HT 增强了修复毛细血管网络边缘处的专门内皮尖端细胞的形成，并阻断了几种血管生成、炎症和细胞外蛋白水解的分子介质的过度表达。HT 明显降低了 Müller 细胞中 GFAP 的反应性表达，并改善了无血管区视网膜中星形胶质细胞的形态。在 P14 时将外源性 VEGF 注入玻璃体不足以在 HT 小鼠中引起玻璃体新生血管形成。注射 VEGF 拮抗剂 VEGFR1/Fc 阻断了病理性和生理性血管生成，并且不能挽救星形胶质细胞。
HT 可能在缺血性视网膜病变的前增殖期通过纠正广泛的生化和细胞异常而具有临床应用价值，以促进血管修复并阻断新生血管形成。
