Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan.
Department of Organic Synthesis, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan.
Curr Eye Res. 2019 Dec;44(12):1360-1368. doi: 10.1080/02713683.2019.1641825. Epub 2019 Jul 18.
: Retinopathy of prematurity (ROP) is characterized by morphological abnormalities in retinal blood vessels, but how an episode of ROP affects vascular function remains to be fully elucidated. The purpose of the present study was to assess the distribution of pericyte/smooth muscle in retinal blood vessels and retinal vasodilator responses in a rat model of ROP.: ROP was induced in rats by the subcutaneous injection of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8. The distribution of pericyte/smooth muscle in retinal blood vessels was examined on P14 and P35 by immunohistochemistry. Retinal vasodilator responses were assessed on P35 by measuring the diameter of retinal arterioles in fundus images.: In retinas of KRN633-treated (ROP) rats, progressive angiogenesis, tortuous arteries, enlarged veins, and enhanced expression of α-smooth muscle actin in pericytes on capillaries and veins were observed on P14. These abnormalities in retinal vasculature showed a tendency to normalize by P35. Vasodilation of retinal arterioles induced by acetylcholine, an endothelium-dependent vasodilator, was smaller in P35 ROP rats than age-matched controls, whereas retinal vasodilator responses to the nitric oxide (NO) donor NOR3 were unaltered.: Phenotypic changes in pericytes occur in the ROP model rats and endothelium-dependent vasodilatory mechanisms in retinal blood vessels are impaired. The impaired vasodilator function may contribute to the progression and pathogenesis of ROP.
早产儿视网膜病变（ROP）的特征是视网膜血管的形态异常，但ROP 发作如何影响血管功能仍有待充分阐明。本研究的目的是评估血管周细胞/平滑肌在ROP 大鼠模型中视网膜血管的分布和视网膜血管舒张反应。ROP 通过在出生后第 7 天和第 8 天（P）皮下注射血管内皮生长因子（VEGF）受体酪氨酸激酶抑制剂 KRN633（10mg/kg）诱导大鼠。通过免疫组织化学在 P14 和 P35 检查视网膜血管中周细胞/平滑肌的分布。通过测量眼底图像中视网膜小动脉的直径在 P35 评估视网膜血管舒张反应。在 KRN633 处理的（ROP）大鼠视网膜中，在 P14 观察到进行性血管生成、动脉扭曲、静脉扩大以及毛细血管和静脉中周细胞的α-平滑肌肌动蛋白表达增强。到 P35 时，视网膜血管的这些异常表现出趋于正常的趋势。与年龄匹配的对照组相比，乙酰胆碱诱导的视网膜小动脉舒张在 P35 ROP 大鼠中较小，而一氧化氮（NO）供体 NOR3 引起的视网膜血管舒张反应不受影响。周细胞的表型变化发生在 ROP 模型大鼠中，视网膜血管中的内皮依赖性血管舒张机制受损。受损的血管舒张功能可能导致 ROP 的进展和发病机制。
