School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China.
School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China.
Exp Eye Res. 2021 Jan;202:108332. doi: 10.1016/j.exer.2020.108332. Epub 2020 Nov 2.
Form deprivation myopia (FDM) is characterized by loss of choroidal thickness (ChT), reduced choroidal blood perfusion (ChBP), and consequently scleral hypoxia. In some tissues, changes in levels of peroxisome proliferator-activated receptor γ (PPARγ) expression modulate hypoxia-induced pathological responses. We determined if PPARγ modulates FDM through changes in ChT, ChBP, scleral hypoxia-inducible transcription factor (HIF-1α) that in turn regulate scleral collagen type 1 (COL1) expression levels in guinea pigs. Myopia was induced by occluding one eye, while the fellow eye served as control. They received daily peribulbar injections of either the PPARγ antagonist GW9662, or the GW1929 agonist, with or without ocular occlusion for 4 weeks. Ocular refraction and biometric parameters were estimated at baseline, 2 and 4 weeks post-treatment. ChT and ChBP were measured at the 2- and 4-week time points. Western blot analysis determined the expression levels of scleral HIF-1α and COL1. GW9662 induced a myopic shift in unoccluded eyes. Conversely, GW1929 inhibited FDM progression without affecting the refraction in unoccluded eyes. GW9662 reduced both ChT and ChBP in unoccluded eyes, while GW1929 inhibited their declines in occluded eyes. Scleral HIF-1α expression rose in GW9662-treated unoccluded eyes whereas GW1929 reduced HIF-1α upregulation in occluded eyes. GW9662 downregulated scleral COL1 expression in unoccluded eyes, while GW1929 reduced their decreases in occluded eyes. Therefore, PPARγ modulates collagen expression levels and FDM through an inverse relationship between changes in PPARγ and HIF-1α expression levels.
形觉剥夺性近视（FDM）的特征是脉络膜厚度（ChT）丧失、脉络膜血液灌注（ChBP）减少，进而导致巩膜缺氧。在一些组织中，过氧化物酶体增殖物激活受体 γ（PPARγ）表达水平的变化调节缺氧诱导的病理反应。我们确定 PPARγ 是否通过 ChT、ChBP、巩膜缺氧诱导转录因子（HIF-1α）的变化来调节 FDM，进而调节豚鼠巩膜胶原 1（COL1）的表达水平。通过阻塞一只眼睛来诱导近视，而对侧眼作为对照。它们每天接受球周注射 PPARγ 拮抗剂 GW9662 或 GW1929 激动剂，同时或不进行眼部阻塞，持续 4 周。在基线、治疗后 2 周和 4 周评估眼屈光和生物测量参数。在 2 周和 4 周时间点测量 ChT 和 ChBP。Western blot 分析确定了巩膜 HIF-1α 和 COL1 的表达水平。GW9662 诱导未阻塞眼出现近视漂移。相反，GW1929 抑制 FDM 进展，而不影响未阻塞眼的屈光。GW9662 降低了未阻塞眼的 ChT 和 ChBP，而 GW1929 抑制了阻塞眼的下降。GW9662 增加了 GW9662 处理的未阻塞眼中的 HIF-1α 表达，而 GW1929 降低了阻塞眼中的 HIF-1α 上调。GW9662 下调了未阻塞眼的巩膜 COL1 表达，而 GW1929 降低了阻塞眼的降低。因此，PPARγ 通过 PPARγ 和 HIF-1α 表达水平变化之间的反比关系调节 COL1 表达水平和 FDM。
