As the peroxisome proliferator – activated receptor alpha (PPARα) agonist, fenofibrate has been widely used to be a good lipid-regulating drug in the clinical application. In this study, we investigated the mechanism by which keratocytes inhibit the corneal neovascularization (CNV) through PPARα - activation. To do this, the CNV model was established by alkali burn, followed by being divided into three groups including control, fenofibrate and vehicle group. The expression of VEGFr3, MMP13 and PPARα in corneas of normal mouse and alkali-burned mouse was determined via quantitative RT- PCR (qRT-PCR) and Western blot analysis (WB). The CNV area was observed under a slit lamp microscope. The location of PPARα expression in the corneas was determined via immunohistochemistry. In cultured primary keratocytes, the effect of fenofibrate on PPARα, VEGFr3 and MMP13 expression was determined by qRT-PCR and WB. Besides, PPARα knockout (PPARα−/−) mouse CNV and keratocytes model were established to further confirm the effect of PPARα on VEGFr3 and MMP13 expression. We found that PPARα was expressed in epithelium, stroma and endothelium of the normal cornea, however, with relatively low level in the corneal stroma. Meanwhile, its expression was decreased markedly in the cornea during the stage of CNV formation. After treatment of fenofibrate, PPARα expression was promoted and the expression of VEGFr3 and MMP13 was inhibited in both CNV mice model and primary keratocytes, and CNV areas were decreased in CNV mice model. However, the results in PPARα−/− CNV and keratocytes model were opposite. Our results suggest that keratocytes could promote the expression of VEGFr3 and MMP13, and CNV formation through PPARα downregulation.

作为过氧化物酶体增殖物-活化受体α（PPARα）激动剂，非诺贝特已被广泛用作临床应用中的良好脂质调节药物。在这项研究中，我们研究了角膜细胞通过PPARα激活抑制角膜新生血管（CNV）的机制。为此，通过碱烧伤建立CNV模型，然后将其分为对照组，非诺贝特和赋形剂三组。通过定量RT-PCR（qRT-PCR）和蛋白质印迹分析（WB）测定正常小鼠和碱烧伤小鼠的角膜中VEGFr3，MMP13和PPARα的表达。在裂隙灯显微镜下观察CNV区域。通过免疫组织化学确定PPARα在角膜中的表达位置。在培养的原代角膜细胞中，非诺贝特对PPARα的作用 通过qRT-PCR和WB测定VEGFr3和MMP13的表达。此外，建立了PPARα基因敲除（PPARα-/-）小鼠CNV和角膜细胞模型，以进一步证实PPARα对VEGFr3和MMP13表达的影响。我们发现PPARα在正常角膜的上皮，基质和内皮中表达，但是在角膜基质中的表达相对较低。同时，在CNV形成阶段，其在角膜中的表达显着降低。非诺贝特治疗后，在CNV小鼠模型和原代角膜细胞中均促进PPARα表达，抑制VEGFr3和MMP13的表达，并且CNV小鼠模型中CNV面积减少。但是，PPARα-/-CNV和角膜细胞模型的结果相反。我们的结果表明，角化细胞可以促进VEGFr3和MMP13的表达，