Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.
Transl Vis Sci Technol. 2022 Oct 3;11(10):12. doi: 10.1167/tvst.11.10.12.
To evaluate the efficacy of a pigment epithelium-derived factor (PEDF)-derived short peptide 29-mer, on the treatment and prevention of experimental dry eye (EDE).
C57BL/6 mice were housed in a low humidity controlled environment chamber for 14 days to induce EDE. The 29-mer was administered topically to their eyes, for treatment or dosing, from the point of housing in the controlled environment chamber. The efficacy of the 29-mer on EDE was evaluated in terms of corneal epithelial integrity, tear secretion, and the density of conjunctival goblet cells. PEDF and inflammatory factors, including tumor necrosis factor-α, IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, matrix metalloproteinase-9, and macrophage infiltration, were examined by real-time polymerase chain reaction, Western blotting, and immunostaining. The involvement of the PEDF receptor/PNPLA2 on the 29-mer effects was evaluated by a specific inhibitor, atglistatin. Rabbit corneal epithelial cells were exposed to hyperosmotic medium to induce inflammatory responses.
The levels of PEDF protein increased in the corneal epithelium of EDE, compared with the nonstressed mice. The 29-mer showed a therapeutic effect on EDE and prevented the development of EDE, accompanied by amelioration of the inflammatory factors. The 29-mer effects of inflammatory relief were dramatically reversed by atglistatin. The 29-mer also suppressed the expression of matrix metalloproteinase-9 and proinflammatory cytokines in rabbit corneal epithelial cells induced by hyperosmolarity.
Through this animal study, we provide a proof of concept of the anti-inflammatory domain of PEDF having potential to treat dry eye disease.
This study shows the 29-mer has novel potential as an ophthalmic drop treatment for dry eye disease.
评估色素上皮衍生因子（PEDF）衍生的短肽 29 肽在治疗和预防实验性干眼症（EDE）中的疗效。
将 C57BL/6 小鼠饲养在低湿度控制环境室中 14 天，以诱导 EDE。从饲养在控制环境室的那一刻起，将 29 肽局部施用于它们的眼睛进行治疗或给药。通过评估角膜上皮完整性、泪液分泌和结膜杯状细胞密度来评估 29 肽对 EDE 的疗效。通过实时聚合酶链反应、Western blot 和免疫染色检查 PEDF 和炎症因子，包括肿瘤坏死因子-α、IL-1β、IL-6、单核细胞趋化蛋白（MCP）-1、基质金属蛋白酶-9 和巨噬细胞浸润。通过特异性抑制剂 atglistatin 评估 PEDF 受体/PNPLA2 对 29 肽作用的参与。将兔角膜上皮细胞暴露于高渗培养基中以诱导炎症反应。
与非应激小鼠相比，EDE 角膜上皮中 PEDF 蛋白水平升高。29 肽对 EDE 具有治疗作用，并可预防 EDE 的发生，同时改善炎症因子。atglistatin 显著逆转了 29 肽的抗炎作用。29 肽还抑制了高渗诱导的兔角膜上皮细胞中基质金属蛋白酶-9 和促炎细胞因子的表达。
通过这项动物研究，我们提供了 PEDF 的抗炎结构域具有治疗干眼症的潜力的概念验证。
王老师
