Tsao Yu-Chien, Chen Shun-Hua, Ou Yi-Chun, Chuang Woei-Jer, Yang Chang-Hao, Lin Chia-Jhen, Hsu Sheng-Min
Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
FASEB J. 2025 Jul 31;39(14):e70844. doi: 10.1096/fj.202402498RR.
Proliferative vitreoretinopathy (PVR) is a severe complication after rhegmatogenous retinal detachment (RD) surgery and needs further surgical treatments. So far there are no effective drugs for prevention and treatment of PVR. Both integrins αvβ3 and α5β1 are related to human PVR formation. Disintegrins are antagonists of integrins. The drug, a mutant of snake venom-derived disintegrin, also called disintegrin Rhodostomin (Rho) mutant, is a potent antagonist of both integrins αvβ3 and α5β1, of which the effect on PVR remains poorly understood. In vitro assays were used to assess the effects of disintegrin Rho mutant treatment on the proliferation, migration, and adhesion of the retinal pigment epithelial (RPE) cell line derived from human, ARPE-19. In vivo, mice with PVR induction were treated with disintegrin Rho mutant and monitored for PVR severity. In vitro results showed that disintegrin Rho mutant reduced the migration, proliferation, and adhesion of ARPE-19 cells. In vivo results revealed that it could significantly ameliorate the severity of PVR and suppress expression of both integrin αvβ3 and α5β1 and epithelial-mesenchymal transition (EMT) in mouse eyes. Besides, we found decreases in Akt, STAT3, and ERK activation by disintegrin Rho mutant both in vitro and in vivo. In conclusion, disintegrin Rho mutant mitigates experimental PVR with reduced expression of both integrin αvβ3 and α5β1 and presents a potential therapeutic option for PVR in humans.
增殖性玻璃体视网膜病变（PVR）是孔源性视网膜脱离（RD）手术后的一种严重并发症，需要进一步的手术治疗。到目前为止，尚无有效的药物用于预防和治疗PVR。整合素αvβ3和α5β1均与人类PVR的形成有关。去整合素是整合素的拮抗剂。该药物是一种蛇毒衍生去整合素的突变体，也称为去整合素罗豆素（Rho）突变体，是整合素αvβ3和α5β1的强效拮抗剂，其对PVR的影响仍知之甚少。采用体外试验评估去整合素Rho突变体处理对源自人类的视网膜色素上皮（RPE）细胞系ARPE-19的增殖、迁移和黏附的影响。在体内，对诱导产生PVR的小鼠用去整合素Rho突变体进行处理，并监测PVR的严重程度。体外结果显示，去整合素Rho突变体降低了ARPE-19细胞的迁移、增殖和黏附。体内结果表明，它可显著改善PVR的严重程度，并抑制小鼠眼中整合素αvβ3和α5β1的表达以及上皮-间质转化（EMT）。此外，我们发现去整合素Rho突变体在体外和体内均可降低Akt、STAT3和ERK的激活。总之，去整合素Rho突变体可减轻实验性PVR，同时降低整合素αvβ3和α5β1的表达，为人类PVR提供了一种潜在的治疗选择。
