Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China.
Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China.
Lab Invest. 2022 Dec;102(12):1296-1303. doi: 10.1038/s41374-022-00822-7. Epub 2022 Jul 19.
Proliferative vitreoretinopathy (PVR) is a fibrotic eye disease that develops after rhegmatogenous retinal detachment surgery and open-globe traumatic injury. Idelalisib is a specific inhibitor of phosphoinositide 3-kinase (PI3K) δ. While PI3Kδ is primarily expressed in leukocytes, its expression is also considerably high in retinal pigment epithelial (RPE) cells, which play a crucial part in the PVR pathogenesis. Herein we show that GeoMx Digital Spatial Profiling uncovered strong expression of fibronectin in RPE cells within epiretinal membranes from patients with PVR, and that idelalisib (10 μM) inhibited Akt activation, fibronectin expression and collagen gel contraction induced by transforming growth factor (TGF)-β2 in human RPE cells. Furthermore, we discovered that idelalisib at a vitreal concentration of 10 μM, a non-toxic dose to the retina, prevented experimental PVR induced by intravitreally injected RPE cells in rabbits assessed by experienced ophthalmologists using an indirect ophthalmoscope plus a + 30 D fundus lens, electroretinography, optical coherence tomography and histological analysis. These data suggested idelalisib could be harnessed for preventing patients from PVR.
增殖性玻璃体视网膜病变（PVR）是一种纤维性眼病，发生于孔源性视网膜脱离手术后和眼穿通伤后。Idelalisib 是一种磷酸肌醇 3-激酶（PI3K）δ的特异性抑制剂。虽然 PI3Kδ主要在白细胞中表达，但在视网膜色素上皮（RPE）细胞中的表达也相当高，而 RPE 细胞在 PVR 发病机制中起着至关重要的作用。在这里，我们发现 GeoMx 数字空间分析揭示了 PVR 患者的视网膜前膜中 RPE 细胞中纤维连接蛋白的强烈表达，并且 idelalisib（10μM）抑制了 Akt 激活、纤维连接蛋白表达和转化生长因子（TGF）-β2诱导的人 RPE 细胞胶原凝胶收缩。此外，我们发现，idelalisib 在玻璃体浓度为 10μM 时，对视网膜无毒，可预防兔眼内注射 RPE 细胞诱导的实验性 PVR，经验丰富的眼科医生使用间接检眼镜加+30D 眼底镜、视网膜电图、光学相干断层扫描和组织学分析进行评估。这些数据表明，idelalisib 可用于预防患者发生 PVR。
