Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA.
Hudson Community College, Jersey City, NJ, USA.
Nat Commun. 2024 Oct 9;15(1):8757. doi: 10.1038/s41467-024-52675-x.
Proliferative vitreoretinopathy is a vision-threatening response to penetrating ocular injury, for which there is no satisfactory treatment. In this disorder, retinal pigment epithelial cells, abandon their attachment to Bruch's membrane on the scleral side of the retina, transform into motile fibroblast-like cells, and migrate through the retinal wound to the vitreal surface of the retina, where they secrete membrane-forming proteins. Annexin A2 is a calcium-regulated protein that, in complex with S100A10, assembles plasmin-forming proteins at cell surfaces. Here, we show that, in proliferative vitreoretinopathy, recruitment of macrophages and directed migration of retinal pigment epithelial cells are annexin A2-dependent, and stimulated by macrophage inflammatory protein-1α/β. These factors induce translocation of annexin A2 to the cell surface, thus enabling retinal pigment epithelial cell migration following injury; our studies reveal further that treatment of mice with intraocular antibody to either annexin A2 or macrophage inflammatory protein dampens the development of proliferative vitreoretinopathy in mice.
增生性玻璃体视网膜病变是一种威胁视力的穿透性眼损伤反应，目前尚无满意的治疗方法。在这种疾病中，视网膜色素上皮细胞脱离其在视网膜巩膜侧的附着处的 Bruch 膜，转化为运动的成纤维细胞样细胞，并通过视网膜伤口迁移到视网膜玻璃体表面，在那里它们分泌形成膜的蛋白。膜联蛋白 A2 是一种钙调节蛋白，与 S100A10 结合，在细胞表面组装形成纤维蛋白溶酶的蛋白。在这里，我们表明，在增生性玻璃体视网膜病变中，巨噬细胞的募集和视网膜色素上皮细胞的定向迁移依赖于膜联蛋白 A2，并受巨噬细胞炎症蛋白-1α/β的刺激。这些因子诱导膜联蛋白 A2向细胞表面易位，从而使视网膜色素上皮细胞在损伤后迁移；我们的研究进一步表明，用针对膜联蛋白 A2 或巨噬细胞炎症蛋白的眼内抗体治疗小鼠可抑制小鼠增生性玻璃体视网膜病变的发展。
