Iribarne María, Ogawa Liliana, Torbidoni Vanesa, Dodds Cristian M, Dodds Ricardo A, Suburo Angela M
Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires, Argentina.
Am J Pathol. 2008 Apr;172(4):1030-42. doi: 10.2353/ajpath.2008.070605. Epub 2008 Feb 29.
Proliferative vitreoretinopathy (PVR) is characterized by severe glial remodeling. Glial activation and proliferation that occur in brain diseases are modulated by endothelin-1 (ET-1) and its receptor B (ETR-B). Because retinal astrocytes contain ET-1 and express ETR-B, we studied the changes of these molecules in an experimental mouse model of PVR and in human PVR. Both ET-1 and ETR-B immunoreactivities increased in mouse retina after induction of PVR with dispase. Epi- and subretinal outgrowths also displayed these immunoreactivities in both human and experimental PVR. Additionally, myofibroblasts and other membranous cell types showed both ET-1 and ETR-B immunoreactivities. In early stages of experimentally induced PVR, prepro-ET-1 and ETR-B mRNA levels increased in the retina. These mRNA levels also increased after retinal detachment (RD) produced by subretinal injection. Treatment of mice with tezosentan, an antagonist of endothelinergic receptors, reduced the histopathological hallmarks of dispase-induced PVR: retinal folding, epiretinal outgrowth, and gliosis. Our findings in human and in dispase-induced PVR support the involvement of endothelinergic pathways in retinal glial activation and the phenotypic transformations that underlie the growth of membranes in this pathology. Elucidating these pathways further will help to develop pharmacological treatments to prevent PVR. In addition, the presence of ET-1 and ETR-B in human fibrous membranes suggests that similar treatments could be helpful after PVR has been established.
增殖性玻璃体视网膜病变（PVR）的特征是严重的神经胶质重塑。脑疾病中发生的神经胶质激活和增殖受内皮素-1（ET-1）及其受体B（ETR-B）调节。由于视网膜星形胶质细胞含有ET-1并表达ETR-B，我们研究了这些分子在PVR实验小鼠模型和人类PVR中的变化。用dispase诱导PVR后，小鼠视网膜中ET-1和ETR-B免疫反应性均增加。在人类和实验性PVR中，视网膜上和视网膜下的增生也显示出这些免疫反应性。此外，肌成纤维细胞和其他膜性细胞类型均显示出ET-1和ETR-B免疫反应性。在实验诱导的PVR早期，视网膜中前体ET-1和ETR-B mRNA水平升高。视网膜下注射导致视网膜脱离（RD）后，这些mRNA水平也升高。用内皮素能受体拮抗剂替唑生坦治疗小鼠，可减轻dispase诱导的PVR的组织病理学特征：视网膜折叠、视网膜前增生和胶质增生。我们在人类和dispase诱导的PVR中的发现支持内皮素能途径参与视网膜神经胶质激活以及该病理学中膜生长基础的表型转变。进一步阐明这些途径将有助于开发预防PVR的药物治疗方法。此外，人类纤维膜中存在ET-1和ETR-B表明，在PVR形成后进行类似治疗可能会有帮助。
