Maintaining retinal astrocytes normalizes revascularization and prevents vascular pathology associated with oxygen-induced retinopathy.
Maintaining retinal astrocytes normalizes revascularization and prevents vascular pathology associated with oxygen-induced retinopathy.
复制标题
DOI：
10.1002/glia.20900
复制
发表时间：
2010-01-01
期刊：
影响因子：
6.2
通讯作者：
Friedlander, Martin
中科院分区：
文献类型：
--
作者：
Dorrell, Michael I.;Aguilar, Edith;Jacobson, Ruth;Trauger, Sunia A.;Friedlander, Jeffrey;Siuzdak, Gary;Friedlander, Martin
星形胶质细胞是众所周知的正常发育视网膜血管化的调节剂。然而，人们对神经胶质细胞在病理性视网膜新生血管形成（NV）过程中的作用知之甚少，而病理性视网膜新生血管形成是工业化国家视力丧失的主要原因。我们证明，在氧诱导性视网膜病变 (OIR) 小鼠模型中，星形胶质细胞和小胶质细胞的丧失与病理性 NV 的发展直接相关。人们发现这两种不同的神经胶质细胞群在体外和体内具有协同生存效应。玻璃体内注射骨髓祖细胞、星形胶质细胞或星形胶质细胞条件培养基可挽救内源性星形胶质细胞免于变性，这种变性通常发生在缺氧、血管闭塞的视网膜内，恢复正常氧后。视网膜星形胶质细胞和小胶质细胞的保护与正常视网膜丛的加速血运重建以及通常与 OIR 相关的病理性玻璃体内 NV 的减少直接相关。使用星形胶质细胞条件培养基，确定了可能有助于观察到的星形胶质细胞保护和随后视网膜脉管系统正常化的几个因素，包括 VEGF 和 bFGF。注射特定剂量的 VEGF 或 bFGF 可以挽救视网膜，使其免于发生 OIR 相关病理，这种效果也可以保护内源性神经胶质细胞免受缺氧引起的退化。总之，这些数据表明血管相关神经胶质细胞也是缺氧视网膜正常血运重建所必需的。为靶向和保护神经胶质细胞而开发的方法可能提供一种新的策略，通过该策略可以促进正常的血运重建，并可以预防视网膜血管疾病中异常 NV 的后果。
Astrocytes are well known modulators of normal developmental retinal vascularization. However, relatively little is known about the role of glial cells during pathological retinal neovascularization (NV), a leading contributor to vision loss in industrialized nations. We demonstrate that the loss of astrocytes and microglia directly correlates with the development of pathological NV in a mouse model of oxygen induced retinopathy (OIR). These two distinct glial cell populations were found to have cooperative survival effects in vitro and in vivo. The intravitreal injection of myeloid progenitor cells, astrocytes, or astrocyte-conditioned media rescued endogenous astrocytes from degeneration that normally occurs within the hypoxic, vaso-obliterated retina following return to normoxia. Protection of the retinal astrocytes and microglia was directly correlated with accelerated revascularization of the normal retinal plexuses and reduction of pathological intravitreal NV normally associated with OIR. Using astrocyte-conditioned media, several factors were identified which may contribute to the observed astrocytic protection and subsequent normalization of the retinal vasculature, including VEGF and bFGF. Injection of VEGF or bFGF at specific doses rescued the retinas from developing OIR-associated pathology, an effect which was also preceded by protection of endogenous glia from hypoxia-induced degeneration. Together, these data suggest that vascular-associated glia are also required for normalized revascularization of the hypoxic retina. Methods developed to target and protect glial cells may provide a novel strategy by which normalized revascularization can be promoted and the consequences of abnormal NV in retinal vascular diseases can be prevented.
登录
查看更多内容
影响因子：
9.8
作者：
Adamis, A P;Aiello, L P;D'Amato, R A
通讯作者：
D'Amato, R A
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
影响因子：
13.7
作者：
Avery, RL;Pieramici, DJ;Giust, MJ
通讯作者：
Giust, MJ
VEGF164介导的炎症是病理学所必需的，但不是生理，缺血诱导的视网膜新血管形成。
影响因子：
15.3
作者：
Ishida, S;Usui, T;Yamashiro, K;Kaji, Y;Amano, S;Ogura, Y;Hida, T;Oguchi, Y;Ambati, J;Miller, JW;Gragoudas, ES;Ng, YS;D'Amore, PA;Shima, DT;Adamis, AP
通讯作者：
Adamis, AP
影响因子：
15.9
作者：
Dorrell, Michael I.;Aguilar, Edith;Friedlander, Martin
通讯作者：
Friedlander, Martin