Plastic roles of pericytes in the blood-retinal barrier.
Plastic roles of pericytes in the blood-retinal barrier.
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DOI：
10.1038/ncomms15296
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发表时间：
2017-05-16
影响因子：
16.6
通讯作者：
Koh GY
中科院分区：
文献类型：
--
作者：
Park DY;Lee J;Kim J;Kim K;Hong S;Han S;Kubota Y;Augustin HG;Ding L;Kim JW;Kim H;He Y;Adams RH;Koh GY
血视网膜屏障（BRB）由紧密互连的毛细血管内皮细胞组成，周围覆盖有周细胞和神经胶质细胞，但周细胞在 BRB 调节中的作用尚不完全清楚。在这里，我们发现血小板源性生长因子（PDGF）-B/PDGF受体β（PDGFRβ）信号传导通过主动招募周细胞到生长的视网膜血管上，对于BRB的形成和成熟至关重要。由于 BRB 破坏，血管周细胞募集受损显示出糖尿病视网膜病变 (DR) 的多种血管特征。然而，PDGF-B/PDGFRβ 信号传导对于维持成年小鼠的 BRB 完整性来说是可牺牲的。尽管稳定成人视网膜血管中的选择性周细胞丢失令人惊讶地不会导致BRB崩解，但它使视网膜血管内皮细胞（EC）对VEGF-A敏感，通过FOXO1激活导致EC中血管生成素-2（Ang2）上调，并引发类似于DR发病机制的正反馈。因此，阻断 Ang2 或激活 Tie2 都会极大地减弱 BRB 分解，这表明了减少 DR 进展时视网膜损伤的潜在治疗方法。血视网膜屏障（BRB）由紧密连接的内皮和支持周细胞和神经胶质细胞组成。在此，作者表明，周细胞对于视网膜发育过程中 BRB 的形成及其在成人视网膜中的维持至关重要，通过调节 Tie2/FOXO1/Ang2 轴来响应 VEGF-A 诱导的内皮敏化。
The blood–retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption. However, PDGF-B/PDGFRβ signalling is expendable for maintaining BRB integrity in adult mice. Although selective pericyte loss in stable adult retinal vessels surprisingly does not cause BRB disintegration, it sensitizes retinal vascular endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2 (Ang2) in ECs through FOXO1 activation and triggering a positive feedback that resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic approaches to reduce retinal damages upon DR progression. Blood-retinal barrier (BRB) is composed of tightly connected endothelium and supporting pericytes and glia. Here, the authors show that pericytes are crucial for BRB buildup during retinal development and its maintenance in adult retinas in response to VEGF-A-induced endothelial sensitization by regulating the Tie2/FOXO1/Ang2 axis.