The Vitreous Glycoprotein Opticin Inhibits Preretinal Neovascularization

The Vitreous Glycoprotein Opticin Inhibits Preretinal Neovascularization
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DOI:
10.1167/iovs.11-8514
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发表时间:
2012-01-01
影响因子:
4.4
通讯作者:
Bishop, Paul N.
Bishop, Paul N.
中科院分区:
医学2区
文献类型:
--
作者:
Le Goff, Magali M.;Lu, Hongbin;Bishop, Paul N.

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目的。 Opticin 是作者在眼睛玻璃体液中发现的一种细胞外基质糖蛋白。它由非色素性睫状上皮合成并分泌到玻璃体腔中,并且对于细胞外基质分子来说不同寻常的是,高水平的合成一直维持到成年。在这里,作者研究了这样的假设:视蛋白影响眼睛后段的血管发育以及正常无血管、成熟(次级)玻璃体的病理性血管生成。方法。通过免疫组织化学,Opticin 定位于小鼠眼中。建立了 opticin 敲除小鼠,并比较了敲除小鼠和野生型小鼠的血管发育。在氧诱导的视网膜病变模型(病理性血管生成模型)中比较野生型和视蛋白缺失小鼠,并且该模型还用于评估将重组视蛋白玻璃体内注射到野生型小鼠眼中的效果。 结果。 Opticin 与玻璃体、内界膜、晶状体囊、小梁网和虹膜的富含 II 型胶原的纤维网络共定位。对玻璃体和视网膜血管系统的分析表明,视蛋白对玻璃体血管退化或发育性视网膜血管化没有影响。然而,作者利用氧诱导的视网膜病变模型证明,与野生型小鼠相比,opticin 敲除小鼠产生明显更多的视网膜前新生血管,并且玻璃体内输送过量的 opticin 抑制了野生型小鼠中新血管的形成。结论。缺乏视蛋白不会影响血管发育,但视蛋白具有抗血管生成作用并抑制视网膜前新生血管形成。 (投资眼科可见科学。2012 年;53:228-234)DOI:10.1167/iovs.11-8514
PURPOSE. Opticin is an extracellular matrix glycoprotein that the authors discovered in the vitreous humor of the eye. It is synthesized by the nonpigmented ciliary epithelium and secreted into the vitreous cavity and, unusually for an extracellular matrix molecule, high-level synthesis is maintained into adult life. Here the authors investigated the hypothesis that opticin influences vascular development in the posterior segment of the eye and pathologic angiogenesis into the normally avascular, mature (secondary) vitreous.METHODS. Opticin was localized in murine eyes by immunohistochemistry. An opticin knockout mouse was established and vascular development was compared between knockout and wild-type mice. Wild-type and opticin null mice were compared in the oxygen-induced retinopathy model, a model of pathologic angiogenesis, and this model was also used to assess the effects of intravitreal injection of recombinant opticin into eyes of wild-type mice.RESULTS. Opticin colocalizes with the collagen type II-rich fibrillar network of the vitreous, the inner limiting lamina, the lens capsule, the trabecular meshwork, and the iris. Analyses of the hyaloid and retinal vasculature showed that opticin has no effect on hyaloid vascular regression or developmental retinal vascularization. However, using the oxygen-induced retinopathy model, the authors demonstrated that opticin knockout mice produce significantly more preretinal neovascularization than wild-type mice, and the intravitreal delivery of excess opticin inhibited the formation of neovessels in wild-type mice.CONCLUSIONS. A lack of opticin does not influence vascular development, but opticin is antiangiogenic and inhibits preretinal neovascularization. (Invest Ophthalmol Vis Sci. 2012;53:228-234) DOI:10.1167/iovs.11-8514