Intravitreal administration of recombinant human opticin protects against hyperoxia-induced pre-retinal neovascularization.
Intravitreal administration of recombinant human opticin protects against hyperoxia-induced pre-retinal neovascularization.
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DOI：
10.1016/j.exer.2021.108908
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发表时间：
2022-03
影响因子：
3.4
通讯作者：
Bainbridge JW
中科院分区：
文献类型：
--
作者：
Klaska IP;White A;Villacampa P;Hoke J;Abelleira-Hervas L;Maswood RN;Ali RR;Bunce C;Unwin RD;Cooper GJS;Bishop PN;Bainbridge JW
Opticin 是存在于玻璃体中的一种细胞外糖蛋白。其抗血管生成特性为增殖性糖尿病视网膜病变和早产儿视网膜病变等疾病的治疗干预提供了潜力。在这里，我们研究了这样的假设：玻璃体内施用重组人视蛋白可以安全地防止病理性血管生成的发展并促进其消退。我们生成并纯化了重组人视蛋白，并研究了其对小鼠氧诱导视网膜病玻璃体内给药后病理性视网膜新生血管形成的发展和消退的影响。我们还通过组织学检查和视网膜电图研究了新生小鼠玻璃体内注射后其对正常视网膜血管发育和功能的影响。在氧诱导性视网膜病变中，玻璃体内注射人重组视蛋白可防止视网膜新生血管形成，其程度与靶向 VEGF 的阿柏西普相似。 Opticin 还加速了已形成的视网膜新生血管的消退，但 18 小时时的效果低于阿柏西普。在新生小鼠中玻璃体内注射人重组视蛋白不会对随后的视网膜血管发育或功能造成可检测到的干扰。总之，我们发现眼内给予重组人视蛋白可防止小鼠病理性血管生成的发展并促进其消退。人重组视蛋白可防止小鼠病理性血管生成的发展。人重组视蛋白可加速小鼠视网膜前新生血管的消退。重组人视蛋白的眼内给药为新生血管性视网膜疾病提供了安全有效的治疗潜力。
Opticin is an extracellular glycoprotein present in the vitreous. Its antiangiogenic properties offer the potential for therapeutic intervention in conditions such as proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the hypothesis that intravitreal administration of recombinant human opticin can safely protect against the development of pathological angiogenesis and promote its regression. We generated and purified recombinant human opticin and investigated its impact on the development and regression of pathological retinal neovascularization following intravitreal administration in murine oxygen-induced retinopathy. We also investigated its effect on normal retinal vascular development and function, following intravitreal injection in neonatal mice, by histological examination and electroretinography. In oxygen-induced retinopathy, intravitreal administration of human recombinant opticin protected against the development of retinal neovascularization to similar extent as aflibercept, which targets VEGF. Opticin also accelerated regression of established retinal neovascularization, though the effect at 18 h was less than that of aflibercept. Intravitreal administration of human recombinant opticin in neonatal mice caused no detectable perturbation of subsequent retinal vascular development or function. In summary we found that intraocular administration of recombinant human opticin protects against the development of pathological angiogenesis in mice and promotes its regression. Human recombinant opticin protects against the development of pathological angiogenesis in mice. Human recombinant opticin accelerates regression of established pre-retinal neovascularization in mice. Intraocular administration of recombinant human opticin offers the potential for a safe and effective therapy for neovascular retinal diseases.
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影响因子：
4.9
作者：
del Amo, Eva M.;Griffiths, John R.;Unwin, Richard D.
通讯作者：
Unwin, Richard D.
影响因子：
4.4
作者：
Le Goff, Magali M.;Lu, Hongbin;Bishop, Paul N.
通讯作者：
Bishop, Paul N.
Opticin 通过调节细胞外基质粘附性发挥其抗血管生成活性。
DOI：
10.1074/jbc.m111.331157
发表时间：
2012-08-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Le Goff MM;Sutton MJ;Slevin M;Latif A;Humphries MJ;Bishop PN
通讯作者：
Bishop PN
DOI：
10.1056/nejmra1208129
发表时间：
2012-12-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hartnett ME;Penn JS
通讯作者：
Penn JS
影响因子：
3.9
作者：
Bishop, PN;Takanosu, M;Mayne, R
通讯作者：
Mayne, R