Development of an opticin-based anti-angiogenic therapeutic for the treatment of ocular disease.

开发基于光学蛋白的抗血管生成疗法，用于治疗眼部疾病。

• 批准号: MR/M025365/1
• 负责人: Paul Bishop
• 金额: $ 80.62万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM025365%2F1
• 关键词: Development; opticin; based; anti; angiogenic

There are a number of blinding conditions where abnormal blood vessels grow into the vitreous humour, a normally transparent, jelly-like structure that occupies the middle of the eye; these include retinopathy of prematurity (affecting preterm babies) and proliferative diabetic retinopathy (a common cause of sight loss in diabetes). Currently these conditions are treated with laser therapy that destroys large parts of the retina; this sacrifices side-vision with the aim of preventing complete sight loss and preserving the central part of the vision. Laser treatment was introduced about 50 years ago and the treatment for these conditions has not changed substantially since then. Given the side-effects of laser treatment, and that it does not always work, better treatments are need. We discovered a molecule in the vitreous humour that we called opticin, and more recently we found that opticin inhibits blood vessel growth. In diseases where blood vessels grow into the vitreous there is not enough opticin present to stop the blood vessels growing. However, we now have evidence that by injecting more opticin into the vitreous than is normally present, we can prevent the blood vessel growth and thereby treat these diseases. Injections into the vitreous are now routine procedures for other eye conditions and injecting opticin could replace laser treatment, or could be used in conjunction with laser therapy. This project will build upon the data we have at present to substantiate the case for developing opticin as a treatment for these conditions. Studies will include further work to determine how effective opticin will be as a treatment, some initial safety studies, investigations into how long the opticin stays in the vitreous humour after it is injected, and some further work to analyse how opticin works at a molecular level. This preclinical research will allow us to detemine whether opticin should continue to be developed as a treatment, and if it does, will facilitate future research as it moves towards clinical trials. In addition, it will provide the data needed to attract a commercial partner with whom we can develop opticin into an exciting, new sight-saving treatment.

有一些致盲的情况是，异常的血管生长到玻璃体中，玻璃体通常是透明的，果冻状的结构，占据眼睛的中间；这些包括早产儿视网膜病变（影响早产儿）和增殖性糖尿病视网膜病变（糖尿病患者视力丧失的常见原因）。目前，这些病症是用激光疗法治疗的，这种疗法会破坏视网膜的大部分；这种方法牺牲了侧视，目的是防止完全失明并保留视力的中心部分。激光治疗大约在50年前被引入，自那时以来，对这些疾病的治疗并没有实质性的改变。考虑到激光治疗的副作用，而且它并不总是有效，需要更好的治疗方法。我们在玻璃体幽默中发现了一种叫做视光素的分子，最近我们发现视光素可以抑制血管生长。在血管生长到玻璃体的疾病中，没有足够的视色素来阻止血管生长。然而，我们现在有证据表明，通过向玻璃体注入比正常情况下更多的视蛋白，我们可以防止血管生长，从而治疗这些疾病。玻璃体注射现在是治疗其他眼病的常规方法，注射视色素可以取代激光治疗，或者可以与激光治疗结合使用。这个项目将建立在我们目前拥有的数据基础上，以证实开发光学作为治疗这些疾病的方法。研究将包括进一步的工作，以确定视黄酮作为一种治疗方法的有效性，一些初步的安全性研究，调查注射后视黄酮在玻璃体中停留的时间，以及进一步分析视黄酮在分子水平上的作用。这项临床前研究将使我们能够确定是否应该继续开发opticin作为一种治疗方法，如果是的话，将促进未来的研究，因为它将走向临床试验。此外，它将提供吸引商业合作伙伴所需的数据，我们可以与他们一起将光学发展成一种令人兴奋的、新的视力保护治疗方法。

项目成果

Analysis of opticin binding to collagen fibrils identifies a single binding site in the gap region and a high specificity towards thin heterotypic fibrils containing collagens II, and XI or V/XI

光学蛋白与胶原原纤维结合的分析确定了间隙区域中的单个结合位点，并且对含有胶原蛋白 II、XI 或 V/XI 的细异型原纤维具有高度特异性

• DOI: 10.1101/2020.06.02.129403
• 发表时间: 2020
• 作者: Hansen U

Analysis of opticin binding to collagen fibrils identifies a single binding site in the gap region and a high specificity towards thin heterotypic fibrils containing collagens II, and XI or V/XI.

对与胶原原纤维结合的视蛋白的分析确定了间隙区域中的单个结合位点以及对含有胶原蛋白 II、XI 或 V/XI 的细异型原纤维的高特异性。

• DOI: 10.1371/journal.pone.0234672
• 发表时间: 2020
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hansen U

Intravitreal administration of recombinant human opticin protects against hyperoxia-induced pre-retinal neovascularization.

• DOI: 10.1016/j.exer.2021.108908
• 发表时间: 2022-03
• 期刊: Experimental eye research
• 影响因子: 3.4
• 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
• 通讯作者: Bainbridge JW

Extracellular matrix in retinal vascular development and pathological angiogenesis

细胞外基质在视网膜血管发育和病理性血管生成中的作用

• 发表时间: 2016
• 作者: Bishop PN

Human opticin reduces pathological preretinal neovascularization in the mouse model of oxygen-induced retinopathy

人视蛋白减少氧诱导视网膜病变小鼠模型中的病理性视网膜前新生血管形成

• 发表时间: 2017
• 作者: Izabela P Klaska