LRG1 as a novel therapeutic target in eye disease.
LRG1 as a novel therapeutic target in eye disease.
复制标题
LRG1作为眼科疾病的新治疗靶点
DOI：
10.1038/s41433-021-01807-4
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Moss SE
中科院分区：
文献类型：
--
作者：
De Rossi G;Da Vitoria Lobo ME;Greenwood J;Moss SE
视网膜和脉络膜疾病是发达国家失明和视力受损的主要原因，而且由于人口老龄化和糖尿病流行而呈上升趋势。护理的标准是以阻断血管内皮生长因子(VEGF)为中心，但尽管使失明患者数量减少了一半，但患者无反应率高和随着时间的推移失去疗效是关键挑战。血管稳态失调，再加上纤维化和炎症，是导致威胁视力的眼病的主要原因。提高我们对这些病理过程的了解应该有助于新药的开发，以解决患者目前的临床挑战。富含亮氨酸的α-2糖蛋白1(LRG1)是血管功能障碍、炎症和纤维化的一个新的关键因子。在生理条件下，LRG1在肝脏和粒细胞中有结构性表达，但对其正常生物学功能知之甚少。在糖尿病视网膜病变(DR)和新生血管年龄相关性黄斑变性(NvAMD)等病理场景中，它的表达异位上调，并获得了更好的致病作用。对转化生长因子β(转化生长因子β)途径的上下文依赖性调节是LRG1的主要活动之一，但最近还出现了更多的作用。这篇综述旨在强调LRG1在血管视网膜病变中的致病作用的临床和临床前证据，以及从其他疾病推断可能与眼部疾病相关的功能。最后，我们将提供治疗nvAMD的抗LRG1疗法的最新进展。
Retinal and choroidal diseases are major causes of blindness and visual impairment in the developed world and on the rise due to an ageing population and diabetes epidemic. Standard of care is centred around blockade of vascular endothelial growth factor (VEGF), but despite having halved the number of patients losing sight, a high rate of patient non-response and loss of efficacy over time are key challenges. Dysregulation of vascular homoeostasis, coupled with fibrosis and inflammation, are major culprits driving sight-threatening eye diseases. Improving our knowledge of these pathological processes should inform the development of new drugs to address the current clinical challenges for patients. Leucine-rich α-2 glycoprotein 1 (LRG1) is an emerging key player in vascular dysfunction, inflammation and fibrosis. Under physiological conditions, LRG1 is constitutively expressed by the liver and granulocytes, but little is known about its normal biological function. In pathological scenarios, such as diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD), its expression is ectopically upregulated and it acquires a much better understood pathogenic role. Context-dependent modulation of the transforming growth-factor β (TGFβ) pathway is one of the main activities of LRG1, but additional roles have recently been emerging. This review aims to highlight the clinical and pre-clinical evidence for the pathogenic contribution of LRG1 to vascular retinopathies, as well as extrapolate from other diseases, functions which may be relevant to eye disease. Finally, we will provide a current update on the development of anti-LRG1 therapies for the treatment of nvAMD.
登录
查看更多内容
DOI：
10.1038/s41433-020-0895-z
发表时间：
2020-11
期刊：
Eye (London, England)
影响因子：
--
作者：
Adamis AP;Brittain CJ;Dandekar A;Hopkins JJ
通讯作者：
Hopkins JJ
影响因子：
40.5
作者：
Antonetti, David A.;Silva, Paolo S.;Stitt, Alan W.
通讯作者：
Stitt, Alan W.
影响因子：
16.6
作者：
Dejana E;Hirschi KK;Simons M
通讯作者：
Simons M
影响因子：
168.9
作者：
Dimaras, Helen;Kimani, Kahaki;Gallie, Brenda L.
通讯作者：
Gallie, Brenda L.
影响因子：
13.7
作者：
Dugel, Pravin U.;Koh, Adrian;Holz, Frank G.
通讯作者：
Holz, Frank G.