Role of inflammasome activation in neovascular age-related macular degeneration.
Role of inflammasome activation in neovascular age-related macular degeneration.
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DOI：
10.1111/febs.16278
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发表时间：
2023-01
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--
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目前的抗vegf - a疗法可抑制一部分新生血管性年龄相关性黄斑变性（NV-AMD）患者的脉络膜新生血管（CNV）。然而，这种抗VEGF-A疗法的长期治疗可能会损害绒毛膜毛细血管和视网膜的生理功能，而这正是VEGF-A所需要的。此外，尽管持续抗vegf - a治疗，疾病仍可能发生进展。因此，迫切需要针对特异性疾病相关机制的新型NV-AMD治疗方法，而不损害视网膜和脉络膜稳态功能所需的生长因子和细胞通路。抑制促进CNV的炎症途径将是一种很有前途的新方法，可能不会干扰健康视网膜和脉络膜细胞的正常功能。在这种情况下，炎性小体是一种促炎蛋白复合物，主要通过生成IL-1β促进病理性血管生成，据报道，它在AMD中被激活，已成为AMD领域的一个非常感兴趣的领域。然而，大多数研究主要集中在视网膜色素上皮细胞（RPE）中的NLRP3炎症小体上，并且相互矛盾的发现导致炎症小体在AMD发病机制中的作用尚不清楚。最近的数据表明，炎性体在活化的巨噬细胞和视网膜小胶质细胞中激活，而在RPE细胞中不激活，可促进CNV。此外，尽管缺乏NLRP3， CNV巨噬细胞和小胶质细胞也可能发生炎性体活化。因此，巨噬细胞/小胶质细胞中CNV形成部位的NLRP3炎性小体和非NLRP3炎性小体的激活都可能促进NV-AMD。
Current anti-VEGF-A therapies inhibit choroidal neovascularization (CNV) in a subset of patients with neovascular age-related macular degeneration (NV-AMD). However, long-term treatment with such anti-VEGF-A therapies may impair physiological functions of the choriocapillaris and retina for which VEGF-A is needed. Moreover, disease progression can occur despite continuous anti-VEGF-A treatment. Thus, novel therapies for NV-AMD are urgently needed that target specifically disease-associated mechanisms without impairing growth factors and cellular pathways that are required for homeostatic functions of the retina and choroid. Inhibiting the inflammatory pathways that promote CNV would be such a promising novel approach that would likely not interfere with the normal functions of healthy retinal and choroidal cells. In this context, the inflammasome, a proinflammatory protein complex that promotes pathologic angiogenesis largely through generation of IL-1β and which has been reported to be activated in AMD, has become an area of much interest in the AMD field. However, most studies have focused mainly on the NLRP3 inflammasome in retinal pigment epithelial cells (RPE), and conflicting findings have resulted in an unclear picture of the role of the inflammasome for AMD pathogenesis. Recent data suggest that inflammasome activation in activated macrophages and retinal microglia but not in RPE cells promotes CNV. Furthermore, inflammasome activation can occur in CNV macrophages and microglia despite lack of NLRP3. Thus, activation of both NLRP3 inflammasomes as well as non-NLRP3 inflammasomes in macrophages/microglia at sites of CNV formation likely promote NV-AMD.
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影响因子：
5.6
作者：
Wang Y;Hanus JW;Abu-Asab MS;Shen D;Ogilvy A;Ou J;Chu XK;Shi G;Li W;Wang S;Chan CC
通讯作者：
Chan CC
影响因子：
7.7
作者：
Malsy J;Alvarado AC;Lamontagne JO;Strittmatter K;Marneros AG
通讯作者：
Marneros AG
影响因子：
6
作者：
He, Lizhi;Marneros, Alexander G.
通讯作者：
Marneros, Alexander G.
影响因子：
13.7
作者：
Rofagha, Soraya;Bhisitkul, Robert B.;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
64.5
作者：
Tarallo V;Hirano Y;Gelfand BD;Dridi S;Kerur N;Kim Y;Cho WG;Kaneko H;Fowler BJ;Bogdanovich S;Albuquerque RJ;Hauswirth WW;Chiodo VA;Kugel JF;Goodrich JA;Ponicsan SL;Chaudhuri G;Murphy MP;Dunaief JL;Ambati BK;Ogura Y;Yoo JW;Lee DK;Provost P;Hinton DR;Núñez G;Baffi JZ;Kleinman ME;Ambati J
通讯作者：
Ambati J