Kamuvudine-9 Protects Retinal Structure and Function in a Novel Model of Experimental Rhegmatogenous Retinal Detachment.
Kamuvudine-9 Protects Retinal Structure and Function in a Novel Model of Experimental Rhegmatogenous Retinal Detachment.
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Kamuvudine-9在新型实验性rhegmatogentos视网膜脱离模型中保护视网膜结构和功能。
DOI：
10.1167/iovs.64.5.3
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发表时间：
2023-05-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
孔源性视网膜脱离（RRD）是一种威胁视力的事件，可通过手术干预获益。在等待手术复位期间，视网膜经常会发生不可逆的缺氧和炎症损伤。保护光感受器的临时疗法可以改善功能结果。我们试图确定抑制炎症小体激活的核苷逆转录酶抑制剂 (NRTI) 衍生物 Kamuvudine-9 (K-9) 以及 NRTI 拉米夫定 (3TC) 和叠氮胸苷 (AZT) 是否可以在 RRD 后保护视网膜。通过视网膜下注射 (SRI) 1% 羧甲基纤维素 (CMC) 在小鼠中诱导 RRD。为了模拟 RRD 临床管理后的结果，我们确定了 CMC 的 SRI 诱导自发性视网膜复位 (SRR) 在 10 天内发生的最佳条件 (RRD/SRR)。 K-9、3TC 或 AZT 通过腹腔注射给药。通过裂解的 caspase-1、IL-18 和裂解的 caspase-8 的丰度来监测炎症小体激活途径，并通过 TUNEL 染色评估光感受器死亡。通过全视野暗视视网膜电图评估视网膜功能。 RRD 诱导小鼠视网膜炎症小体激活和光感受器死亡。全身施用 K-9、3TC 或 AZT 可抑制视网膜炎性体激活和光感受器死亡。在 RRD/SRR 模型中，K-9 在 RRD 期间保护视网膜电功能，并在视网膜重新附着后引起改善。 K-9 和 NRTI 在实验性 RRD 中表现出抗炎和神经保护活性。鉴于 K-9 能够在 RRD 期间保护光感受器功能并增强重新附着后的视网膜功能，因此它显示出作为视网膜神经保护剂的前景，并值得在 RRD 中进行研究。此外，这种新颖的 RRD/SRR 模型可以促进与 RRD 相关的功能结果的实验评估。
Rhegmatogenous retinal detachment (RRD) is a vision-threatening event that benefits from surgical intervention. While awaiting surgical reattachment, irreversible hypoxic and inflammatory damage to the retina often occurs. An interim therapy protecting photoreceptors could improve functional outcomes. We sought to determine whether Kamuvudine-9 (K-9), a derivative of nucleoside reverse transcriptase inhibitors (NRTIs) that inhibits inflammasome activation, and the NRTIs lamivudine (3TC) and azidothymidine (AZT) could protect the retina following RRD. RRD was induced in mice via subretinal injection (SRI) of 1% carboxymethylcellulose (CMC). To simulate outcomes following the clinical management of RRD, we determined the optimal conditions by which SRI of CMC induced spontaneous retinal reattachment (SRR) occurs over 10 days (RRD/SRR). K-9, 3TC, or AZT was administered via intraperitoneal injection. Inflammasome activation pathways were monitored by abundance of cleaved caspase-1, IL-18, and cleaved caspase-8, and photoreceptor death was assessed by TUNEL staining. Retinal function was assessed by full-field scotopic electroretinography. RRD induced retinal inflammasome activation and photoreceptor death in mice. Systemic administration of K-9, 3TC, or AZT inhibited retinal inflammasome activation and photoreceptor death. In the RRD/SRR model, K-9 protected retinal electrical function during the time of RRD and induced an improvement following retinal reattachment. K-9 and NRTIs exhibit anti-inflammatory and neuroprotective activities in experimental RRD. Given its capacity to protect photoreceptor function during the period of RRD and enhance retinal function following reattachment, K-9 shows promise as a retinal neuroprotectant and warrants study in RRD. Further, this novel RRD/SRR model may facilitate experimental evaluation of functional outcomes relevant to RRD.
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影响因子：
2.3
作者：
Gange, William S.;Qiao, James B.;Bu, Ping
通讯作者：
Bu, Ping
影响因子：
4.2
作者：
Arroyo, JG;Yang, L;Chen, DF
通讯作者：
Chen, DF
影响因子：
13.6
作者：
Fukuda S;Narendran S;Varshney A;Nagasaka Y;Wang SB;Ambati K;Apicella I;Pereira F;Fowler BJ;Yasuma T;Hirahara S;Yasuma R;Huang P;Yerramothu P;Makin RD;Wang M;Baker KL;Marion KM;Huang X;Baghdasaryan E;Ambati M;Ambati VL;Banerjee D;Bonilha VL;Tolstonog GV;Held U;Ogura Y;Terasaki H;Oshika T;Bhattarai D;Kim KB;Feldman SH;Aguirre JI;Hinton DR;Kerur N;Sadda SR;Schumann GG;Gelfand BD;Ambati J
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Ambati J
影响因子：
9
作者：
Kong, Hui;Zhao, Hongran;Chen, Tianran;Song, Yanling;Cui, Yan
通讯作者：
Cui, Yan
影响因子：
4.2
作者：
Mervin, K;Valter, K;Stone, J
通讯作者：
Stone, J