State Key Laboratory of Ophthalmology, Optometry, and Visual Science; Eye Hospital, Wenzhou Medical University, Wenzhou, China.
PriMed Non-human Primate Research Center of Sichuan PriMed Shines Bio-tech., Ltd., Ya'an, Sichuan Province, China.
Transl Vis Sci Technol. 2024 Aug 1;13(8):24. doi: 10.1167/tvst.13.8.24.
Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid β-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD.
CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys.
L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% ± 25.8% (P = 0.004) and 1.5% ± 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did.
This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV.
This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.
尽管抗血管内皮生长因子（VEGF）抗体的玻璃体内注射仍然是治疗渗出性年龄相关性黄斑变性（exAMD）的主要方法，但它的疗效有限。先前的研究表明，srr 的功能丧失突变和丝氨酸外消旋酶抑制剂 L-天冬氨酸 β-羟肟酸（L-ABH）的静脉内注射均可显著抑制小鼠的激光诱导脉络膜新生血管（CNV）。鉴于 L-ABH 是一种小分子，本研究探讨了通过滴眼给予 L-ABH 对 CNV 的影响，旨在开发 exAMD 的非侵入性治疗策略。
通过激光光凝在小鼠和恒河猴中建立 CNV 模型。将 7 只猴子随机分为生理盐水组或 L-ABH 滴眼剂组。腹腔或静脉内注射荧光素可使小鼠和猴子的 CNV 显影。荧光素眼底血管造影用于评估渗漏，而光学相干断层扫描用于测量猴子的视网膜厚度。
L-ABH 滴眼剂可显著减少激光损伤的小鼠的荧光素渗漏（与生理盐水相比，P < 0.001）。在激光损伤的恒河猴中，L-ABH 治疗的渗漏面积平均百分比变化分别为 2.5%±25.8%（P = 0.004）和 1.5%±75.7%（与生理盐水相比，P = 0.023）在第 14 天和第 28 天。然而，L-ABH 滴眼剂对 4 级激光点的数量或视网膜厚度没有显著影响，而贝伐单抗有影响。
本研究证明了 SRR 抑制剂在两种激光诱导的 CNV 动物模型中的潜在疗效。
温鹏辉
