Levodopa Positively Affects Neovascular Age-Related Macular Degeneration.
Levodopa Positively Affects Neovascular Age-Related Macular Degeneration.
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DOI：
10.1016/j.amjmed.2020.05.038
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Snyder RW
中科院分区：
文献类型：
--
作者：
Figueroa AG;Boyd BM;Christensen CA;Javid CG;McKay BS;Fagan TC;Snyder RW
年龄相关性黄斑变性（AMD）是全世界失明的常见原因。新生血管性 AMD (nAMD) 是该疾病的一种晚期形式，其中过量的血管内皮生长因子 (VEGF) 会诱导新血管生长并渗漏液体，占 AMD 视力丧失的 90%。视网膜色素上皮功能障碍可能引发 AMD。视网膜色素上皮细胞表达 G 蛋白偶联受体 GPR143，该受体可响应左旋多巴下调 VEGF。抗 VEGF 疗法可有效治疗 nAMD，这表明过度的 VEGF 活性驱动了这种病理。在一项开放标签试点研究中，在新诊断的 nAMD 且未接受过抗 VEGF 注射的患者（队列 1）中，评估了卡比多巴-左旋多巴对视力和解剖结果的影响，为期 4 周。然后对患者进行 5 个月的随访，增加左旋多巴剂量。先前接受抗 VEGF 注射疗法（队列 2）的患者也接受递增左旋多巴剂量的治疗，并进行为期 6 个月的评估。左旋多巴安全、耐受性良好，可延迟抗 VEGF 注射治疗，同时改善视力结果。在第一个月，未经抗 VEGF 治疗，视网膜液减少了 29%（P = .02，n = 12）。 6 个月内，视网膜液持续减少，平均注射频率为 0.38 次/月。第 6 个月时，队列 1 的平均视力提高了 4.7 个字母（P = .004，n = 15），队列 2 的平均视力提高了 4.8 个字母（P = .02，n = 11）。此外，第 2 组中抗 VEGF 注射的需求减少了 52% (P = .002)。我们的研究结果表明，在未来的研究中，GPR143 与左旋多巴联合治疗 nAMD 的药理学靶向作用有效并支持。
Age-related macular degeneration (AMD) is a common cause of blindness worldwide. Neovascular AMD (nAMD) is an advanced form of the disease, in which excess vascular endothelial growth factor (VEGF) induces growth of new blood vessels that leak fluid, accounting for 90% of vision loss in AMD. Dysfunction of the retinal pigment epithelium likely initiates AMD. Retinal pigment epithelial cells express a G protein-coupled receptor, GPR143, which downregulates VEGF in response to levodopa. Anti-VEGF therapy effectively treats nAMD, suggesting that excessive VEGF activity drives the pathology. In an open-label pilot study, in patients with newly diagnosed nAMD and naïve to anti-VEGF injections (Cohort-1), the effects of carbidopa-levodopa on vision and anatomic outcomes were evaluated for 4 weeks. Then patients were followed 5 months further with ascending levodopa doses. Patients previously treated with anti-VEGF injection therapy (Cohort-2) were also treated with ascending levodopa doses and evaluated for 6 months. Levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29% (P = .02, n = 12) without anti-VEGF treatment. Through 6 months the decrease in retinal fluid was sustained, with a mean frequency of 0.38 injections/month. At month 6, mean visual acuity improved by 4.7 letters in Cohort-1 (P = .004, n = 15) and by 4.8 letters in Cohort-2 (P = .02, n = 11). Additionally, there was a 52% reduction in the need for anti-VEGF injections in Cohort-2 (P = .002). Our findings suggest efficacy and support the pharmacological targeting of GPR143 with levodopa for the treatment of nAMD in future studies.
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