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本文搬运自《Ophthalmology Times》 | ARVO 原作者：Sheryl Stevenson 原标题： ARVO 2026: Gene therapy and optogenetics show lasting vision improvement in retinitis pigmentosa（译：ARVO 2026：基因疗法和光遗传学显示视网膜色素变性患者的视力有持久改善） 主要要点MCO-010在52周时实现了~3个ETDRS线BCVA改善，并在剩余期维持至152周，支持晚期视网膜色素变性患者持久的功能益处。与眼底自体荧光相关的反应强度、转导证据、中心亚场厚度>100微米、OCT变薄减少及疾病持续时间<30年。DVC1-0401在36个月内无载体归因的严重不良事件;报告的严重事件大多与手术相关，包括白内障和流源性脱离。吊蜗牛PEDF治疗与BCVA和Humphrey 10-2中心凹敏感性显著下降较未治疗的眼匹相关，需更大规模对照试验确认。根据ARVO 2026年展示的数据，基因疗法和光遗传学均在视网膜色素变性患者中显示出持续的视觉益处，持续三年。（图片来源：AdobeStock/admin_design） 视网膜色素变性（RP）历来治疗手段十分有限，患者除低视力辅助器具外几乎无有效疗法，且感光细胞损伤大多被认为不可逆。2026 年 5 月 3 日至 7 日，在科罗拉多州丹佛市举办的ARVO 年度大会上，两项重磅研究发布三年临床随访数据，分别采用不同生物治疗路径，探索视网膜色素变性患者视功能保护与修复方案：光遗传学基因疗法与慢病毒载体神经保护疗法。 1. MCO-010光遗传学疗法：RESTORE/REMAIN项目三年最佳矫正视力持续获益 Vinit B. Mahajan医学博士、哲学博士及其同事报告了MCO-010（在晚期RP患者身上的REMAIN长期随访研究的三年结果。1CO-010是Nanoscope Therapeutics研发的光遗传学基因疗法，通过玻璃体腔注射2型腺相关病毒（AAV2），向双极细胞递送多特征视蛋白（MCO），绕过受损感光细胞重建光感知能力。该疗法不依赖患者具体基因突变类型，适用于各类病因的视网膜色素变性患者。 RESTORE是一项随机对照的2b/3期试验，晚期RP患者接受了一次高剂量（1.2×10）的玻璃体腔内注射 MCO-01011GC/EYE;n = 9），低剂量（0.9 × 1011GC/EYE;n = 9）或假控制（n = 9）。完成RESTORE的患者在第100周有资格继续进行REMAIN长期随访研究。RESTORE的主要终点为第52周时最佳矫正视力（BCVA）相较基线的变化。 数据显示，第52周，高剂量组BCVA相较基线的平均变化为0.337±0.083 LogMAR（对假组，P = 0.021），低剂量组为0.382± 0.124 LogMAR（对假组，P = 0.029）。REMAIN第152周，BCVA较基线平均改善为0.264±高剂量组0.112 LogMAR，低剂量组为0.453±0.140 LogMAR。作者报告称，这些改善大约对应3条ETDRS视线的增益。未报告治疗相关的严重不良事件。 事后多因素分析发现，眼底自发荧光成像显示的MCO-010表达水平、基线黄斑中心凹厚度大于100μm、病程少于30年，是影响治疗应答的关键利好因素。视力提升幅度与视网膜转染水平、MCO蛋白表达、视网膜变薄程度及病程长短高度相关。 作者称该研究是全球首个随机对照临床试验证实RP患者视力可获得三年持续性临床获益，同时证实药物表达水平、眼部基线结构及病程时长，是预判疗效的重要参考指标。 2. DVC1-0401神经保护基因疗法：36个月安全性与视功能保护结果 村上雄介医学博士、哲学博士及其同事报告了DVC1-0401 1/2a 期研究者发起临床试验 36 个月随访数据。2  DVC1-0401为第三代非复制型慢病毒载体，可编码视网膜天然表达的色素上皮衍生因子（PEDF），发挥神经保护作用。 与MCO-010通过针对残留的双极细胞恢复光敏感不同，DVC1-0401不重建视力，而是通过神经保护延缓感光细胞退行性病变。该试验在日本进行，摘要中未登记公开的试验登记号。 这是一项单臂、开放标签、剂量递增试验，纳入12名典型RP患者，不限基因分型，最佳矫正视力区间为20/200～20/20。所有受试者均在视力较差眼接受视网膜下注射，分为低、中、高三个剂量组，每组4人。试验先完成12个月主要观察期，随后进入长达36个月的长期随访。 随访期间，12名受试者均未出现与DVC1-0401相关的严重不良事件。试验观察期内出现5起严重不良事件，包括3例白内障、1例裂孔性视网膜脱离、1例持续性视网膜下积液，均归因于手术操作而非药物本身；随访期另出现1例黄斑裂孔、对侧未治疗眼出现1例白内障。 利用线性混合效应模型，研究人员发现治疗眼的BCVA和Humphrey 10-2中心凹视网膜敏感性下降速度显著低于其他眼（P 率<0.05）。作者指出，功能衰退率降低可能暗示DVC1-0401具有神经保护作用，同时提醒小样本量和单臂设计值得在未来关键试验中验证。 值得关注的是，本试验不限基因突变类型入组，意味着该神经保护疗法有望适用于所有异质性 RP 患者群体，无需针对特定突变定制治疗方案。 行业展望 本次 ARVO 大会两项三年随访研究，代表视网膜色素变性两大全新治疗路径：光遗传学疗法实现视力长期稳定提升、神经保护基因疗法延缓视功能衰退。两款疗法目前均处于早期研发阶段，后续仍需更大规模确证性临床试验，才能正式确立临床应用地位。 参考文献 Mahajan VB, Zak V, Bergstrom L, et al. Optogenetic REMAIN 3-year study data: lasting vision improvement with MCO-010 in the RESTORE phase 2b/3 trial for retinitis pigmentosa. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 2516.Murakami Y, Hisai T, Mawatari G, et al. Long-term outcomes of lentivirus-based neuroprotective gene therapy for retinitis pigmentosa: a phase I/IIa investigator-initiated clinical trial of DVC1-0401. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 2517.原文链接：https://www.ophthalmologytimes.com/view/arvo-2026-gene-therapy-and-optogenetics-show-lasting-vision-improvement-in-retinitis-pigmentosa声明本文相关生物医药及眼科领域产业新闻内容，由AI工具辅助完成网络信息搜集与整理工作。内容整理过程中已对信息来源及准确性进行核查，但AI生成内容可能存在疏漏，敬请谅解。本文仅传递产业资讯，不提供医疗、投资建议。鉴于互联网的开放性和文章创作的复杂性，我们无法保证所转载的所有文章均已获得原作者的明确授权。如果您是原作者或拥有相关权益，请与我们联系，我们将立即删除未经授权的文章。本声明旨在保障信息透明度，AI工具仅为辅助手段，不享有相关内容的著作权及署名权。

Interim data from a GPCR-based optogenetic gene therapy add early human evidence to a mutation-agnostic approach for end-stage retinitis pigmentosa, a disease for which no broadly applicable approved treatment exists. Restore Vision Inc., a Tokyo-based clinical-stage biotechnology company, announced interim results from its Phase I/II trial of RV-001 optogenetic gene therapy, with data from six patients followed for up to 168 days. The open-label, dose-escalation study enrolled patients with no light perception across two cohorts of three patients each. All participants received a single intravitreal injection of RV-001, an adeno-associated virus vector encoding a chimeric rhodopsin designed to re-sensitize surviving inner retinal neurons to light. The primary endpoint is safety; exploratory assessments include visual acuity by logMAR chart, full-field stimulus testing, and functional vision tasks such as mobility and object recognition. No dose-limiting toxicities or drug-related serious adverse events were reported in either cohort. In the high-dose group, all three patients progressed from no light perception to light perception or better within one month, and one patient achieved chart-based visual acuity measurable by the Berkeley Rudimentary Vision Test. In the low-dose cohort, one of three patients reached light perception at approximately three months. The study remains ongoing, and the company said it plans to expand data collection across broader patient populations. Results were presented at Eyecelerator at ARVO 2026 and the Retinal Therapeutics Innovation Summit on May 1, 2026. Retinitis pigmentosa is caused by mutations in more than 70 genes, all converging on progressive rod and then cone photoreceptor degeneration. By the time patients reach the no-light-perception stage targeted in this trial, photoreceptors are largely absent, but downstream retinal interneurons — including bipolar and ganglion cells — often remain viable. That anatomical reality underpins the optogenetic approach: rather than replacing or correcting the causative mutation, the strategy is to render surviving inner retinal neurons light-sensitive by expressing an exogenous photosensitive protein. RV-001 delivers a chimeric rhodopsin that combines the cytoplasmic loops of vertebrate rhodopsin, which couple to native G-proteins and activate the endogenous phototransduction cascade, with the transmembrane scaffold of microbial rhodopsin, which confers self-regenerating chromophore properties independent of the retinal pigment epithelium visual cycle. The GPCR gene therapy design is intended to exploit signal amplification inherent to G-protein signaling, potentially enabling light detection under natural ambient conditions without external devices — a practical limitation of earlier channelrhodopsin-based approaches that required high-intensity light stimulation or goggles. The only approved gene therapy for any form of retinitis pigmentosa remains voretigene neparvovec (Luxturna, Spark Therapeutics), which targets biallelic RPE65 mutations — a subtype affecting roughly 1%–2% of RP patients. For the remaining patient population, no pharmacological or gene-based treatment has received regulatory approval. Supportive measures such as vitamin A supplementation and low-vision aids address neither disease progression nor restoration of function in advanced disease. The practical consequence is that patients with end-stage RP and no light perception — the population enrolled in this trial — currently have no therapeutic options. Mutation-specific gene replacement strategies are also largely inapplicable at this disease stage, as they depend on viable photoreceptors to rescue. This gap frames the clinical rationale for mutation-agnostic, restorative approaches such as optogenetic therapy for retinal disease. The field of optogenetic therapy for retinal disease has attracted multiple developers, with strategies diverging primarily on the choice of photosensitive protein and whether external devices are required. Nanoscope Therapeutics has advanced MCO-010, an AAV-delivered multi-characteristic opsin, into late-stage clinical development for RP, with randomized data reported. GenSight Biologics pursued GS030, a channelrhodopsin-based AAV therapy paired with light-stimulating goggles, in earlier human studies. Bionic Sight evaluated a channelrhodopsin program in advanced RP. All three rely on microbial ion channels rather than GPCR-mediated signaling, which the Restore Vision clinical trial results position as a mechanistic differentiator, at least theoretically. The interim Restore Vision clinical trial results are early-stage and drawn from a small, uncontrolled cohort. The convergence of signals across visual acuity, full-field stimulus testing, and functional vision tasks is notable given the severity of baseline impairment, but the data do not yet establish the durability, magnitude, or clinical meaningfulness of any functional gains. Expansion to broader patient populations, as the company has indicated, will be necessary to assess whether the GPCR gene therapy approach translates beyond this initial cohort. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. 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