VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models'
VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models'
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DOI：
10.1172/jci.insight.120231
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发表时间：
2018-05-17
期刊：
影响因子：
8
通讯作者：
Campochiaro, Peter A.
中科院分区：
文献类型：
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作者：
Long, Da;Kanan, Yogita;Campochiaro, Peter A.
眼内注射vegf中和蛋白对年龄相关性黄斑变性（AMD）引起的脉络膜新生血管（NV）患者有巨大的益处，但在治疗过程中，一些患者出现视网膜萎缩。一个临床试验组认为VEGF是视网膜神经元的一种存活因子，并将视网膜萎缩归因于VEGF抑制，并告诫不要频繁注射抗VEGF。这一建议可能会导致临床实践中治疗不足的不良结果。3型脉络膜NV患者视网膜萎缩的风险特别高，这是一个无法解释的观察结果。在此，我们在小鼠模型中表明，VEGF信号对光感受器的存活和功能没有贡献：(a)中和VEGFR2强烈抑制脉络膜NV，而不影响光感受器的功能或存活；(b) VEGF不能减缓遗传性视网膜变性小鼠的光感受器功能丧失或死亡，VEGF抑制也不会加重视网膜变性；(c) 3型脉络膜NV小鼠由于氧化损伤而发生视网膜萎缩，而VEGF抑制没有任何作用。眼内注射vegf中和蛋白是一种对新生血管性AMD患者非常有效的治疗方法，不应该因为担心它们可能导致视网膜萎缩导致长期视力丧失而拒绝或减少。
Intraocular injections of VEGF-neutralizing proteins provide tremendous benefits in patients with choroidal neovascularization (NV) due to age-related macular degeneration (AMD), but during treatment some patients develop retinal atrophy. Suggesting that VEGF is a survival factor for retinal neurons, a clinical trial group attributed retinal atrophy to VEGF suppression and cautioned against frequent anti-VEGF injections. This recommendation may contribute to poor outcomes in clinical practice from insufficient treatment. Patients with type 3 choroidal NV have particularly high risk of retinal atrophy, an unexplained observation. Herein we show in mouse models that VEGF signaling does not contribute to photoreceptor survival and functioning: (a) neutralization of VEGFR2 strongly suppresses choroidal NV without compromising photoreceptor function or survival; (b) VEGF does not slow loss of photoreceptor function or death in mice with inherited retinal degeneration, and there is no exacerbation by VEGF suppression; and (c) mice with type 3 choroidal NV develop retinal atrophy due to oxidative damage with no contribution from VEGF suppression. Intraocular injections of VEGF-neutralizing proteins, a highly effective treatment in patients with neovascular AMD, should not be withheld or reduced due to concern that they may contribute to long-term visual loss from retinal atrophy.