Cammalleri Maurizio, Bagnoli Paola
Department of Biology, University of Pisa, 56123 Pisa, Italy.
Cells. 2025 Jul 18;14(14):1107. doi: 10.3390/cells14141107.
Retinal ischemia is implicated in ocular diseases involving aberrant neovessel proliferation that characterizes proliferative retinopathies. Their therapy still remains confined to the intravitreal administration of anti-vascular endothelial growth factor (VEGF) medication, which is limited by side effects and progressive reduction in efficacy. Mimicking neovascular diseases in rodents, although of great help for translating fundamental mechanistic findings and assessing therapeutic potential in humans, is limited by the rodent's short life span, which prevents retinal vessel proliferation over time. However, the oxygen-induced retinopathy (OIR) model, which mimics retinopathy of prematurity, seems to meet some criteria that are common to proliferative retinopathies. The present review provides insight into preclinical models and their suitability to mimic proliferative retinopathies. Further considerations will be applied to emerging approaches and advanced methodologies for the management of proliferative retinopathies, leading to the identification of new therapeutic targets, including our contribution in the field. Major emphasis is given to the possibility of using systemic therapies either alone or in combination with intravitreal anti-VEGF administration to maximize clinical benefits by combining drugs with different modes of action. This review is concluded by an in-depth discussion on future advancements and a critical view of preclinical finding translatability. Despite the major effort of preclinical and clinical research to develop novel therapies, the blockade of VEGF activity still remains the only treatment for proliferative retinopathies for more than twenty years since its first therapeutic application.
视网膜缺血与涉及异常新血管增殖的眼部疾病有关，这种异常新血管增殖是增殖性视网膜病变的特征。其治疗方法仍局限于玻璃体内注射抗血管内皮生长因子（VEGF）药物，但该方法存在副作用且疗效会逐渐降低。在啮齿动物中模拟新生血管疾病，虽然对转化基础机制研究结果和评估人类治疗潜力有很大帮助，但由于啮齿动物寿命较短，无法随着时间推移观察到视网膜血管增殖，因此受到限制。然而，模拟早产儿视网膜病变的氧诱导视网膜病变（OIR）模型似乎符合增殖性视网膜病变的一些共同标准。本综述深入探讨了临床前模型及其模拟增殖性视网膜病变的适用性。还将进一步考虑增殖性视网膜病变管理的新方法和先进技术，以确定新的治疗靶点，包括我们在该领域的贡献。主要强调单独使用全身治疗或与玻璃体内抗VEGF注射联合使用的可能性，通过结合不同作用方式的药物来最大化临床益处。本综述最后深入讨论了未来的进展，并对临床前研究结果的可转化性进行了批判性审视。尽管临床前和临床研究为开发新疗法付出了巨大努力，但自首次治疗应用以来的二十多年里，阻断VEGF活性仍然是增殖性视网膜病变的唯一治疗方法。
