State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Exp Eye Res. 2019 Jul;184:1-7. doi: 10.1016/j.exer.2019.03.020. Epub 2019 Mar 27.
The laser-induced choroidal neovascularization (CNV) model in nonhuman primates has played a critical role in the development of new therapies for neovascular age-related macular degeneration. The widespread use of this model, however, has been limited by its high costs, mainly due to the lower efficiency of animal use. We optimized the CNV model by administering repeated photocoagulation treatments to the same eye of each animal, and preliminarily evaluated this model using an assessment of the efficacy of an anti-vascular endothelial growth factor (VEGF) agent to address this problem. Seven rhesus monkeys were included and divided into two groups, which were named the laser-only and laser-bevacizumab groups. Each animal underwent 3 retinal photocoagulation sessions in the same eye at 4-week intervals to induce CNV. Three weeks after the first laser treatment, the animals in the laser-bevacizumab group were administered an intravitreal injection of bevacizumab. Fluorescein angiography (FA) was performed in all animals at multiple time points within 12 weeks to assess the severity and development of CNV following each laser treatment. The laser lesions produced in each photocoagulation session were analysed separately using grading and densitometry methods, and CNV severity was represented by the CNV incidence and the mean integrated fluorescence intensity (MIFI), respectively. Our results showed that in the animals in the laser-only group, the average CNV incidence rates were 62.5%, 42% and 50% at 2 weeks after each laser treatment, and the average MIFI values (x10) were 3.83 ± 2.36, 2.66 ± 1.42 and 2.52 ± 0.18, respectively. No significant differences were found among treatments. After week 2, the CNVs progressed or regressed continuously over 2-6 weeks before stabilization, and the time course of CNV development in each animal was generally the same after each photocoagulation session. In the laser-bevacizumab group, however, the average CNV incidence rates of each laser treatment at week 2 were 50%, 0 and 37.5%, respectively, and the average MIFI values were 3.79 ± 0.47, 1.09 ± 0.35 and 2.37 ± 1.35, respectively. The differences between treatments 1 and 2 were statistically significant. Meanwhile, the CNVs induced by laser treatment 1, which progressed during weeks 2-3, were reduced after bevacizumab administration. The average CNV incidence decreased from 50% at week 3 to 4.2% at week 4, and the average MIFI decreased from 4.62 ± 1.15 to 1.76 ± 0.81, both of which were statistically significant. On the other hand, the CNVs induced by treatments 2 and 3 did not show any significant changes over time. Our study demonstrated that repeated retinal photocoagulation in the monkey eye produces relatively consistent CNVs, which can be used to assess the efficacies of anti-angiogenic agents more efficiently.
激光诱导的脉络膜新生血管（CNV）模型在非人类灵长类动物中对于治疗新生血管性年龄相关性黄斑变性的新疗法的发展起到了关键作用。然而，由于动物利用率低，该模型的广泛应用受到了限制，这主要是因为其成本高昂。为了解决这个问题，我们通过对同一只眼进行重复光凝治疗来优化 CNV 模型，并初步使用抗血管内皮生长因子（VEGF）药物的疗效评估来评估该模型。纳入了 7 只恒河猴，将其分为激光治疗组和激光贝伐单抗组。每组动物在 4 周的间隔内接受 3 次视网膜光凝治疗，以诱导 CNV。第一次激光治疗后 3 周，激光贝伐单抗组的动物接受了玻璃体腔内注射贝伐单抗。在 12 周内的多个时间点对所有动物进行荧光素眼底血管造影（FA）检查，以评估每次激光治疗后 CNV 的严重程度和发展情况。使用分级和密度测量方法分别分析每次光凝治疗产生的激光损伤，并分别用 CNV 发生率和平均积分荧光强度（MIFI）表示 CNV 的严重程度。我们的结果表明，在激光治疗组的动物中，每次激光治疗后 2 周的平均 CNV 发生率分别为 62.5%、42%和 50%，平均 MIFI 值（x10）分别为 3.83±2.36、2.66±1.42 和 2.52±0.18。各治疗组之间无显著差异。在第 2 周之后，CNV 在 2-6 周内持续进展或消退，然后在稳定之前再次进展。在每次光凝治疗后，每个动物的 CNV 发展过程通常是相同的。然而，在激光贝伐单抗组中，每次激光治疗第 2 周的平均 CNV 发生率分别为 50%、0%和 37.5%，平均 MIFI 值分别为 3.79±0.47、1.09±0.35 和 2.37±1.35。治疗 1 和 2 之间的差异具有统计学意义。同时，激光治疗 1 诱导的 CNV 在第 2-3 周内进展，在贝伐单抗给药后减少。CNV 的平均发生率从第 3 周的 50%下降到第 4 周的 4.2%，平均 MIFI 从 4.62±1.15 下降到 1.76±0.81，均具有统计学意义。另一方面，治疗 2 和 3 诱导的 CNV 随时间无明显变化。我们的研究表明，在猴眼内重复进行视网膜光凝可产生相对一致的 CNV，这可更有效地评估抗血管生成药物的疗效。
