Polypoidal choroidal vasculopathy (PCV) is the predominant subtype of exudative age-related macular degeneration in Asians. Although photodynamic therapy (PDT) is widely used for PCV treatment, its long-term beneficial effects are unsatisfactory. Accumulating clinical investigations suggest that combined therapy with anti-vascular endothelial growth factor (anti-VEGF) and PDT is superior to PDT monotherapy. However, the optimal time of anti-VEGF before or after PDT remains controversial, hence it needs to further explore the mechanism underlying combined therapy. PDT causes selective damage to endothelial cells, which determines its angio-occlusive efficiency, yet the impact of anti-VEGF on PDT-induced endothelial injury is unclear. Here, we found that pre- compared to post-treatment with anti-VEGF ranibizumab (rani) significantly aggravates PDT injury in the rhesus macaque choroid-retinal endothelial (RF/6A) cell line. PDT activates apoptosis, necroptosis and NLRP3 inflammasome in RF/6A cells. Pre-treatment with rani promotes PDT-caused apoptosis via triggering caspase 8-mediated extrinsic apoptosis, and caspase 8 might also play a pivotal role in the rani’s function of suppressing PDT-induced necroptosis and NLRP3 inflammasome activation. Our results implicate that pre-treatment with rani may enhance the angio-occlusive efficiency of PDT and alleviate endothelial inflammatory response, which gives it a great advantage over post-treatment.

息肉样脉络膜血管病（PCV）是亚洲人与年龄相关的渗出性黄斑变性的主要亚型。尽管光动力疗法（PDT）已广泛用于PCV治疗，但其长期有益效果仍不能令人满意。越来越多的临床研究表明，抗血管内皮生长因子（anti-VEGF）和PDT的联合治疗优于PDT单一疗法。然而，PDT之前或之后抗VEGF的最佳时间仍存在争议，因此需要进一步探讨联合治疗的机制。PDT对内皮细胞造成选择性损伤，这决定了它的血管闭塞效率，但抗VEGF对PDT诱导的内皮损伤的影响尚不清楚。这里，我们发现，与抗VEGF雷珠单抗（rani）进行治疗后相比，猕猴猕猴脉络膜-视网膜内皮细胞（RF / 6A）的PDT损伤明显加重。PDT激活RF / 6A细胞的凋亡，坏死性坏死和NLRP3炎性小体。用rani预处理可通过触发caspase 8介导的外在凋亡来促进PDT引起的凋亡，而caspase 8可能在rani抑制PDT诱导的坏死病和NLRP3炎症小体激活中起关键作用。我们的结果表明，兰尼预处理可以增强PDT的血管闭塞效率并减轻内皮炎症反应，这比后处理具有更大的优势。坏死和RF / 6A细胞中的NLRP3炎性小体。用rani预处理可通过触发caspase 8介导的外在凋亡来促进PDT引起的凋亡，而caspase 8可能在rani抑制PDT诱导的坏死病和NLRP3炎症小体激活中起关键作用。我们的结果表明，兰尼预处理可以增强PDT的血管闭塞效率并减轻内皮炎症反应，这比后处理具有更大的优势。坏死和RF / 6A细胞中的NLRP3炎性小体。用rani预处理可通过触发caspase 8介导的外在凋亡来促进PDT引起的凋亡，而caspase 8可能在rani抑制PDT诱导的坏死病和NLRP3炎症小体激活中起关键作用。我们的结果表明，兰尼预处理可以增强PDT的血管闭塞效率并减轻内皮炎症反应，这比后处理具有更大的优势。