Abstract
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.
Highlights
Age-related macular degeneration (AMD) is a leading cause of visual loss across the world
Anti-VEGF rani was applied to photodynamic therapy (PDT)-exposed cells at various doses (25, 50, 75, 100, 125, and 150 μg/mL) and at different time points (6, 48 h before PDT or 6 h after PDT), and cell viability was detected as described above at 12 h after PDT
It indicates that pre- compared to post-treatment with rani significantly aggravates PDT injury in RF/6A cells, and we chose the dose of 125 μg/mL in the subsequent experiments
Summary
Age-related macular degeneration (AMD) is a leading cause of visual loss across the world. AMD in Asians differs from that in Westerns in terms of epidemiology, pathogenesis, clinical presentation and treatment (Lim et al, 2013). Polypoidal choroidal vasculopathy (PCV) is the predominant subtype of exudative AMD in Asians, in contrast to choroidal neovascularization (CNV) secondary to AMD in Caucasian populations. Those two subtypes respond quite differently to treatments. The standard of care for CNV-AMD is antivascular endothelial growth factor (anti-VEGF) therapy, whereas the optimal treatment guidelines for PCV have not been well established. It is projected that Asia will contribute the highest global prevalence of AMD by 2040 (Wong et al, 2014), it is necessary and urgent to develop better treatment for PCV
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call