Pre-treatment With Ranibizumab Aggravates PDT Injury and Alleviates Inflammatory Response in Choroid-Retinal Endothelial Cells

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.

LS-HB-Mediated Photodynamic Therapy Inhibits Proliferation and Induces Cell Apoptosis in Melanoma

“…48 In addition, PDT activates the immune system and induces an inflammatory and immune response against tumor cells. 49 After illumination, local edema was observed in the irradiation site of mice in the LS-HB PDT experimental group (Figure 7A). This response is an intense, acute inflammatory response induced by PDT, which may be a tumor antigen-specific process coordinated by the innate immune system.…”

“…In addition, PDT activates the immune system and induces an inflammatory and immune response against tumor cells . After illumination, local edema was observed in the irradiation site of mice in the LS-HB PDT experimental group (Figure A).…”

Overexpression of Rhodopsin or Its Mutants Leads to Energy Metabolism Dysfunction in 661w Cells

“…As described before, 14 cell apoptosis and necrosis were analyzed by flow cytometry (Beckman Coulter, Brea, CA, USA) with an Annexin-VFITC/PI apoptosis detection kit (556547; BD Biosciences, San Jose, CA, USA). Cellular calcium levels, mitochondrial mass, mitochondrial reactive oxygen species (ROS), and calcium levels were detected by measuring the mean fluorescence intensity (MFI) with flow cytometry after loading cells with eBioscience Calcium Sensor Dye eFluor 514 (0.5 µM, 65-0859-70; Thermo Fisher Scientific, Waltham, MA, USA), MitoTracker Green FM (0.1 µM, M7514; Thermo Fisher Scientific), MitoSOX (0.5 µM, M36008; Thermo Fisher Scientific), and Rhod-2 AM cell permeant (0.5 µM, R1245MP; Thermo Fisher Scientific), respectively, for 30 minutes.…”