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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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC7363772 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Liu Yang Y   Zhu Min M   Gong Ruowen R   Wang Xin X   Li Lei L   Xu Gezhi G  

Frontiers in cell and developmental biology 20200709


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 i  ...[more]

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