Abstract
PURPOSE: This study aimed to evaluate the efficacy of photoimmunotherapy (PIT) targeting VEGFR2 for the treatment of neovascular AMD and to investigate its potential as a novel therapeutic strategy. METHODS: DC101-IR700, a conjugate of the anti-mouse VEGFR2 monoclonal antibody DC101 and the photosensitizer IR700, was investigated both in vitro and in vivo. VEGFR2 expression in endothelial cells was confirmed via qPCR and immunocytochemistry. Laser-induced choroidal neovascularization (CNV) was established in C57BL/6J mice. Localization of DC101-IR700 within CNV lesions was assessed by immunofluorescence. After PIT was performed using either a 690 nm near-infrared manual laser or a slit lamp laser, CNV volumes were quantified through confocal microscopy. Cell viability post PIT was measured using MTT assay and cell death in CNV lesions was evaluated using TUNEL staining. RESULTS: DC101-IR700 localized specifically to VEGFR2-positive cells in CNV lesions, and PIT induced significant VEGFR2-dependent cytotoxicity in vitro. In vivo, both PIT and directional PIT using slit lamp laser significantly reduced CNV volumes compared with controls. TUNEL staining confirmed VEGFR2-specific cell death in treated CNV lesions. Directional PIT achieved similar efficacy to PIT, demonstrating its potential as a clinically viable alternative. CONCLUSIONS: PIT targeting VEGFR2 selectively induced cell death in pathological neovascular tissues, significantly reducing CNV volume in an AMD model. These findings suggest that VEGFR2-specific PIT represents a promising and targeted approach for treating neovascular AMD, offering advantages over conventional anti-VEGF therapies by potentially decreasing treatment frequency and improving efficacy.