Celecoxib-loaded mesenchymal stem cell-derived exosomes ameliorate laser-induced choroidal neovascularization in a rabbit model

Neovascular age-related macular degeneration (nAMD), cause of central vision blindness, is associated with choroidal neovascularization (CNV). The objective of this research was to assess the treatment capabilities of Celecoxib-loaded exosomes, and directly compare their efficacy with three other approaches, free Celecoxib, pure exosomes, and Bevacizumab, in a laser-induced CNV rabbit model. Human umbilical cord mesenchymal stem cells (hUC-MSCs) derived exosomes were isolated by ultracentrifugation and identified means of dynamic light scattering, field emission scanning electron microscopy, and flow cytometry. Celecoxib was loaded into exosomes through passive incubation. Eighteen rabbits were divided into six groups: a healthy control group, an untreated CNV group, and four treatment groups. CNV was induced by thermal laser photocoagulation. Therapeutic effects were examined via fluorescein angiography (FA), optical coherence tomography (OCT), and histopathological analysis. The exosomes showed successful structural and surface marker profiles, and Celecoxib was effectively loaded with an efficiency of 18.08 ± 0.21 %. All treatment groups exhibited significant reductions (p < 0.0001) in CNV area and vascular leakage relative to the untreated control. The group receiving Celecoxib-loaded exosome showed the most substantial improvement in imaging outcomes, reducing CNV thickness by 60.43 % and fluorescein leakage by 75.95 % in OCT and FA analyses, respectively. Histopathological evaluation further confirmed therapeutic efficacy, showing a 72.79 % reduction in CNV thickness. Delivering Celecoxib via exosomes markedly enhanced its therapeutic performance in CNV. This combined strategy leverages the anti-inflammatory and anti-angiogenic capabilities of Celecoxib with the regenerative capacity and targeted delivery advantages of exosomes, offering a promising direction for future treatments of nAMD.