Intravitreal Application of Mesenchymal Stem Cell By-Products Does Not Ameliorate Experimental Autoimmune Uveitis

The study aimed to evaluate the therapeutic effects of mesenchymal stem cells and their by-products, including conditioned medium, extract and exosomes, on intraocular inflammation in experimental autoimmune uveitis. Uveitis was induced in the C57BL/6J mouse strain by administration of interphotoreceptor retinoid-binding protein, complete Freund’s adjuvant and pertussis toxin. Mesenchymal stem cell-derived products (conditioned medium, extract and exosomes) were prepared and administered intravitreally at varying time points post-induction, primarily on day 14. Retinal inflammatory changes were monitored using fundus imaging, flow cytometry and RT-PCR analysis to evaluate clinical manifestation of inflammation, immune cell infiltration and gene expression of inflammatory markers. In vivo, administration of mesenchymal stem cell by-products did not ameliorate experimental autoimmune uveitis. On the contrary, treated eyes exhibited exacerbated inflammation, including increased immune cell infiltration and up-regulated pro-inflammatory gene expression (e.g., Gfap , Iba1 , Il1b and Il17 ). In vitro studies suggested a trend towards anti-inflammatory effects of the conditioned medium, but these findings were not replicated in vivo . Control experiments on healthy eyes indicated that intravitreal trauma alone significantly contributed to inflammatory responses, irrespective of the substance injected. Intravitreal application of mesenchymal stem cell by-products did not demonstrate therapeutic benefits in the experimental autoimmune uveitis model and instead promoted inflammation. The results highlight the impact of administration-induced trauma and suggest that alternative delivery methods, such as systemic administration, may be more effective for mesenchymal stem cell-based therapies.