Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases

Abstract

The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases. On intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina. In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells. The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases.