Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes.

PURPOSE: To assess the efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) to promote the healing of large and refractory macular holes (MHs). METHODS: Seven patients (age 51-75 years old) with large and long-standing idiopathic MHs underwent vitrectomy, internal limiting membrane peeling, MSC (two patients) or MSC-Exo (five patients) intravitreal injection, and heavy silicon oil, air, 20% SF6, or 14% C3F8 tamponade. The MSCs were isolated from human umbilical cord tissue, and MSC-Exos were isolated from the supernatants of cultured MSCs using sequential ultracentrifugation. RESULTS: Five eyes underwent pars plana vitrectomy (PPV) only, while two underwent PPV combined with cataract surgery. Six MHs were closed, while one remained in a flat-open state. The best-corrected visual acuity (BCVA) was improved in five patients with MH closure and remained unchanged in one patient with MH closure who had a 4-year history of MH. A fibrotic membrane was observed on the surface of the retina in one patient who underwent MSC therapy. One patient who received a higher dose of MSC-Exos exhibited an inflammatory reaction. CONCLUSIONS: MSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving the visual outcomes after surgery for refractory MHs.

Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration.

Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity.