Abstract
Diabetic retinopathy (DR) is a highly specific condition affecting the microvasculature that is the leading cause of visual impairment in working-age people in developed countries. The ability of intravitreal administration of mesenchymal stem cells (MSCs) to repair the retinal vasculature and neurons of the inner retina in DR has been explored. It was recently revealed that exosomes are primarily responsible for the therapeutic effects of MSCs; therefore, intravitreal injection of these vesicles appears to be a better option for treatment of retinal injury, and there is evidence that hypoxic conditions can promote exosome release from MSCs. Here we investigated the effect of intravitreal injection of hypoxia-induced human umbilical cord mesenchymal stem cell exosomes (hypo-hucMSC-Exs) on the retinal microvasculature in rats with DR. We also assessed whether hypo-hucMSC-Exs exhibited greater effects on DR than exosomes from human umbilical cord mesenchymal stem cells not exposed to hypoxia (hucMSC-Exs). Exosomes were isolated from MSCs cultured under normoxic and hypoxic culture conditions. Transmission electron microscope, nanoparticle tracking, and western blot analyses were applied to characterize hucMSC-Exs. Streptozotocin (STZ)-induced diabetic rats were used as a model for DR. Fundus fluorescein angiography (FFA) was conducted to evaluate retinal microvasculature changes in vivo at 4, 8, and 12 weeks following intravitreal injection of exosomes. No significant changes were observed in the control rats without DR receiving intravitreal phosphate-buffered saline (PBS) injection throughout the study. Control model rats receiving PBS injections developed DR characterized by retinal microvascular changes, including tortuous vessels, massive microaneurysms, and late leakage of fluorescein dye was, which were visualized using FFA. These changes were ameliorated in diabetic rats treated with hucMSC-Exs. Further, injection of hypo-hucMSC-Exs remarkably reduced the extent of microvasculature lesions compared with hucMSC-Exs. These findings suggest that intravitreal injection of hucMSC-Exs can prevent diabetes-induced microvasculature lesions and that hypo-hucMSC-Exs can enhance this effect and have potential for application in DR prevention and treatment.
[Corrigendum] Preliminary research on the effects and mechanisms of umbilical cord‑derived mesenchymal stem cells in streptozotocin‑induced diabetic retinopathy
