Exosomes derived from IL4-treated microglia alleviate retinal ganglion cell loss and alleviate retinal damage in diabetic retinal neuropathy

In the progression of diabetic retinal neuropathy, the loss of the retinal ganglion cells (RGCs) is an important event, which involves multiple pathological changes especially the inflammation. IL4-treated microglia are activated during the repair of CNS injury. We hypothesize that their role in diabetic retinopathy may also be significant.However, their effect and the mechanism behind diabetic retinal neuropathy are unknown. Here, we investigated the protective role of IL4-treated microglia derived exosome (IL4-Exos) in diabetic retinal neuropathy. Firstly, we provided evidence that IL4-treated microglia participated in the process of both human and rodent diabetic retinal neurodegeneration. In the Streptozotocin (STZ) induced diabetes mice model, intravitreal injection of IL4-Exos prevented RGC loss by changing inflammatory factors, thus preserving the ganglion cell complex thickness and visual capabilities. In the in vivo optic nerve crush (ONC) model, IL4-Exos preserved RGC axons and central retinal projections following optic nerve injury. Our exosomal miRNA sequencing indicated that IL4-Exos contained high levels of miR-26a-5p, which may target the PTEN mRNA and activate the PI3K/AKT signalling pathway. These findings indicate that IL4-Exos exert neuroprotective effects and axonal integrity effects of RGCs through the miR-26a-5p/PTEN/PI3K/AKT axis.