STAT3 combined with Y27632 to treat glaucoma by promoting axon growth of Müller differentiated retina ganglion cells

Abstract

Abstract Müller differentiated RGCs have potential therapeutic value for glaucoma. However, axonal regeneration of differentiated RGCs has been a difficult problem. Retinal stem cells were differenticated from rat retinal Müller cells. The stem cells were randomly divided into five groups (control group, AAV-STAT3 group, shSTAT3 group, Y27632 group and AAV-STAT3 + Y27632 group). Stem cells in different groups were injected into rat model of glaucoma. The length of axon regeneration in STAT3 combined with Y27632 group was significantly longer than that in other experimental groups. The AAV-STAT3 transfected RGCs treated with Y27632 significantly increased the mRNA levels of Esrrb, Prdm14, Sox2, and Rex1, while decreasing the mRNA levels of Nestin, Eomes, Mixl1, and Gata4. Meanwhile, Socs3, Pten, Klf9, and Mdm4 were significantly lowered, while Dclk2, Armcx1, C-MYC, and Nrn1 were elevated. After injecting differentiated RGCs into the glaucoma model rat eyes, the axon length, RGC layer thickness and the electrophysiology were superior to the glaucoma model group. These findings suggested that STAT3 combined with Y27632 can significantly improve the axonal growth level of Müller differentiated RGCs, and reveal the potential mechanism to induce pluripotency of RGCs.