Neuro-protection of retinal stem cells transplantation combined with copolymer-1 immunization in a rat model of glaucoma

Abstract

Glaucoma is a chronic, neurodegenerative disease that often leads to blindness. A common treatment is to reduce intraocular pressure (IOP), but this approach does not halt visual loss caused by the death of retinal ganglion cells (RGCs). Therefore, there is an important need for therapies that protect against RGCs degeneration. The present study in a rat glaucoma model aimed to determine whether retinal stem cells (RSCs) transplantation plus vaccination with a glatiramer acetate copolymer-1 (COP-1) could confer neuroprotection. Rats were immunized with COP-1 on the same day as IOP induction by argon laser photocoagulation of the episcleral veins and limbal plexus. RSCs were cultured and transplanted intravitreally 1week after laser treatment. The expression of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor I (IGF-I) was detected by immunohistochemical staining, RT-PCR, and western blotting. RGCs survival was assessed by TUNEL staining and RGCs counting. We found that the expression of BDNF and IGF-I in the RSCs/COP-1 group was significantly higher than in other groups (P<0.05). In addition, the number of the apoptotic RGCs in the RSCs/COP-1 group was notably lower than in other groups (P<0.05), and the number of RGCs in the RSCs/COP-1 group was higher than in other groups (P<0.05). We conclude, therefore, that the combined effects between RSCs transplantation and COP-1 immunization protect RGCs from apoptosis in our rat model of glaucoma. The increase in levels of secreted BDNF and IGF-I may be one of the mechanisms underlying the neuro-protection of RGCs.