Effect of olfactory ensheathing glia clone TEG3 on neuroprotection, microglial activation and gene expression profile of allotransplanted retina with and without immunosuppression

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AbstractPurpose: Olfactory ensheathing glia (OEG) is a macroglia from the embryonic ectoderm, with unique functions in guiding sensory axons from the olfactory mucosa (PNS) to the olfactory bulb (CNS). These properties, together with their high secretion of trophic factors, have made its use a field of study in axonal regeneration. However, their in vivo administration in the retina had never been tested, so we set out to evaluate their actions in the retina without injury and after an optic nerve crush (ONC) model. In addition, to simulate the clinical conditions of an allogeneic cell transplant, we evaluated how their properties were altered when combined with immunosuppressive treatment.Methods: Wistar TEG3‐GFP+ cells were administered into the vitreous of SD female rats. Experimental groups: transplantation in intact retinas, in retinas just after ONC, and both with systemic immunosuppression. In some animals of each group, the retina was dissected for anatomical analysis and the total number of retinal ganglion cells (RGCs) was counted and the morphological activation of microglia was studied. The retinas of the remaining animals were dissected fresh for the study of gene expression by real‐time quantitative PCR. Animals injected with vehicles after ONC and intact animals without injury were used as controls. n = 3–8 animals/group/analysis.Results: TEG3 neuroprotected RGCs after ONC at 7 days (18% more survival compared to vehicle group p < 0.05) but caused a large activation of microglia cells coupled with a 33% (p < 0.01) reduction of RGCs 21 after transplantation in intact retinas. Immunosuppression had no effect on neuroprotective properties but did recover some of the death observed at 21 days in intact retinas (up to a 17%, p < 0,05). Immunosuppression reduced the expression of pro‐inflammatory molecules (Tnf, Il6), macrogliosis markers (Gfap) and macrophage markers (Ptprc) in favour of anti‐inflammatory ones (Il10). However, markers of pyroptotic cell death (Casp4, Gsdmd) did not change after treatment, which would explain the elevated microglial activation and death observed at 21 days in intact and grafted retinas.Conclusions: TEG3 has a dual effect neurotoxic and neuroprotective in retina.