Effect of human umbilical cord blood mesenchymal stem cells administered by intravenous or intravitreal routes on cryo-induced retinal injury.

Traumatic optic neuropathy is an important cause of severe vision loss. So, many attempts were performed to transplant stem cells systemically or locally to regenerate the injured retina. In this study, we investigated the effect of human umbilical cord blood mesenchymal stem cells (hUBMSCs) on histological structure, apoptotic, antiapoptotic, oxidant and antioxidant markers in an experimental model of cryo-induced retinal damage in mice. Forty-eight mice were included with 4 major groups; group I contained 18 mice as controls. The others included 30 mice exposed to cryo-induced retinal injury and were subdivided into three equal groups: group II received no treatment after injury. Group III was intravenously injected with hUCBMSCs after injury and group IV received an intravitreal injection with hUCBMSCs into both eyes. Retinal tissues were used for histopathological, immunological and gene expression studies. Real time-PCR was performed to assess B-cell lymphoma 2 (bcl2), Bcl2-associated X protein (bax), heme oxygenase-1 (hmox-1) and thioredoxin-2 (tnx-2) expression and to assess the differentiation of the stem cells into the retinal tissue. Immunohistochemical analysis was performed to assess caspase-3, 3-nitrotyrosine (3-NT) and basic fibroblast growth factor (bFGF). Disturbed retinal structure was seen in cryo-injured mice while hUCBMSCs treated groups showed nearly normal structure. By real time-PCR, significantly reduced mRNA expressions of Bax and notably enhanced mRNA expression of Bcl-2, hmox-1 and txn-2 were demonstrated in retinal injured mice with hUCBMSCs treatment compared to those without. In addition, immunohistochemical analysis confirmed downregulation of 3-NT and caspase-3 and upregulation of bFGF after hUCBMSCs injection in injured retina. Furthermore, there was no differentiation of transplanted stem cells into the retinal tissue. In conclusions, hUCBMSCs could improve the morphological retinal structure in cryo-induced retinal damage model by modulation of the oxidant-apoptotic status and by increased the expression of bFGF.