The anti-apoptotic and neuro-protective effects of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) on acute optic nerve injury is transient.
Progressive death of retinal ganglion cells (RGCs) is a major cause of irreversible visual impairment after optic nerve injury. Clinically, there are still no effective treatments for recovering the visual function at present. The probable approaches to maintain the vision and RGCs function involve in preventing RGCs from death and/or promoting the regeneration of damaged RGCs. Previous studies have shown that mesenchymal stem cells (MSCs) take neuroprotective effects on ischemia-induced cortical and spinal cord injury, however, whether MSCs have a beneficial effect on the optical nerve injury is not clearly determined. In present study, we transplanted MSCs derived from human umbilical cord blood (hUCB-MSCs) into the vitreous cavity of adult rats and investigated the probable capacity of anti-apoptosis and pro-neuroprotective effects on RGCs. RGCs were retrogradely traced by fluorescent gold particles (FG); cellular apoptosis was investigated by caspase-3 immunohistochemistry and terminal dUTP nick end labeling (TUNEL) staining. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of the retina. Growth associated protein 43 (GAP-43), an established marker for axonal regeneration, was used to visualize the regenerative process over time. Expression of P2X7 receptors (P2X7R), which are responsible for inflammatory and immune responses, was also monitored in our experiments. We found that the hUCB-MSC transplantation significantly decreased cellular apoptosis and promoted the survival of RGCs in early phase. However, this protection was transient and the RGCs could not be protected from death in the end. Consistent with apoptosis detection, P2X7R was also significantly decreased in hUCB-MSC transplanted rats in the early time but without obvious difference to the rats from control group in the end. Thus, our results imply that hUCB-MSCs take anti-apoptotic, pro-neuroregenerative and anti-inflammatory effects in the early time for acute optic nerve injury in adult rats but could not prevent RGCs from death eventually.
Department of Ophthalmology of Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Meilan
M
Chen
Zhenghua
Z
Xiang
Jiping
J
Cai
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D036101:Cord Blood Stem Cell Transplantation; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology*
D019922:GAP-43 Protein; D058486:Receptors, Purinergic P2X7
Axonal regeneration; Fluorogold retrograde tracing; GAP43; Hucb-MSCs; Optic nerve injury; P2X7R