Human Umbilical Cord Blood-Derived CD133CD34 Cells Protect Retinal Endothelial Cells and Ganglion Cells in X-Irradiated Rats through Angioprotective and Neurotrophic Factors.

Radiation retinopathy (RR) is a common complication following radiation therapy of globe, head, and neck malignancies, and is characterized by microangiopathy, neuroretinopathy, and the irreversible loss of visual function. To date, there is no effective treatment for RR. Stem cells have been clinically used to treat retinal degeneration. CD133CD34 cells from human umbilical cord blood (-CD133CD34 cells), a subpopulation of hematopoietic stem cells, were applied to determine their protective efficacy on irradiated rat retinas. After X-ray irradiation on the retinas, rats were intravitreally injected with -CD133CD34 cells. Transplantation of -CD133CD34 cells prevented retinal dysfunction 2 weeks post-operation and lasted at least 8 weeks. CD133CD34 cells were distributed along the retinal vessel and migrated to the ganglion cell layer. Moreover, grafted CD133CD34 cells reduced the apoptosis of endothelial and ganglion cells in irradiated rats and increased the number of survived CD31 retinal endothelial cells and Brn3a ganglion cells at 2 and 4 weeks, respectively, post-operation. Co-culturing of CD133CD34 cells or supernatants with irradiated human retinal microvascular endothelial cells (hRECs) confirmed that CD133CD34 cells ameliorated hREC apoptosis caused by irradiation. Mechanistically, we found that angioprotective mediators and neurotrophic factors were secreted by CD133CD34 cells, which might attenuate irradiation-induced injury of retinal endothelial cells and ganglion cells. hUCB-CD133CD34 cell transplantation, as a novel treatment, protects retinal endothelial and ganglion cells of X-irradiated rat retinas, possibly through angioprotective and neurotrophic factors.