Young bone marrow Sca-1 cells protect aged retina from ischaemia-reperfusion injury through activation of FGF2.

Retinal ganglion cell apoptosis and optic nerve degeneration are prevalent in aged patients, which may be related to the decrease in bone marrow (BM) stem cell number/function because of the possible cross-talk between the two organs. This pathological process is accelerated by retinal ischaemia-reperfusion (I/R) injury. This study investigated whether young BM stem cells can regenerate and repair the aged retina after acute I/R injury. Young BM stem cell antigen 1 positive (Sca-1(+)) or Sca-1(-) cells were transplanted into lethally irradiated aged recipient mice to generate Sca-1(+) and Sca-1(-) chimaeras, respectively. The animals were housed for 3 months to allow the young Sca-1 cells to repopulate in the BM of aged mice. Retinal I/R was then induced by elevation of intraocular pressure. Better preservation of visual function was found in Sca-1(+) than Sca-1(-) chimaeras 7 days after injury. More Sca-1(+) cells homed to the retina than Sca-1(-) cells and more cells differentiated into glial and microglial cells in the Sca-1(+) chimaeras. After injury, Sca-1(+) cells in the retina reduced host cellular apoptosis, which was associated with higher expression of fibroblast growth factor 2 (FGF2) in the Sca-1(+) chimaeras. Young Sca-1(+) cells repopulated the stem cells in the aged retina and diminished cellular apoptosis after acute I/R injury through FGF2 and Akt signalling pathways.