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

年轻骨髓中的Sca-1细胞通过激活FGF2来保护老年视网膜免受缺血再灌注损伤。

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Abstract

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.

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