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.
Highlights
Aging diminishes the functional capacity of stem cells and reduces the ability of the aged organism to repair tissue following injury.[1]
We found that bone marrow (BM) chimaerism established with young Sca‐1+ cells was associated with better restoration of retina progenitors and improved healing of the aged retina after injury
The mRNA levels of fibroblast growth factor 2 (FGF2), insulin‐like growth factor 1 (IGF‐1), and ciliary neurotrophic factor (CNTF) were significantly higher in the Sca‐1+ than Sca‐1− chimaeras at 3 days post‐I/R injury (Figure 5A‐C), though there was no significant difference in the mRNA level of nerve growth factor (NGF), FGF1, stem cell factor (SCF), and neuron‐derived neurotrophic factor (NDNF) mRNA between the two groups (Figure 5D‐G) at 3 days
Summary
Aging diminishes the functional capacity of stem cells and reduces the ability of the aged organism to repair tissue following injury.[1]. A sight‐threatening disorder associated with death of retinal ganglion cells (RGCs) and degeneration of optic nerve fibres, affects millions of people worldwide and advanced age is widely recognised as one of the major risk factors for many of the leading causes of vision loss, including glaucoma.[2,3]. The incidence of glaucoma increases exponentially with age.[4,5]. Retinal ischaemia‐reperfusion (I/R) is a pathophysiological process contributing to the cellular damage in glaucoma. Damage to any type of retinal neuron initiates the loss of vision and therapeutic modalities that can reverse these degenerative processes are required to prevent or reverse vision loss. Aged and diseased tissues provide an unfavourable microenvironment for regeneration.[6–8]. Aged and diseased tissues provide an unfavourable microenvironment for regeneration.[6–8] an intervention to rejuvenate the aged retina may be an important and innovative treatment strategy.[1,9]
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