Neuroprotective effects of bone marrow Sca-1⁺ cells against age-related retinal degeneration in OPTN E50K mice

Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1⁺ and Sca-1^- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1⁺ and Sca-1^- chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1⁺ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1⁺ cells from young healthy mice had greater paracrine trophic effects than Sca-1^- cells and Sca-1⁺ cells from young OPTN E50K mice. In addition, Sca-1⁺ chimaeras demonstrated better visual functions than Sca-1^- chimaeras and untreated OPTN E50K mice. More Sca-1⁺ cells than Sca-1^- cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1⁺ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.