| First Author | Yang Y | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 6 | Pages | e64246 |
| PubMed ID | 23750207 | Mgi Jnum | J:204261 |
| Mgi Id | MGI:5529898 | Doi | 10.1371/journal.pone.0064246 |
| Citation | Yang Y, et al. (2013) Suppressed retinal degeneration in aged wild type and APPswe/PS1DeltaE9 mice by bone marrow transplantation. PLoS One 8(6):e64246 |
| abstractText | Alzheimer's disease (AD) is an age-related condition characterized by accumulation of neurotoxic amyloid beta peptides (Abeta) in brain and retina. Because bone marrow transplantation (BMT) results in decreased cerebral Abeta in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Abeta. To test this, we performed BMT in APPswe/PS1DeltaE9 double transgenic mice using green fluorescent protein expressing wild type (wt) mice as marrow donors. We first examined retinas from control, non-transplanted, aged AD mice and found a two-fold increase in microglia compared with wt mice, prominent inner retinal Abeta and paired helical filament-tau, and decreased retinal ganglion cell layer neurons. BMT resulted in near complete replacement of host retinal microglia with BMT-derived cells and normalized total AD retinal microglia to non-transplanted wt levels. Abeta and paired helical filament-tau were reduced (61.0% and 44.1% respectively) in BMT-recipient AD mice, which had 20.8% more retinal ganglion cell layer neurons than non-transplanted AD controls. Interestingly, aged wt BMT recipients also had significantly more neurons (25.4%) compared with non-transplanted aged wt controls. Quantitation of retinal ganglion cell layer neurons in young mice confirmed age-related retinal degeneration was mitigated by BMT. We found increased MHC class II expression in BMT-derived microglia and decreased oxidative damage in retinal ganglion cell layer neurons. Thus, BMT is neuroprotective in age-related as well as AD-related retinal degeneration, and may be a result of alterations in innate immune function and oxidative stress in BMT recipient mice. |
