Suppressed Retinal Degeneration in Aged Wild Type and APP swe/PS1ΔE9 Mice by Bone Marrow Transplantation

Alzheimer's disease (AD) is an age-related condition characterized by accumulation of neurotoxic amyloid beta peptides (A beta) in brain and retina. Because bone marrow transplantation (BMT) results in decreased cerebral A beta in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal A beta. To test this, we performed BMT in APPswe/PS1 Delta E9 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 A beta 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. A beta 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.