Suppressed Retinal Degeneration in Aged Wild Type and APPswe-PS1ΔE9 Mice by Bone Marrow TransplantationReportar como inadecuado

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Alzheimer-s disease AD is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides Aβ in brain and retina. Because bone marrow transplantation BMT results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe-PS1ΔE9 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 Aβ 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. Aβ 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.

Autor: Yue Yang, Christine Shiao, Jake Frederick Hemingway, Nikolas L. Jorstad, Bryan Richard Shalloway, Rubens Chang, C. Dirk Keene



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