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Fig. 5. (A) EPO protects from age-dependent death of RGCs in DBA/2J mice. (A) EPO profoundly protected RGC layer cells from glaucoma in DBA/2J mice. These results are convincing as the authors successfully analyzed at least 24 eyes (from 12 mice) in each treatment group (172 eyes total, personal communication, Ng). EPO was administered intraperitoneally three times per week for 2, 4, or 6 months. Compared with untreated control mice, which lost W70% of total RGCs, DBA/2J mice treated with different concentrations of EPO show no significant RGC loss up to 12 months of age. (B) Localization of EPOR expression in the retina of DBA/2J mice immunostained with antibodies to EPOR; NeuN, a marker for neurons; and GFAP, a marker for astrocytes. Top: In the DBA/2J mice, EPOR expression was colocalized with most of the NeuN-positive cells in the RGC layer (yellow, arrows). Bottom: most of the EPOR-positive (green, arrowheads) cells are located below the GFAP-positive (red) astrocytes in the RGC layer, and a few astrocytes have detectable EPOR expression (yellow, arrow). Scale bars, 100 mm; insets: 10 mm. Adapted with permission from Zhong et al. (2007).

combination with a syngeneic bone marrow transplant (Anderson et al., 2005). This treatment profoundly protects from glaucoma in the vast majority of treated animals but does not alter IOP. Importantly, this treatment is given to young mice and remains protective until old age. This protection appears to extend to humans because the incidence of glaucoma is reported to be lower in populations exposed to radiation (such as atomic bomb survivors, Yamada et al., 2004; and see Anderson et al., 2005). At this time, the mechanism(s) of neuroprotection are not known, and in its current form, the treatment is not directly transferable to humans. Further studies are needed to understand the process(es) involved in this radiation-induced neuroprotection, but there is great potential for the development of powerful new neuroprotective therapies for those at risk of glaucomatous visual loss.

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