J Clin Invest.
Restoring EDN2 to radiation-treated eyes induces a pattern of damage that is characteristic of glaucoma.
EDN2, injected into the vitreous of radiation-treated eyes, caused glaucoma-like RGC damage that was not observed in control eyes. (A) Most radiation-treated, EDN2-injected DBA/2J eyes had moderate and severe optic nerve damage. This was not the case for EDN2-injected untreated D2-Gp or radiation-treated D2-Gp eyes or eyes injected with vehicle (1× PBS, n > 15 each group, all age matched). D2-Gp mice do not develop high IOP and glaucoma, and so EDN2 induces the most damage in eyes that have high IOP and possibly other stresses that are not sufficient by themselves to induce glaucoma. Thus, EDN2 is a damaging factor that conspires with other stresses to induce glaucoma but is diminished in radiation-treated eyes. (B) Axon counts demonstrated a significant increase in axon loss in radiation-treated, EDN2-injected DBA/2J eyes compared with that in D2-Gpnmb+ controls (*P < 0.0001). (C) Radiation-treated, EDN2-injected DBA/2J eyes had fan-shaped patterns of RGC loss, with discrete borders in the retina and regional axon loss in the ONHs (key characteristics of glaucoma). NFL, Anti-neurofilament antibody. Fan-shaped patterns were not observed in D2-Gpnmb+ or radiation-treated D2-Gpnmb+ controls. V, vessel. Scale bars: 100 μm (retina); 50 μm (ONH).