A rat model of glaucoma induced by episcleral vein ligation

To establish a reliable animal model of glaucoma, we examined if episcleral vein ligation in rat eyes can induce intraocular pressure (IOP) elevation and concomitant characteristic morphological features of glaucoma. IOP elevation was detected on the next day (30.1+/-4.4 mmHg: operated eyes; 21.0+/-1.8 mmHg: control eyes) and persisted at least 7 months after the procedure (24.5+/-2.3 mmHg: operated eyes; 19.7+/-1.9 mmHg: control eyes). These results suggest that episcleral vein ligation can induce very mild IOP elevation immediately after the operation, which can last over several months. Furthermore, it appears there was little variability in the patterns of IOP elevation among the individual eyes treated with episcleral vein ligation. Morphological changes were detected selectively in the retinal ganglion cell (RGC) layer and optic disc excavation was evident in the late stage of chronic IOP elevation. RGCs were selectively lost by apoptotic death. The number of RGCs was reduced by 18% at 12 weeks and eventually by 35% at 8 months postoperatively. Müller cells downregulated the expression of p27Kip1 and appeared to be partially in a reactive state even at the advanced stages of glaucoma. The expression of basic fibroblast growth factor and ciliary neurotrophic factor, which are neurotrophic factors implicated in the control of cell survivals and neuroprotection, significantly declined at the advanced stages. Taken altogether, these observations indicate that the episcleral vein ligation model based on the simple ligation procedure reproducibly provides a reliable glaucoma model and contributes to give insights into the underlying molecular and cellular bases of human glaucoma and to devise the new medication upon the disease.