Model of Endothelin-1–Induced Chronic Optic Neuropathy in Rat

Abstract

ET-1 led to a mean reduction in optic nerve blood flow of 68%. There were no significant differences in RGC survival among the four ET-1 doses used in this study. Pooled across all ET-1 doses, RGC survival decreased incrementally at 21, 42, and 84 days (P < 0.001; mean +/- SD, 0.77 +/- 0.25, 0.60 +/- 0.27, and 0.50 +/- 0.26, respectively) and was statistically significantly lower at each time point than in the BSS-treated animals. The axon survival data also showed a similar time-dependent loss. Only one of 21 animals showed significantly increased disc cupping, and there was no relationship between RGC survival and change in cupping. CONCLUSIONS. Chronic administration of ET-1 to the rat optic nerve results in a time-dependent loss of RGCs and their axons without apparent change in optic disc topography.

Differential Gene Expression in Glaucoma

“…They are potent vasoconstrictors and have been found to be elevated in the aqueous humor of glaucoma patients (Noske et al 1997;Tezel et al 1997). Intraocular administration of endothelin 1 leads to acute blockage of axonal transport Wang et al 2008b), optic neuropathy, and ganglion cell loss (Chauhan et al 2004;Sasaoka et al 2006). It was recently shown that endothelin 2, which binds to the same receptors as endothelin 1, also causes ganglion cell loss and optic nerve damage (Howell et al 2011).…”

Ischemic model of optic nerve injury

“…The model of chronic optic nerve ischemia continuously delivers ET-1 to the perineural region of the optic nerve in the retrobulbar space and has been described in rabbits, 91 rats, 119 and nonhuman primates. 120 The arterial supply of the anterior optic nerve in the rabbit is anatomically similar to the primate eye and demonstrates a dose-dependent vasoconstriction with chronic, local application of ET-1.…”

Neurovascular Interactions in the Retina: Physiological and Pathological Roles

“…Plasma and aqueous humor concentrations of ET-1 have been shown to be elevated in patients with ocular hypertension as well as in the corresponding animal models (49 -51). Chronic local administration of ET-1 to the optic nerve head reduces optic nerve head blood flow and is associated with a loss of retinal ganglion cells (52). In addition to these vascular effects, ET-1 is implicated in pathological changes in the retina such as neuronal cell apoptosis, microvascular basement membrane thickening, and gliosis (53).…”