Dose-Dependent Effects of Endothelin-1 on Retinal and Optic Nerve Morphology in Sprague Dawley Rats

ET1 induced retinal and optic nerve injury is widely used as an experimental model to study unexplained pathophysiology and therapeutic targets involved in several ophthalmic diseases such as glaucoma and diabetic retinopathy. Although a dose-dependent effect of ET1 on retinal vascular tone and retinal blood flow has been studied, the dose-dependent effects of ET1 on retinal and optic nerve morphology remain unexplored. Current study, therefore investigated the dose-dependent effects of ET1 on retinal and optic nerve morphology. Sprague Dawley rats were injected with ET1 in the dose range of 0.025-2.5 nM, intravitreally. Seven days post-injection, eyes were enucleated and retinal sections were examined for morphological changes using H&E staining and extent of retinal cell apoptosis was determined using TUNEL staining. Optic nerve morphology was studied using toluidine blue staining. It was observed that ET1 induces significant changes in retinal and optic nerve morphology at 0.25 and 2.5 nM doses but not at 0.025 nM. The outcomes of in vivo studies using different doses of ET1, therefore, may not be comparable. Furthermore, while designing experimental studies using ET1 induced retinal ischemia, it is important to carefully make the dose selection based on the study objectives.