Anti-Glaucoma Effects of Timolol and Bimatoprost in Novel Ocular Hypertension Model in Rats

Yulan Lu, Zhong Chen, Jie He, Lan Li, Rong Chen and Jili Chen

Background and Objective: Glaucoma is a chronic, progressive condition marked by irreversible optic neuropathy. Thus, lowering IOP is a critical goal of glaucoma treatment. To determine the effects of 0.03% bimatoprost and 0.5% timolol or their combination on intraocular pressure reduction, anti-apoptotic molecule expression and neuroretinal changes in a rat model of chronic ocular hypertension. Materials and Methods: This study investigated the hypotensive effects of 0.5% timolol, 0.3% bimatoprost and their fixed-dose combination in chronic glaucoma rats induced by conjunctival fibroblasts intracamerally into the anterior chamber for 16 days. Histological analysis, retinal ganglionic cells RGCs count using BRN3A and TUNEL assay for apoptosis was carried out. The levels of glutamate and glutathione (GSH) in the vitreous and aqueous humour were also determined. Results: The cell-injected eyes were treated with 0.03% bimatoprost and 0.5% timolol or their fixed-dose combination that showed a significant reduction in intraocular pressure (IOP) relative to the control group. On the treatment with timolol, bimatoprost and their fixed combination eye drop raised glutathione levels by 38.3, 34.4 and 89.2%, whereas glutamate levels were reduced by 12.2, 14.1 and 35.9%, respectively. The treatment considerably reduced the RGCs count with improved morphological alterations in ciliary bodies, head cupping of optic nerves, thinning of retinae and apoptotic signalling as compared to cell-injected model rats. Conclusion: The study findings showed that the combination of bimatoprost (0.03%) and timolol (0.5%) offers neuroprotective effects for the treatment of chronic rat model of glaucoma induced by injection of conjunctival fibroblasts intracamerally but the underlying mechanism of neuroprotection needs further study in other chronic glaucoma models.

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