Morphological Changes in the Optic Nerve Induced by Experimental Elevation in Intraocular Pressure and Effect of Latanoprost

The aim of this study was to evaluate the effects of chronic elevated intraocular pressure (IOP) on the myelinated region of the optic nerve and the response to treatment with the ocular hypotensive drug latanoprost. Ocular hypertension was induced unilaterally in Wistar rats by episcleral vein cauterization. After 3 months, the optic nerves were removed and processed for microscopic examination. Effects of elevated IOP and latanoprost treatment were analyzed by light and electron microscopy. Quantitative parameters were obtained from electron micrographs of the cross-sectioned optic nerves. Elevated IOP caused axonal degeneration and astrocyte reaction, with hypertrophic changes in morphology. The mean axonal density decreased significantly (23%, P<0.005) and degenerating profiles increased compared with the control eyes (57.77±2.96 and 6.06±0.36, respectively) (P=0.000). After topical treatment with latanoprost, axon density rose 19% compared with the untreated group and the mean number of degenerative profiles was significantly less (19.00±0.85) (P=0.000). The astrocyte reaction in the treated group continued to show marked hypertrophy and signs of proliferation. These results indicate a correlation between chronic elevated IOP, loss of axons and astrocyte reaction, probably induced by demyelination. We suggest that the hypotensive effects of latanoprost are associated with neuroprotective activity in axons in the myelinated optic nerve that may be mediated in part by the reaction of the astrocytes. Central Bringing Excellence in Open Access   Vidal et al. (2015) Email: JSM Ophthalmol 3(3): 1037 (2015) 2/7 as reactive gliosis in the retina [16]. Conventional treatment of glaucoma has been aimed at controlling the IOP through administration of hypotensive agents [19,20]. The prostaglandin F2α analog latanoprost is one of the most important drugs used clinically in patients with glaucoma [21-23]. Latanoprost exerts its hypotensive effect by increasing the uveoscleral flow, though its exact mechanism of action is unknown [24,25]. It increases the blood flow in the ONH [26] and has neuro-protective effects that may contribute to its efficacy in glaucoma therapy [27]. In previous studies, we found that the animals treated with this drug had the lowest percentage loss of RGC [28] and the lowest retinal glial reactivity [16] as compared with the other hypotensive drugs used. We also suggested that the hypotensive effect of latanoprost is associated with its vascular action on ONH capillaries [29]. The purpose of this study was to determine whether a chronic rise in IOP in the rat eye induces optic nerve axon loss and gliosis. After evaluating quantitative parameters, we undertook a comparative examination of axons and astrocytes in the myelinated region of the ON of rats treated topically for 3 months with latanoprost to study the neuroprotective effect of this hypotensive drug. MATERIALS AND METHODS