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Partial Optic Nerve Transection in Rats: A Model Established with a New Operative Approach to Assess Secondary Degeneration of Retinal Ganglion Cells

Previous studies have shown that the secondary degeneration of retinal ganglion cells (RGCs) occurs commonly in glaucoma. Partial optic nerve transection ...

Central South University, Changsha, China

Transsynaptic degeneration has been implicated in patients with primary open angle glaucoma (POAG) and animal models of chronic intraocular hypertension. Whether the sustained intraocular pressure (IOP) elevation is necessary for the induction of transsynaptic changes in the brain remains unclear. The aim of this study is to characterize the effects of acute and transient intraocular hypertension on the visual pathway of rats. Acute intraocular hypertension was induced in the right eye by anterior chamber perfusion. At 1 day, 3 days, 1 week, 2 weeks and 4 weeks after the operation, neuronal degeneration and glial responses in the retina, dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) were assessed using Nissl staining and immunohistochemistry. TUNEL staining was also performed to detect the neuronal apoptosis in the brain. At the first day after the operation, no obvious neuronal changes were detected in the retina or the brain. At 3 days, 46% of the retinal ganglion cells (RGCs) were lost. Atrophy of the contralateral optic tract was also observed. Meanwhile, the cross-sectional area of neurons in the contralateral dLGN and SC was decreased, while cell density in the same regions was increased. Glial activation in the retina occurred much earlier than the RGC loss. Co-expression of glial fibrillary acid protein (GFAP) and glutamine synthetase (GS) was observed in the end-feet and processes of Müller cells at 1 day after the operation. GFAP immunoreactivity was remarkably increased in the contralateral dLGN and SC at 3 days. It also showed a good co-localization with GS. All of aforementioned changes gradually progressed and persisted for the whole observation period. No TUNEL-positive cells were detected in the dLGN and SC at any post-operative time point. Taken together, these results illustrate that acute and transient intraocular hypertension is able to induce early onset and long-lasting neurodegenerative changes and the accompanying glial activation in the visual pathway. Brain changes may occur in parallel with the RGC loss. Reactive glial cells in the brain may participate in the clearance of aberrantly released glutamate and may serve as a sensitive marker of neuronal injury. Neuroprotection of the entire visual pathway and glia-target therapies may bring new insights into the glaucoma treatment.

Fancheng Yan

Aier School of Ophthalmology

Central South University, Changsha, China

Partial Optic Nerve Transection in Rats: A Model Established with a New Operative Approach to Assess Secondary Degeneration of Retinal Ganglion Cells