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Oliver W. Gramlich, Harald D. von Pein, Anika Ziegler, Kathrin Bitz, Norbert Pfeiffer, Franz H. Grus; Topical Treatment With A Selective COX-2 Inhibitor Promotes Retinal Ganglion Cell Survival After Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6273.
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Our previous studies revealed that a selective cyclooxygenase 2 (COX-2) inhibitor promotes neuronal cell survival in cell culture. Now, the study aim was to examine if a COX-2 inhibition with Celecoxib® promotes retinal ganglion cell (RGC) survival after optic nerve crush and could reduce inflammation, especially microglial activation.
30 Lewis rats underwent unilateral optic nerve crush (ONC) under ketamine/xylazine anesthesia. Animals received Celecoxib orally (50mg/kg; n=10) or topically (0.1%, 30 µl; n=10) twice a day. 10 animals served as control with no medical treatment. In five animals per group, neuronal density in the ganglion cell layer was evaluated on cresyl stained retinal flatmounts after ten days. Correspondingly, axon counts of optic nerve sections were performed via toluidine blue staining. In the other five animals per group, cellular infiltrates and optic nerve architecture were examined after H&E and Luxol Fast blue staining in serial horizontal optic nerve sections. Microglia was investigated in detail via anti-Iba 1 immunostaining. Amounts of infiltrates were graded by a 0 (no infiltrates) to 3 (strong infiltration) scoring and microglia was evaluated semi-quantitative.
No changes in cell and axon density were detected in untreated eyes. At the crushed site, cell and axon density differed not in the oral treated group (1938±372 cells/mm²; 303±83 axons) and the controls with no medication (1922±455 cells/mm²; 278±135 axons). Therefore, the topical treated group showed a significantly increased RGC density and axons (2156±587 cells/mm², p=0.04; 595±161 axons, p<0.001). In this group, the laminar structure of myelin in the optic nerves was predominantly intact and accompanied by a significantly reduction of cell infiltrates (p=0.01). At least, microglial activity was decreased in animals with topical administration.
A selective COX-2 inhibition reduces infiltration and microglial activity after optic nerve crush and promotes RGC survival. The topical modulation of the cellular immune response by COX-2 inhibition might be a new and sufficient feature for neuroprotection and seems more suitable than a general systemic modulation.
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