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Hyewon Chung, Jung Jin Hwang, Jae Young Koh, June-gone Kim, Young Hee Yoon; Triamcinolone Acetonide-Mediated Oxidative Injury in Retinal Cell Culture: Comparison with Dexamethasone. Invest. Ophthalmol. Vis. Sci. 2007;48(12):5742-5749. doi: 10.1167/iovs.07-0566.
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purpose. To investigate the cytotoxicity of triamcinolone acetonide (TA) and dexamethasone (DXM) in various types of cells in retinal cell culture.
methods. Primary rat retinal cell cultures were treated with 25 to 800 μg/mL TA (58 μM–1.8 mM) or DXM (48 μM–1.6 mM) for 12 to 24 hours. Cell survival and death were assessed chemically by measuring cellular DNA contents using DNA-binding fluorescent dye and morphologically by propidium iodide staining. Standard methods were used for immunocytochemistry, immunoblots, and ELISA measurements. Retinal cellular oxidative stress was measured under a fluorescence microscope using 5-(and-6)-carboxy-2′,7′-difluorodihydrofluorescein diacetate. Changes in the level of several antioxidative proteins were investigated using immunoblots.
results. Exposure to 100 to 800 μg/mL TA (0.23–1.8 mM) or 800 μg/mL DXM (1.6 mM) for 24 hours caused a significant reduction in the number of retinal cells in culture, in a glucocorticoid receptor-independent manner. Of cell types in retinal cell cultures, astrocytes were most sensitive to TA and DXM. TA-induced cytotoxicity was mediated by oxidative stress. p38 kinase, c-Jun N-terminal kinase (JNK), caspase-1, and caspase-3 were involved in oxidative injury by TA. In addition, levels of antioxidative proteins increased after TA exposure.
conclusions. TA induces oxidative injury to cultured retinal cells in a glucocorticoid receptor-independent manner. These results suggest that TA has a significantly higher toxic potential in retinal cell culture than more water-soluble DXM. For long-term anti-inflammatory effects, devices that are designed for the sustained release of water-soluble steroids may be safer.
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