Abstract
Purpose::
To compare cytotoxic effects of triamcinolone acetonide (TA) and dexamethasone (DXM) on various types of retinal cells and to investigate possible mechanisms of cytotoxicity and neuroprotection.
Methods::
Primary rat retinal cultures were obtained from newborn Sprague-Dawley rats and used for experiments after maturation (DIV≥10). Cells were treated with 25 - 800 ug/ml of TA and DXM for 24 hours. Cell viability and cell death were assessed . Immunocytochemistry and caspase assay were done.
Results::
With 24 hr treatment, TA caused significant reduction in the number of cultured retinal cells at concentrations of 100 - 800 ug/ml (p<0.001, all). On the contrary, DXM was toxic only at 800 ug/ml of DXM (p<0.001). Even with 12 hr treatment, 400 ug/ml TA induced a marked decrease in the number of GFAP (+) glial cells. Among neurons, Thy-1 (+) ganglion neurons were significantly decreased. In contrast, GABA (+) neurons were highly resistant. On the other hand, 12 h treatment with 400 ug/ml DXM was not toxic to any type of cells. Antioxidants significantly attenuated TA-induced retinal cytotoxicity. Caspase-1 activity as well as caspase-3 activity was upregulated after exposure to TA 400 ug/ml.
Conclusions::
Clinically achievable doses of TA is toxic to retinal cells, especially GFAP(+) glial cells after only a brief exposure (12 hr). Its cytotoxicity on retinal cells seems to be mediated via oxidative stress and caspase activation.
Keywords: retina • corticosteroids • retinal degenerations: cell biology