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Erschienen in:
01.10.2009 | Basic Science
Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 10/2009
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Background
To investigate whether tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC).
Methods
RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca2+]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells.
Results
Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 μM (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca+2]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001).
Conclusions
These data suggest that tafluprost has an anti-apoptotic effect in RGCs.