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Abstract #24838 Published in IGR 11-4
Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo
Kanamori A; Naka M; Fukuda M; Nakamura M; Negi AGraefe's Archive for Clinical and Experimental Ophthalmology 2009; 247: 1353-1360
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 ([Ca(2+)]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 microM (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.
Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Japan. kanaaki@med.kobe-u.ac.jp
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
11.8 Neuroprotection (Part of: 11 Medical treatment)
