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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 10/2009

01-10-2009 | Basic Science

Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo

Authors: Akiyasu Kanamori, Maiko Naka, Masahide Fukuda, Makoto Nakamura, Akira Negi

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2009

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Abstract

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.
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Metadata
Title
Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo
Authors
Akiyasu Kanamori
Maiko Naka
Masahide Fukuda
Makoto Nakamura
Akira Negi
Publication date
01-10-2009
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2009
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-009-1122-6

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