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Abstract #52002 Published in IGR 14-4
Effects of roscovitine, a cell cycling-dependent kinase inhibitor, on intraocular pressure of rabbit and retinal ganglion cell damage
Kasai H; Imamura T; Tsuruma K; Takahashi Y; Kurasawa T; Hirata H; Shimazawa M; Hara HNeuroscience Letters 2013; 535: 95-99
Glaucoma is characterized by increased intraocular pressure (IOP) and the death of retinal ganglion cells. Previously, we reported that roscovitine, a cell cyclin-dependent kinase (CDK) inhibitor, strongly induced relaxation of porcine trabecular meshwork cells, implicating an interaction with lowered IOP. In addition, the activity of CDKs is known to increase in response to high IOP, which is linked to retinal ganglion cell damage. However, the effects of roscovitine on IOP and retinal damage have not been investigated. Roscovitine has racemic isomers that differ in their inhibition of CDKs. Therefore, we investigated the effects of both the R-isomer and the S-isomer on the IOP of rabbits and on the death of cultured retinal ganglion cells. In the in vivo rabbit experiment, instillation of both isomers significantly lowered the IOP. In the in vitro cell experiment, the R-isomer amplified the effects of tunicamycin, an endoplasmic reticulum stress inducer, and increased oxygen-glucose deprivation-induced cell death, whereas S-isomer significantly inhibited this cell death. Therefore, both isomers of roscovitine can lower the IOP, but from the perspective of neuroprotective effects, the S-isomer was superior to the R-isomer. The S-isomer of roscovitine may be useful as an agent for lowering IOP and its neuroprotective effects.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan; Sagami Research Laboratories, Wakamoto Pharmaceutical Co, Ltd., 378 Kanade, Ohi-machi, Ashigarakamigun, Kanagawa 258-0018, Japan.
Full articleClassification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)
6.1.3 Factors affecting IOP (Part of: 6 Clinical examination methods > 6.1 Intraocular pressure measurement; factors affecting IOP)