Protective effects of timolol against the neuronal damage induced by glutamate and ischemia in the rat retina

Protective effects of timolol against the neuronal damage induced by glutamate and ischemia in... The purpose of this study was to determine whether timolol, an ocular hypotensive drug, has retinal neuroprotective effects in experimental in vitro and in vivo models. For in vitro studies, we used retinal neuron cultures from rat embryos and purified retinal ganglion cells (RGCs) from newborn rats. In the former, neurotoxicity was induced using 1 mM glutamate and cell viability was assessed. In RGCs, neurotoxicity was induced using 25 μM glutamate for 3 days and cell viability was assessed. For the in vivo study, we used a rat model of retinal ischemic injury induced by elevating intraocular pressure (IOP) by raising the hydrostatic pressure. The retinal damage was evaluated by counting the number of cells in the ganglion cell layer (GCL) and by examining the a- and b-waves in the electroretinogram (ERG). For the intraocular distribution study, 0.5% ( 3 H)timolol was topically applied to rat eyes, and these were enucleated after various intervals and divided into parts. Each part was combusted and the radioactivity measured. Timolol (0.1 and 1 μM) markedly reduced the glutamate-induced neuronal cells in retinal neuron cultures and in RGCs. After ischemic-reperfusion, both the number of cells in the GCL and a- and b-waves in the ERG decreased; however, topically applied 0.5% timolol reduced these effects. Topically applied 0.5% timolol was detected at a concentration of ∼1 μg/g wet tissue in retina-choroid at 30 min after its application. In conclusion, timolol was effective against retinal neuron damage both in vitro and in vivo. Furthermore, topically applied timolol reached the retina-choroid. These findings suggest that timolol has a direct neuroprotective effect against retinal damage. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Protective effects of timolol against the neuronal damage induced by glutamate and ischemia in the rat retina

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science B.V.
ISSN
0006-8993
D.O.I.
10.1016/S0006-8993(02)03372-3
Publisher site
See Article on Publisher Site

Abstract

The purpose of this study was to determine whether timolol, an ocular hypotensive drug, has retinal neuroprotective effects in experimental in vitro and in vivo models. For in vitro studies, we used retinal neuron cultures from rat embryos and purified retinal ganglion cells (RGCs) from newborn rats. In the former, neurotoxicity was induced using 1 mM glutamate and cell viability was assessed. In RGCs, neurotoxicity was induced using 25 μM glutamate for 3 days and cell viability was assessed. For the in vivo study, we used a rat model of retinal ischemic injury induced by elevating intraocular pressure (IOP) by raising the hydrostatic pressure. The retinal damage was evaluated by counting the number of cells in the ganglion cell layer (GCL) and by examining the a- and b-waves in the electroretinogram (ERG). For the intraocular distribution study, 0.5% ( 3 H)timolol was topically applied to rat eyes, and these were enucleated after various intervals and divided into parts. Each part was combusted and the radioactivity measured. Timolol (0.1 and 1 μM) markedly reduced the glutamate-induced neuronal cells in retinal neuron cultures and in RGCs. After ischemic-reperfusion, both the number of cells in the GCL and a- and b-waves in the ERG decreased; however, topically applied 0.5% timolol reduced these effects. Topically applied 0.5% timolol was detected at a concentration of ∼1 μg/g wet tissue in retina-choroid at 30 min after its application. In conclusion, timolol was effective against retinal neuron damage both in vitro and in vivo. Furthermore, topically applied timolol reached the retina-choroid. These findings suggest that timolol has a direct neuroprotective effect against retinal damage.

Journal

Brain ResearchElsevier

Published: Dec 20, 2002

References

  • Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina
    Adachi, K.; Fujita, Y.; Morizane, C.; Akaike, A.; Ueda, M.; Satoh, M.; Masai, H.; Kashii, S.; Honda, Y.
  • Glutamate neurotoxicity in cortical cell culture
    Choi, D.W.; Maulucci-Gedde, M.; Kriegstein, A.R.
  • Prospects for relevant glaucoma models with retinal ganglion cell damage in the rodent eye
    Goldblum, D.; Mittag, T.
  • Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma
    Haefliger, I.O.; Dettmann, E.; Liu, R.; Meyer, P.; Prunte, C.; Messerli, J.; Flammer, J.
  • Dual actions of nitric oxide in N -methyl- d -aspartate receptor-mediated neurotoxicity in cultured retinal neurons
    Kashii, S.; Mandai, M.; Kikuchi, M.; Honda, Y.; Tamura, Y.; Kaneda, K.; Akaike, A.
  • Neuroprotection in relation to retinal ischemia and relevance to glaucoma
    Osborne, N.N.; Ugarte, M.; Chao, M.; Chidlow, G.; Bae, J.H.; Wood, J.P.; Nash, M.S.
  • Periocular accumulation of timolol and betaxolol in glaucoma patients under long-term therapy
    Sponsel, W.E.; Terry, S.; Khuu, H.D.; Lam, K.W.; Frenzel, H.
  • New approaches to antiglaucoma therapy
    Sugrue, M.F.

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