Neuroprotective Effects of Brimonidine against Transient Ischemia-induced Retinal Ganglion Cell Death: a Dose Response in Vivo Study

Lafuente, M.P.; Villegas‐Pérez, María Paz; Mayor, Sergio; Aguilera, M.E.; Imperial, J Miralles de; Vidal‐Sanz, Manuel

doi:10.1006/exer.2001.1122

Cited by 72 publications

(36 citation statements)

References 36 publications

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“…During I/R, apoptosis plays a major role because oxygenderived reactive species (ROS) are known to trigger apoptosis [37,38]. Several studies have shown that application of exogenous free radical scavengers [3,9] and topically applied medications including PGA may reduce I/R-induced damage to the retina [2,20,26,29].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

et al. 2009

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This study was planned to investigate the neuroprotective potentials of three commercially available prostaglandin analogues (PGA), in the ischemia and reperfusion model (I/R). Thirty New Zealand rabbits were divided into 5 groups and except for the control group (non-ischemic, non-treated), 0.9% NaCl, bimatoprost, latanoprost, or travoprost were applied to both eyes of animals of the respective groups for 1 week. At the end of treatment, ischemia was induced in both eyes of the 4 treatment groups by anterior chamber irrigation of the animals for 60 min. Following 24 h reperfusion, the animals were sacrified. Enucleated eyes and retinal tissues were investigated by light microscopy, electron microscopy, immunohistochemicstry for retinal histopathology, intracellular and apoptotic cells and by retinal morphometry. Vitreous samples were biochemically investigated for probable role of reactive oxygen species, by measuring xanthine oxidase (XO) activity. Analysis of morphometric measurements and vitreous XO activity revealed significant differences between the PGAtreated groups and the NaCl-treated group (P<0.05). Similarly, apoptotic cell counts in different retinal layers showed that PGA-treated groups had fewer apoptotic cells in all retinal layers than the NaCl-treated ischemic group (P<0.05). PGA may have high protective potential for different retinal layers and cells. Biochemical analysis of vitreous showed that all PGAs decreased vitreous XO activity significantly compared to the NaCl-treated group (P<0.05). However we could not find any statistically significant differences among the analogues. PGAs may reduce the injury induced by I/R, through the inhibition of XO activity, and it seems that their effects are elicited through numerous pathways.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

et al. 2009

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“…1,2,4 In our earlier studies, topical application of BMD was found to confer a dose-dependent protective effect on RGCs. 17 BMD, according to the topical doses administered, prevented up to 90% of RCG loss. Between 7 and 21 days after ischaemia, there was an additional slow RGC loss, which could be significantly reduced by pretreatment with the highest BMD dose.…”

Section: Investigation Of Potential Neuroprotective Effects On Rgcsmentioning

confidence: 97%

Neuroprotection of retinal ganglion cell function and their central nervous system targets

Vidal‐Sanz

Villa

Avilés‐Trigueros

et al. 2007

Eye

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Technological advances have enabled the observation of a large number of retinal ganglion cells (RGCs) in an objective manner. In animal models, it has been shown how retinal ischaemia induces profound functional and structural alterations of the inner retinal and RGC layers by 3 months. These findings reflect degeneration of the inner retinal layers, the RGC population and of the retinotectal projection. Functionally, this implies a permanent disconnection of the retina from its main retinorecipient target region in the brain. Brimonidine, a selective a-2 adrenergic agonist, has been shown to activate a-2 adrenergic receptors in the retina and promote the survival and function of RGCs post-injury. This agent may prevent or diminish ischaemia-induced alterations in the inner and RGC areas as well as in the main retinofugal projection. Understanding the pattern of degeneration that occurs in the major retinofugal pathway following retinal ischaemia will benefit ongoing studies conducted to develop neuroprotectant-based treatment strategies for progressive neuropathies such as glaucoma.

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“…In another clinical trial, it was found to have intraocular pressure (IOP)-lowering efficacy greater than that of betaxolol (24). It is also shown to have neuroprotective actions on retinal ganglionic cells of the retina in glaucoma (25)(26)(27)(28)(29) thus making it as an important addition to the class of antiglaucoma agents that is not contraindicated in patients with cardiopulmonary disease (21,22). The loading of the drug in the nanoparticles could result in slower release over several hours, thus prolonging the IOP reduction and improved neuroprotective actions of BRT on RGC cells.…”

Section: Introductionmentioning

confidence: 99%

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

Bhagav

Upadhyay

Chandran³

2011

AAPS PharmSciTech

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Abstract. In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation technique for the treatment of open-angle glaucoma. The effect of various formulation variables like initial drug amount, lecithin proportion, phase volume and pH, secondary emulsifier and polymer proportion were studied. Various process variables like energy and duration of emulsification, lyophilization on the characteristics of nanoparticles and in vitro drug release profile were studied. The selected formulations were subjected to in vivo intraocular pressure-lowering efficacy studies by administering aqueous dispersion of nanoparticles into the lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based nanoparticles were found to have narrow particle size range and improved drug loading. The investigated process and formulation variables found to have significant effect on the particle size, drug loading and entrapment efficiency, and in vitro drug release profile of nanoparticles. The selected formulations upon in vivo ocular irritability and tolerability tests were found to be well tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies revealed that the selected nanoparticle formulations significantly improved the therapy as area under the ΔIOP vs. time curve [AUC (ΔIOP vs.t) ] showed several fold increase in intensity and duration of intraocular pressure (IOP) decrease. All the selected nanoparticle formulations were found to prolong the drug release in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a potential carrier in developing improved drug delivery systems for the treatment of glaucoma.

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Neuroprotective Effects of Brimonidine against Transient Ischemia-induced Retinal Ganglion Cell Death: a Dose Response in Vivo Study

Cited by 72 publications

References 36 publications

Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

Comparison of the Protective Effects of Prostaglandin Analogues in the Ischemia and Reperfusion Model of Rabbit Eyes

Neuroprotection of retinal ganglion cell function and their central nervous system targets

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

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