title: Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)-adrenoceptors and not by an action on imidazoline receptors.
abstract: Ischaemia was induced to the rat retina by raising the intraocular pressure above the systolic blood pressure for 45 min. After a reperfusion period of 5 days, alterations in the localisation of choline acetyltransferase (ChAT) and calretinin immunoreactivities, a reduction in the thickness of the inner retinal layers and a decline in the b-wave amplitude of the electroretinogram were recorded. These changes were blunted when clonidine was injected intraperitoneally before or after ischaemia or when applied topically by a specific regime. Other alpha(2)-adrenoceptor agonists, brimonidine and apraclonidine, acted in a similar way to clonidine when applied topically but because of the number of experiments carried out a comparison between the effectiveness of the different alpha(2)-adrenoceptor agonists was not possible. The protective effect of clonidine was attenuated when the alpha(2)-adrenoceptor antagonists yohimbine or rauwolscine were co-administered, suggesting that the mechanism of action of the drug is to stimulate alpha(2)-adrenoceptors. In addition, the imidazoline receptor ligands, BU-226 and AGN-192403 did not blunt the effect of ischaemia/reperfusion, supporting the notion that the protective action of the alpha(2)-adrenoceptor agonists does not involve imidazoline sites but rather the activation of alpha(2)-adrenoceptors. The protective effect of 0.5% clonidine appeared to be greater when topically applied to the eye that received ischaemia than when applied by the same regime to the contralateral eye. These studies suggest that while most of topically applied clonidine reaches the retina by a systemic route one cannot rule out additional pathways.
authors.affiliation: Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, OX2 6AW, Oxford, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Chao
authors.forename: N N
authors.initials: NN
authors.lastname: Osborne
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D064032:Calbindin 2; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004596:Electroretinography / Q000187:drug effects; D006536:Heptanes / Q000494:pharmacology; D054755:Imidazoline Receptors; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D011955:Receptors, Drug / Q000819:agonists / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D064030:S100 Calcium Binding Protein G / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C098523:AGN 192403; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001643:Bridged Bicyclo Compounds; C576512:Calb2 protein, rat; D064032:Calbindin 2; D006536:Heptanes; D054755:Imidazoline Receptors; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D064030:S100 Calcium Binding Protein G; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C016986:apraclonidine; D002795:Choline O-Acetyltransferase; D003000:Clonidine