Constitutive Expression and Localization of COX-1 and COX-2 in Rabbit Iris and Ciliary Body

Damm, Julia; Rau, Thomas; Maihöfner, Christian; Pahl, Andreas; Brune, Kay

doi:10.1006/exer.2001.0977

Cited by 34 publications

(34 citation statements)

References 26 publications

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“…On the basis of studies that show a widespread distribution of COX-2 within the central nervous system, the object of recent studies (Damm et al, 2001;Maihöfner et al, 2001) was the localization of the COX-2 enzyme in the eye, which ontogenetically originates from the neuroepithelium and shares many characteristics with the central nervous system. Since prostaglandins have been introduced in primary open angle glaucoma (POAG) with great success, the study performed by Maihöfner et al (2001) has focused on the question whether a change in the expression of the COX isoforms might be involved in the pathogenesis of POAG.…”

Section: Cox-2 In the Central Nervous Systemmentioning

confidence: 99%

Cyclooxygenase-2—10 Years Later

Hinz

Brune²

2002

J Pharmacol Exp Ther

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450

298

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The enzyme cyclooxygenase (COX) catalyzes the first step of the synthesis of prostanoids. In the early 1990s, COX was demonstrated to exist as two distinct isoforms. COX-1 is constitutively expressed as a "housekeeping" enzyme in most tissues. By contrast, COX-2 can be up-regulated by various proinflammatory agents, including lipopolysaccharide, cytokines, and growth factors. Whereas many of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., gastrointestinal ulceration and bleeding, platelet dysfunctions) are caused by a suppression of COX-1 activity, inhibition of COX-2-derived prostanoids facilitates the anti-inflammatory, analgesic, and antipyretic effects of NSAIDs. During the past few years specific inhibitors of the COX-2 enzyme have emerged as important pharmacological tools for treatment of pain and arthritis. However, although COX-2 was initially regarded as a source of pathological prostanoids only, recent studies have indicated that this isoenzyme mediates a variety of physiological responses within the organism. The present review assesses recent advances in COX-2 research, with particular emphasis on new insights into pathophysiological and physiological functions of this isoenzyme.

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Section: Cox-2 In the Central Nervous Systemmentioning

confidence: 99%

Cyclooxygenase-2—10 Years Later

Hinz

Brune²

2002

J Pharmacol Exp Ther

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450

298

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“…The nonselective NSAID group inhibits both COX-1 and COX-2 enzymes. Although inhibition of COX-2 enzyme is required for inhibition of the production of inflammatory prostaglandins (PGs), inhibition of COX-1 enzyme is not required because it leads to inhibition of the production of physiological PGs involved in the normal regulation of intraocular pressure and blood aqueous barrier (8). Nimesulide is a NSAID that belongs to COX-2 preferential inhibitors.…”

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confidence: 99%

Comparison between two cyclooxygenase inhibitors in an experimental dry eye model in albino rabbits

Elshazly¹,

Elgohary²,

Elshazly³

et al. 2008

Acta Pharmaceutica

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Dry eye syndrome, or keratoconjunctivitis sicca (KCS), is one of the most frequent ocular disorders. It may lead to progressive corneal opacification and blindness (1). Secretory, neuronal and mechanical processes that regulate the production and mixing of tear film constituents are functionally integrated (2). The ageing process, hormonal, environmental, iatrogenic, pharmacological and pathogenic factors may disrupt the tear film with subsequent ocular surface inflammation (3). The hyperosmolar tear film stimulates the production of mitogen-activated protein kinase (4). This initiates a cascade of protein phosphorylation involving other kinases and nuclear transcription factors which stimulate the proinflammatory cytokines and chemokines in tear fluid and conjunctival epithelium in KCS (5). The purpose of this study was to compare the topical anti-inflammatory effects of the nonselective cyclooxygenase (COX) inhibitor, ketorolac, with the selective COX-2 inhibitor, nimesulide, in an animal model of dry eye in albino rabbits. All animals were examined by the Schirmer test, tear break-up time (TBUT) and fluorescein corneal staining test. Dry eye model showed significant reduction in tear volume, TBUT, corneal staining and histopathological signs of dryness and inflammation. On treating dry eye model with nimesulide 0.1% eye drops and ketorolac 0.5% eye drops, there were improvements in Schirmer test values, TBUT and fluorescein corneal staining and histopathologically reduced inflammatory reaction, with signs of healing and regeneration. Both nimesulide and ketorolac ameliorate atropine sulphate induced dry eye in albino rabbits. The use of selective COX-2 inhibitor, nimesulide, is preferred to avoid local and systemic side effects which may occur with the use of the nonselective COX inhibitor, ketorolac.

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“…27 In addition, there is evidence that the COX-2 enzyme is expressed constitutively in both the anterior and posterior segments of the human eye. 28,29 In the present study, inflammation was assessed based upon both PGE 2 aqueous concentrations as well as by the degree of FITC-dextran leakage from the iris blood vessels secondary to the breakdown of the blood-aqueous barrier. Further studies are necessary to assess whether measurement of FITC-dextran leakage is a more sensitive marker of inflammation than PGE 2 levels.…”

Section: Figmentioning

confidence: 99%

“…For purposes of this and previous studies, both COX-1 and COX-2 enzymes are expressed in the iris and ciliary body of rabbits. 28,29 The design of the study and the administration of 3 doses over the course of an hour before LPS injection was intended to simulate a typical preoperative dosing regimen, 18 but the timing of medication instillation in this study may not exactly correlate with various dosing regimens that may be employed perioperatively. The injection of LPS at hour 10 in the trough group was intended to evaluate the ability of the NSAID to suppress inflammation at trough levels of active agent.…”

Section: Figmentioning

confidence: 99%

Ocular Penetration and Anti-inflammatory Activity of Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-Induced Inflammation

Waterbury¹,

Galindo

Villanueva

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model. Methods: At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)-dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC 50 ) for COX isoenzymes. Results: Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E 2 and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E 2 elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC 50 for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC 50 for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels. Conclusions: Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC-dextran leakage. The difference in inflammation suppression may be due to differences in tissue concentrations and/or greater COX-1 suppression by ketorolac 0.45%.

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Constitutive Expression and Localization of COX-1 and COX-2 in Rabbit Iris and Ciliary Body

Cited by 34 publications

References 26 publications

Cyclooxygenase-2—10 Years Later

Cyclooxygenase-2—10 Years Later

Comparison between two cyclooxygenase inhibitors in an experimental dry eye model in albino rabbits

Ocular Penetration and Anti-inflammatory Activity of Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-Induced Inflammation

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