Research into aqueous humour production and its control within the bovine eye

Williams, Graeme (2005) Research into aqueous humour production and its control within the bovine eye. PhD thesis, University of Glasgow.

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The isolated, perfused bovine eye model has a long proven track record as an established experimental model allowing the study of the physiology and pharmacology of aqueous humour. Wilson et al, 1993 have shown this model in numerous experiments to provide reproducible results, consistent with in vivo models. Shahidullah et aL (1995, 1999) have since taken the use of the model ftirther showing a number of categories of drugs that reduce aqueous production and hence intraocular pressure. Bradykinin (10-9 to 10-8M) suppressesaqueous humour formation (42-49% reduction). At higher concentrations (3x10-8Mand 10-7M) aqueous production appeared to be increased (8-15% increase).It is possible that suppression of aqueous humour formation persists at higher bradykinin concentrations but at higher concentrations leakage of fluid from the vascular compartment into the chamber of the eye occurs -breakdown of the blood- aqueous barrier. Bradykinin was found to act through the B2 receptor. WIN 64338 (3x10-8M), a B2 receptor antagonist, abolished the effect of bradykininon aqueous humour formation suppression (unpaired t-test: p<0.01). L-NAME (10-4M), a nitric oxide synthase inhibitor, significantly reduced the effectof bradykinin (10-9M) on aqueous humour formation (bradykinin (10-9M) alone42% reduction, in presence of L-NAME 14% reduction: unpaired t-test p<0.01). L-NAME alone (10-4M) had no significant effect on aqueous humour formation(paired t-test >0.1) suggesting that there is no tonic influence of endogenous nitric oxide in the bovine ciliary epithelium. Bradykinin appears to suppress aqueous humour formation via nitric oxide and cGMP since a soluble guanylate cyclase inhibitor (ODQ) also blocked the bradykinin- induced inhibition of aqueous humour formation (bradykinin (10-9M) alone 42% reduction, in presenceof ODQ (3x10-7M) 4% reduction: unpaired t-test p<0.004). The absence of ascorbate from the perfusate significantly reduced the inhibitory effect of bradykinin on aqueous humour production (bradykinin (10-9M) in presence ofascorbate 42% reduction, bradykinin (10-9M) in absence of ascorbate 5% reduction:unpaired t-test p<0.004). It is possible that the vasodilator effect of bradykinin in the absence of ascorbate (McNeish et al, 2003) may counter the effect on aqueous humour formation. The close parallel between the very low concentrations of bradykinin required to suppress aqueous humour formation and to affect intracellular calcium movements, supports the hypothesis that intracellular calcium plays an important role in aqueous humour formation. It may also suggest a physiological role for bradykinin as a modulator in the ciliary epithelium. (Abstract shortened by ProQuest.)

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Ophthalmology.
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Supervisor, not known
Date of Award: 2005
Depositing User: Enlighten Team
Unique ID: glathesis:2005-71451
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 14:38
Last Modified: 28 Jul 2021 14:09

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