Arterially perfused eye model of uveitis.
Abstract: To develop an in vitro model of uveitis based on an ex situ perfused eye to evaluate the anti-inflammatory activity of new pharmacological products. Methods: Eyes were removed from more than 60 dogs and 9 horses immediately after euthanasia and perfused with nutrient medium through the lateral long ciliary artery. Perfused eyes produced aqueous humour, and perfusion pressure was adjusted to obtain an intraocular pressure in the physiological range. When the eyes were treated with histamine, a complement C5a analogue peptide and hydrogen peroxide, typical signs of uveitis were produced. These included miosis, vascular leakage, reduced intraocular pressure, reduced flow of perfusate and, in some eyes, conjunctival oedema. Results: Canine eyes showed a decrease in intraocular pressure and a decrease in perfusate flow rate when challenged with 100 mumol/L hydrogen peroxide. Flunixin meglumine (5 mumol/L), ketoprofen (5 mumol/L), indomethacin (5 mumol/L) as well as a new drug pirfenidone (10 mumol/L) prevented changes in intraocular pressure induced by hydrogen peroxide, but did not significantly moderate the mediator-induced changes in perfusate flow. Conclusions: This model is suitable for evaluating potential anti-inflammatory activity of drugs without having to induce uveitis in an experimental animal. The technique is suitable for species that range in size from cats to horses.
Publication Date: 1999-03-17 PubMed ID: 10078357DOI: 10.1111/j.1751-0813.1999.tb11677.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper is concerned with the development of an in vitro (laboratory-based) model of uveitis, a type of inflammation of the eye, to allow for evaluation of potential anti-inflammatory drugs. The model uses the eyes of animals and can operate without the need for live animals.
Objective and Methodology
- The objective of the research was to create an in vitro model of uveitis. This model would allow researchers to evaluate the anti-inflammatory effects of new drugs without evoking inflammation in live animals.
- The technique used to create this model involved the removal of eyes from over 60 dogs and 9 horses post-euthanasia. They were then perfused (have fluid pumped through) with a nutrient medium via the long lateral ciliary artery, which mimicked natural blood flow.
- By adjusting the perfusion pressure, intraocular pressure in the physiological range was achieved. This pressure is akin to the normal eye pressure in an organism.
- Uveitis symptoms such as miosis (constricted pupils), vascular leakage, reduction in intraocular pressure, and a decreased flow of perfusate, were induced in the model eyes with the use of histamine, a complement C5a analogue peptide, and hydrogen peroxide.
Findings
- Within the canine eyes used in the model, there was a decrease in intraocular pressure and a decrease in the flow rate of the perfusate when challenged with 100 mumol/L hydrogen peroxide.
- Several drugs, including Flunixin meglumine, ketoprofen, indomethacin, and a new drug pirfenidone, were tested to determine their ability to prevent the changes in intraocular pressure induced by hydrogen peroxide.
- The effects of these drugs on mitigating the changes birng quite promising. Particularly, they maintained regular intraocular pressure, although they did not significantly moderate the changes in perfusate flow.
Conclusion
- This novel model has been shown to be effective for testing potential anti-inflammatory drugs, reducing the need for inducing uveitis in live animals, making it more ethical for drug testing.
- Moreover, the model has demonstrated applicability across a range of species from cats to horses, which implies its wide usability.
Cite This Article
APA
Shiels IA, Sanderson SD, Taylor SM.
(1999).
Arterially perfused eye model of uveitis.
Aust Vet J, 77(2), 100-104.
https://doi.org/10.1111/j.1751-0813.1999.tb11677.x Publication
Researcher Affiliations
- Department of Physiology and Pharmacology, University of Queensland, St Lucia.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
- Cats
- Ciliary Arteries / drug effects
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Clonixin / therapeutic use
- Complement C5a / adverse effects
- Complement C5a / antagonists & inhibitors
- Disease Models, Animal
- Dogs
- Eye / physiopathology
- Female
- Histamine / adverse effects
- Horse Diseases / drug therapy
- Horses
- Hydrogen Peroxide / adverse effects
- Indomethacin / pharmacology
- Indomethacin / therapeutic use
- Intraocular Pressure / drug effects
- Ketoprofen / pharmacology
- Ketoprofen / therapeutic use
- Male
- Perfusion / methods
- Perfusion / veterinary
- Pyridones / pharmacology
- Pyridones / therapeutic use
- Uveitis / drug therapy
- Uveitis / veterinary
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