| dc.contributor.author | Szczesniak, Anna-Maria. | en_US |
| dc.date.accessioned | 2014-10-21T12:35:28Z | |
| dc.date.available | 2005 | |
| dc.date.issued | 2005 | en_US |
| dc.identifier.other | AAINR08418 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/54750 | |
| dc.description | Intraocular pressure (IOP) is determined by both aqueous humor (AH) production and AH outflow facility. This research examined the pharmacokinetic and pharmacodynamic profiles of liposomal Delta9-tetrahydrocannabinol (LTHC) on IOP in Brown Norway rats and New Zealand White rabbits. The IOP effects of LTHC were compared to that of other cannabinoids. The additive IOP effect of LTHC together with beta-blocker (timolol) and prostaglandin analogue (latanoprost) was also investigated. The cannabinoid cellular mechanisms were studied in trabecular meshwork (TM) cells, which line the AH outflow pathway. | en_US |
| dc.description | In rats, LTHC was given by intratracheal (i.t.) instillation or via intraperitoneal (i.p.) injection. WIN55,212-2, methanandamide (MA) and cannabinoid receptor 1 (CB1R) antagonist SR141716A were administered i.p., while timolol and latanoprost were applied topically. In rabbits, LTHC was administered i.t., i.v., or topically. IOP readings were taken every 15 minutes for 2 hours. For the pharmacokinetic experiments, topical, i.t. and i.v. LTHC was administered to rabbits. Ocular tissues were harvested and the Delta9-THC was determined by gas chromatography/mass spectrometry. The expression of CB1Rs in rat ocular tissues was confirmed with RT-PCR, Western Blot analysis and immunohisochemistry. The effects of CB1Rs activation on cell signalling pathways in TM cells were investigated with Western Blot analysis, phalloidin staining of filamentous actin, and Optical Magnetic Twisting Cytometry (OMTC) analysis. | en_US |
| dc.description | LTHC, MA and WIN55,212-2 reduced IOP in rat eyes. These IOP-lowering effects were blocked by SR141617A. No additive effect was observed when Timolol or Latanoprost was added to LTHC. The biologically relevant amounts of Delta9-THC were detected in rabbit ocular tissues following topical, i.t. and i.v. LTHC administrations. | en_US |
| dc.description | Cannabinoid and muscarinic agonists resulted in an increased MLC phosphorylation and changes in TM cell morphology consistent with an increase in contractility and trabecular resistance. | en_US |
| dc.description | In conclusion, LTHC administration decreased IOP in animals and resulted in physiological levels of Delta9-THC in ocular tissues. The presence of CB1Rs in TM and modulation of TM cell contractility by cannabinoid agonists suggest a potential role for these compounds in regulation of AH outflow. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2005. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.title | Effects of cannabinoid agonists in the mammalian eye. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
