Abstract
Purpose: :
The aim of the present study was to investigate the role of D3 receptor on intraocular pressure regulation using WT and KO D3R-/- mice
Methods: :
All experiments were carried out on KO D3R-/- and WT mice. Both mice were used with normal eye pressure or steroid-induced ocular hypertension. All the animals were treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Identification of dopamine receptors transcripts in iris-ciliary body (ICB) tissue samples was carried out by RT-PCR. Mouse ICB levels of 7-OH-DPAT, a dopamine D3-preferring receptor agonist, topically instilled in the mouse’s eye were determined by HPLC analysis
Results: :
As measured by tonometry, the topical application of 7-OH-DPAT, significantly decreased, in a dose-dependent manner (0.01, 0.1, 1 and 5% w/v), the intraocular pressure in WT mice both in an ocular normotensive group and an ocular hypertensive group. Pretreatment with U-99194A, a D3 receptor antagonist, reverted 7-OH-DPAT induced ocular hypotension in WT mice. No change of intraocular pressure was observed after topical application of 7-OH-DPAT in KO D3R-/- mice. PCR analysis demonstrated the presence of all dopamine receptor genes in eye tissues obtained from WT mice, and the lack of D3R mRNAs in KO mice. Levels of 7-OH-DPAT (0.147μg/mg) were detected, by HPLC analysis, in the iris-ciliary body 30 min after single topical administration of 0.1% eye drops
Conclusions: :
The present study identified the D3R subtype as the most important receptor of the dopaminergic system to modulate intraocular pressure with relevant implications for glaucoma
Keywords: dopamine • intraocular pressure • drug toxicity/drug effects