Interactions between GABAergic, dopaminergic and cholinergic neurotransmitter systems in form deprived myopic chick

摘要

Myopia is a refractive defect of the eye in which collimated light produces images focused in front of the retina. Myopia can be artificially induced in animal models by form deprivation (form deprivation myopia, FDM) or by application of negative lenses (lens induced myopia, LIM). In this study myopia was induced using diffusers. The project had two main aims:udud1.To determine if there is an interaction between the GABAergic system and dopaminergic system in the retina in terms of myopia?ud2.To determine if there is an interaction between the GABAergic system and cholinergic system in the retina in terms of myopia?ududFirstly, an experiment focusing on the interaction between dopaminergic receptors antagonists and GABAC receptor antagonist was developed. Comparison of the different drug treated eye with the control was found and the effects of combination injections were compared to individual drug injections. Use of different blockers for various subtype of receptors simplified the understandings the underlying pharmacological interventions for GABAC receptor antagonist TPMPA. The D1 subtype of receptors was found to be involved in transmission of signals from GABAC receptors. Our results showed that D1 receptor antagonist SCH-23390 antagonizes the actions of TPMPA. In addition to this it was also found that possibly 5HT receptor may also play an important role in modulation of signaling from GABA receptor to dopaminergic receptors in the retina. These results were consistent with the drug combination effects for agonists. GABA A/C receptor agonist muscimol negativate the efficacy of D1 receptor agonist SKF-38393 but the activity of D2/4 receptor agonist quinpirole was not affected by muscimol. ududAlthough dopaminergic receptors are found to interact with GABAergic signaling, but an alternative interaction with anticholinergic (most widely studied antimyopic agents) could not be ruled out. This problem led to a follow-up experiment, in which GABA receptors intervention in anticholinergic agents was studied.ududThe GABAergic receptor agonist muscimol when injected with anticholinergics (atropine and pirenzepine) showed a moderate interaction. As muscimol interacted with atropine to a lesser extent a more specific M1/5 receptor antagonist pirenzepine (earlier found to inhibit myopia) was used under these circumstances. The second aim to study the interaction between muscimol and pirenzepine showed more interaction with GABAA/C receptor agonist. There were data suggesting that there is a muscarinic and GABAergic interaction in retina, such that each modulation of each receptor had an effect on FDM. However, a drug combination treatment helped in understanding the underlying mechanism. Several previous studies have indicated that there exist a strong interaction between excitatory neurotransmitter acetylcholine and inhibitory transmitter GABA in retina. The results of this study indicate a similar finding. ududThus results of this study may be summarized as: 1. D1 antagonists and not D2 antagonists blocks the antimyopic effects of GABAC antagonist TPMPA 2. GABA A/C agonist muscimol partially blocks the antimyopic activity of anticholinergics (e.g. atropine and pirenzepine).