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Ralph Jensen; Antipsychotic drugs improve visual responses of ganglion cells in a rat model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3584.
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© ARVO (1962-2015); The Authors (2016-present)
In animal models of retinitis pigmentosa, there appears to be a reduction in the amount of dopamine released from retinal dopaminergic neurons. Since the activity of these neurons is regulated by dopamine D2 autoreceptors, I examined the effects of antipsychotic drugs, which are known to block dopamine D2 receptors, on light responses of retinal ganglion cells (RGCs) in a rat model of retinitis pigmentosa.
P23H-line 1 homozygous rats of 22–37 weeks of age were used in this study. Extracellular electrical recordings were made from RGCs in isolated retinas and an antipsychotic drug was applied to the bathing solution. RGC responses were measured to flashes of light over a range of light intensities, prior to and during bath application of an antipsychotic drug. Intensity-response curves were fitted with a sigmoidal dose-response (variable slope) using SigmaPlot 10.0. Three parameters were measured from the curve fits: maximum peak response, dynamic range, and light sensitivity.
The antipsychotic drugs haloperidol (0.5 µM), amisulpride (5 µM), clozapine (5 µM) and aripiprazole (5 µM) were each tested on 4-7 RGCs. Each antipsychotic drug increased light sensitivity of P23H rat RGCs, on average 0.26-0.39 log unit (Student’s t-test, P<0.05). No significant effects were observed on either the dynamic range or maximum peak response of the RGCs. Some ON-center RGCs in P23H rat retinas exhibited an abnormally long-latency (>200 ms) response to the onset of a small spot of light. All four antipsychotic drugs brought out a short-latency OFF response in these cells and tended to reduce the ON response.
My results in a rat model of retinitis pigmentosa show that antipsychotic drugs improve light sensitivity of RGCs and transform long-latency ON-center cells into OFF-center cells. It is surmised that the long-latency ON-center cells were - early in the course of the disease - OFF-center cells. It is postulated that the effects of the antipsychotic drugs are due to a blockade of dopamine D2 autoreceptors, resulting in an increased release of dopamine.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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