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Cheryl M. Craft, Bruce M. Brown, Eun-Jin Lee, Joseph Pak, Jane Abey, Machelle T. Pardue, P. M. Iuvone; Enhanced Retinal Dopamine Metabolism in Visual Arrestin 1 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):759.
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© ARVO (1962-2015); The Authors (2016-present)
With light exposure, retinal dopamine (DA) is synthesized, released, and metabolized. It has been suggested that dopamine promotes light adaptation, which results in a complex transition from mesopic to photopic vision. When visual Arrestin 1 (Arr1) is not expressed in rod and cone photoreceptors, the b-wave amplitude of the photopic electroretinogram (ERG) does not increase over a 15 min period of rod-saturating background illumination, as it does in wild type (WT) and cone Arr4-/- mice (Brown et al., IOVS 2010;51:2372); thus light adaptation is absent. Based on this defective photopic ERG phenotype, we hypothesized that DA might be reduced in Arr1-/- mouse retina and examined the involvement of inner retinal pathways, including GABA, Glyt-1, synaptic markers, and a gap junction protein.
Mice (Arr1-/-) and WT controls were dark-reared and then light-exposed for 2 hrs. Retinas were analyzed by immunohistochemistry (IHC) and immunoblot analysis for GAD65/67, Glyt-1, vGlut1, Connexin 36, Bassoon, PSD95 and tyrosine hydroxylase (TH). Additional retinas were analyzed for dopamine and DOPAC, the primary DA metabolite in the retina, using high-performance liquid chromatography (HPLC) with coulometric detection.
After light-exposure for 2 hrs, retinas from Arr1-/- had no significant immunoreactive differences in the selected retinal markers with the exception of enhanced immunoreactive TH expression in the amacrine cells, compared to WT controls. In agreement with the changes in TH expression, steady-state levels of DA and DOPAC were significantly higher in the retinas of Arr1-/- mice than in WT controls.
In retinas of Arr1-/-, we have evidence of enhanced synthesis and breakdown of DA compared to WT. Thus, it is unlikely that reduced DA contributes to abnormal photopic responses of mice lacking Arr1 in rod and cone photoreceptors. However, the data do not exclude the possibility that Arr1 expression, but not Arr4, is necessary for dopamine D4 receptor regulation of photoreceptor function.
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