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Ute Mathis; Immunohistochemical localization of alpha-2A adrenergic receptor in chicken retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5877.
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© ARVO (1962-2015); The Authors (2016-present)
Atropine, an unspecific muscarinic antagonist, is currently the most potent drug against myopia progression in children and various animal models. Recently, Carr et al. (IOVS 59, 2778-2791, 2018) have shown that atropine does not only bind to muscarinic receptors (M), but also to Alpha2A-Adrenoceptors (ADRA2As) and, different from chicken or human M4 receptors, binding to human ADRA2As correlates with inhibitory potency of myopia in the chicken. However, little is known about the distribution of ADRA2As in the chicken retina. We have undertaken an immunohistochemical study to analyze the cellular distribution of the Alpha2A-Adrenoceptor in the chicken fundal layers. For further characterization of the identified cells, double-labelling experiments with known retinal cell markers were performed.
Chicks received a monocular single intravitreal injection of 250 µg atropine which inhibited myopia by 100% in previous experiments. After 1.5h, the retinas of the atropine injected and vehicle injected fellow eyes were dissected and prepared for immunohistochemical analysis. We used antibodies against the alpha2A-adrenoceptor and different well established retinal cell markers.
(1) ADRA2As could be localized in ganglion cells, in cells of the inner nuclear layer, in inner and outer segments of photoreceptors, and at the outer limiting membrane. (2) We found colocalization of ADRA2A and tyrosine hydroxylase (TH) in dopaminergic amacrine cells. Interestingly, previous atropine injection reduced the number of double-labelled ADRA2A/TH-positive cells significantly (p<0.002). (3) Further colocalizations with retinal cell markers revealed ADRA2A immunoreactivity in cholinergic and non cholinergic amacrine cells, in inner segments of single cone photoreceptors and cone pedicles and in in few Islet1-positive ganglion cells. Marker for Müller Cells in chicken retina could be colocalized with ADRA2A at the outer limiting membrane.
Similar to muscarinic receptors (M1-5) which are widely expressed in the chicken retina, also ADRA2A appears to control the functions of many retinal neurons, including photoreceptors. It will therefore not be easy to delineate the cellular pathways by which atropine may suppress myopia development through ADRA2A.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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