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Richard A Lang, Russell N Van Gelder, P. Michael Iuvone, Shruti Vemaraju, Ethan Buhr, Sujata Rao, Minh-Thanh Nguyen; Dopamine is an Opsin 5-dependent modulator of vascular development in the eye. Invest. Ophthalmol. Vis. Sci. 2017;58(8):120.
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The non-canonical opsin OPN5 (Neuropsin) is known to be expressed in multiple tissues and to mediate light-dependent signaling. We have recently shown that OPN5 is expressed in a subset of retinal ganglion cells and is required for photoentrainment of the local circadian clock. We analyzed Opn5 null mice to determine whether there were changes in vascular development of the eye.
To analyze the eye phenotype of Opn5 null mice, we quantified hyaloid vessel regression and retinal angiogenesis over the first eight postanal days. This required flat-mount preparations of hyaloid vessels and retina and labeling of the vascular strctures with fluorescently-tagged isolectin. We also labeled the retina with antibodies to tyrosine hyroxylase and performed detection of dopamine in retina and vitreous using a sensitive ELISA.
Our analysis shows that Opn5 null mice show vascular development anomalies in the eye. These include a precocious regression of the hyaloid vessels and a mild overgrowth of the retinal vascular network. We also identified changes in the regulation of dopamine levels in the Opn5 null mouse. At day 5, Opn5 null mice show tyrosine hydoxylase expression anomalies and higher-than-normal levels of dopamine in the vitreous. To test the possibility that dopamine might directly regulate vascular development, we performed a conditional deletion of the dopamine receptor Drd2 in vascular endothelial cells. This produced a persistent hyaloid vessel network.
These data identify dopamine as a light- and Opn5-dependent mediator required for normal vascular development of the eye. These findings may explain why use of dopamine to treat hypotension in premature infants is a risk factor for severe retinopathy of prematurity.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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