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Post-hypoxic constriction of retinal arterioles is impaired during nitric oxide and cyclo-oxygenase inhibition and in diabetic patients without retinopathy

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Abstract

Occlusion of retinal vessels leads to retinal ischaemia and hypoxia, which induces vasodilatation in adjacent retinal areas in order to normalize retinal oxygenation. Previous studies have shown that NO and COX products are involved in hypoxia-induced dilatation of retinal arterioles in vitro and in vivo, and that this response is disturbed in patients with diabetes mellitus. However, it is unknown to what extent post-hypoxic recovery of the diameter of retinal arterioles depends on NO and COX products in normal persons and in diabetic patients. The Dynamic Vessel Analyzer (DVA) was used to study the post-hypoxic diameter changes of larger retinal vessels in 20 normal persons, 20 diabetic patients without diabetic retinopathy, and in 18 patients with diabetic maculopathy before and after inhibition of the synthesis of nitric oxide and COX products. In normal persons, the arterioles had re-constricted (p > 0.99) 2 minutes after termination of hypoxia in the absence of antagonists, but not after treatment with L-NMMA and diclofenac (p < 0.01 for all comparisons). In diabetic patients without retinopathy, the arterioles showed no diameter changes after termination of hypoxia during any of the interventions. In patients with diabetic maculopathy hypoxia had not dilated retinal arterioles (p > 0.1 for all comparisons) to allow the study of re-constriction. In all groups, the dilatation of venules remained significantly increased during the post-hypoxic observation period, both in the absence and in the presence of L-NMMA and diclofenac.Post-hypoxic constriction of retinal arterioles depends on NO and COX products, and is impaired in diabetic patients before the development of retinopathy. This disturbance may contribute to the development of diabetic retinopathy, and should be the target of future interventional studies aimed at preventing and treating the disease.

ClinicalTrials.gov identifier: NCT01689090.

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Authors and Affiliations

  1. Department of Ophthalmology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark

    Line Petersen & Toke Bek

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  1. Line Petersen
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  2. Toke Bek
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Correspondence to Line Petersen.

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Funding

Synoptikfonden, Jochum Jensen & Mette Marie Jensens Foundation, Købmand Marie Kirstine Jensens Foundation Synoptikfonden, Fonden til Lægevidenskabens Fremme, Fight for Sight Denmark and the VELUX Foundation provided financial support in the form of funding of costs for the medications. The sponsors had no role in the design or conduct of this research.

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All authors certify that they have no affiliationswith or involvement in any organization or entity with any financial interest (such as honoraria;educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

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All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Petersen, L., Bek, T. Post-hypoxic constriction of retinal arterioles is impaired during nitric oxide and cyclo-oxygenase inhibition and in diabetic patients without retinopathy. Graefes Arch Clin Exp Ophthalmol 255, 1965–1971 (2017). https://doi.org/10.1007/s00417-017-3746-2

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