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The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis

  • Retinal Disorders
  • Published:
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Abstract

Purpose

Diabetic retinopathy is accompanied with changes in the diameter regulation and oxygenation of retinal vessels. Previous studies have shown that in normal persons and in diabetic patients without retinopathy hypoxia-induced vasodilatation is mediated by cyclo-oxygenase (COX) products and nitric oxide (NO). The purpose of the present study was to study whether these effects can be reproduced in patients with diabetic maculopathy.

Methods

Eighteen patients with diabetic maculopathy aged 29–57 years were examined using the Dynamic Vessel Analyzer. The resting diameter and the diameter changes of retinal arterioles during isometric exercise and flicker stimulation were studied before and during breathing a hypoxic gas mixture. The examinations were also performed before and during intravenous infusion of the NOS inhibitor L-NMMA, and were repeated on a second day after topical administration of the COX-inhibitor diclofenac.

Results

The diameter of retinal arterioles showed no significant change during hypoxia or L-NMMA infusion, or after topical application of diclofenac (p > 0.25 for all comparisons). The resting diameter of the venules was significantly increased during hypoxia (p = 0.003) and decreased during L-NMMA infusion (p < 0.0001). The diameter of retinal venules during isometric exercise increased significantly during hypoxia (p = 0.01). Flicker stimulation induced significant dilatation of the venules, which was significantly reduced during hypoxia and increased during L-NMMA infusion (p < 0.0001 for all comparisons).

Conclusion

Hypoxia-induced dilatation of retinal arterioles is severely reduced in patients with diabetic maculopathy. Future intervention studies aimed at normalizing the diameter regulation of retinal arterioles in diabetic patients should preferentially be conducted in the early stages of the disease where the potential for changing the vessel diameter is preserved.

ClinicalTrials.gov identifier: NCT01689090

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Acknowledgments

The study was supported by Fight for Sight Denmark and the VELUX Foundation, who had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.

The authors had full control of the primary data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.

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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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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

Fight for Sight Denmark and the VELUX Foundation provided financial support for the purchase of the medication L-NMMA. The sponsors had no role in the design or conduct of this research.

Ethical approval

All procedures performed in the study were in accordance with the ethical standards of the regional Committee for Scientific Ethics and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Petersen, L., Bek, T. The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis. Graefes Arch Clin Exp Ophthalmol 254, 2339–2346 (2016). https://doi.org/10.1007/s00417-016-3399-6

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  • DOI: https://doi.org/10.1007/s00417-016-3399-6

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