Abstract
Purpose
The retinal relaxing factor (RRF) is a continuously released factor from the retina that causes vasorelaxation, the identity and potential role in physiology of which remain largely unknown. Experiments were performed to find out whether the RRF-induced relaxation is influenced by serotonin, glutamate, L-cysteine, the cytochrome P450 pathway, the cyclooxygenase pathway, or oxidative stress. In addition, the sensitivity of retinal and non-retinal arteries towards the RRF was compared.
Methods
In vitro tension measurements were performed on isolated mouse femoral or bovine retinal arteries to study the vasorelaxing effect of the RRF, induced by mouse or bovine retinas.
Results
The presence of serotonin, glutamate, or L-cysteine did not alter the RRF-induced relaxation. Increasing oxidative stress by hydroquinone and diethyldithiocarbamic acid sodium salt enhanced the RRF response. Inhibition of the cytochrome P450 or the cyclooxygenase pathway did not cause any alteration. Surprisingly, the RRF-induced relaxation was enhanced by the presence of flufenamic acid or carbenoxolone. Furthermore, bringing retinal tissue in close contact with retinal or non-retinal arteries induced comparable relaxations.
Conclusions
Serotonin, glutamate, L-cysteine, the cytochrome P450, and the cyclooxygenase pathway do not influence the RRF-induced relaxation and the RRF-induced relaxation seems to be resistant to oxidative stress. The mechanism responsible for the enhanced RRF-induced relaxation in the presence of flufenamic acid or carbenoxolone remains elusive and the RRF does not show more effectivity on retinal arteries.
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Acknowledgements
The authors would like to thank Lies Vancraeynest and Tom Vanthuyne for the excellent technical assistance. We also thank the slaughterhouse Flanders Meat group in Zele to provide us bovine eyes.
Funding
This work is supported by the Fund of Research in Ophthalmology (FRO).
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Vanden Daele, L., Boydens, C. & Van de Voorde, J. Characterization of the retina-induced relaxation in mice. Graefes Arch Clin Exp Ophthalmol 256, 1905–1912 (2018). https://doi.org/10.1007/s00417-018-4096-4
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DOI: https://doi.org/10.1007/s00417-018-4096-4