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.
OBJECTIVE
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).


CONCLUSIONS
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.
Department of Ophthalmology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark. linperse@rm.dk.
Line
L
Petersen
Department of Ophthalmology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
Toke
T
Bek
D000328:Adult; D000368:Aged; D001160:Arterioles / Q000000981:diagnostic imaging / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D004008:Diclofenac / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009883:Ophthalmic Solutions; D012039:Regional Blood Flow / Q000502:physiology; D012161:Retinal Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000008:administration & dosage*
D016861:Cyclooxygenase Inhibitors; D009883:Ophthalmic Solutions; D004008:Diclofenac; D019323:omega-N-Methylarginine; D009569:Nitric Oxide
Autoregulation; Cyclo-oxygenase; Diabetic retinopathy; L-NMMA; Nitric oxide