Peter Friis Jeppesen

Use of the retinal vessel analyzer in ocular blood flow research

Acta Ophthalmol. 2010: 88: 717–722

The age-dependent decrease in the myogenic response of retinal arterioles as studied with the Retinal Vessel Analyzer.

PurposeTo study the age-dependent change in myogenic response of retinal arterioles.MethodsFifty-one healthy volunteers with at least ten persons in each of the five age decades (I–V) between 20 and 69 years were subjected to diameter measurement of retinal arterioles using the Retinal Vessel Analyzer (RVA) during rest and during an increase in the systemic blood pressure when lifting hand weights. The transmural pressure in the retinal arterioles during the procedures was estimated from the blood pressure and the intraocular pressure and was compared to the accompanying diameter response.ResultsThe retinal arteriolar diameter showed a significant decrease as a function of increasing weight for the two younger age groups below the age of 40 years (P=0.007, group I, and P=0.049, group II), compatible with perfect autoregulation, whereas no such change was observed in persons above this age (P=0.41, 0.053, 0.29 for groups III–V, respectively).ConclusionStudies on autoregulation in retinal disease should consider the normal age-related decrease in diameter response of retinal arterioles when the blood pressure is changed.

Myogenic response in isolated porcine retinal arterioles

Purpose. To study the myogenic response in large and small porcine retinal arterioles and the effects of blockade of L-type voltage gated calcium channels on the myogenic response. Methods. Eleven large (outer diameter 137.7 ± 4.5 µm) and fourteen small (77.3 ± 3.7 µm) isolated porcine retinal arterioles were studied for myogenic response while mounted between two double-barrelled pipette systems. The intraluminal pressure was varied from 0 to 140 cm H 2 O (0-103 mmHg) and the diameter changes of the arterioles were registered. The pressure-diameter relation was determined for arterioles in calcium-containing and calcium free solutions and during inhibition of the L-type voltage gated calcium channels with nifedipine. Results. Both large and small retinal arterioles showed a decrease in diameter as the intraluminal pressure was increased, but no significant difference was found between large and small arterioles (p = 0.39). Blockade of voltage gated calcium channels significantly abolished the myogenic response (p = 0.010 and p = 0.005, large and small arterioles respectively). Conclusions. The results indicate that myogenic responses are present throughout the retinal arteriolar system and that L-type voltage gated calcium channels are involved in transforming the stretch of retinal vascular smooth muscle cells induced by an increase in intraluminal pressure into a contraction.

Differential diameter responses in macular and peripheral retinal arterioles may contribute to the regional distribution of diabetic retinopathy lesions

BackgroundDiabetic retinopathy is assumed to be due to impaired retinal autoregulation, involving both pressure autoregulation and metabolic autoregulation. The disease displays regional differences, with signs of hyperperfusion in the macular area and capillary occlusion with retinal ischemia in the peripheral retinal areas. It can be hypothesized that these regional differences in the occurrence of retinopathy lesions may reflect differences in the capacity of retinal arterioles to autoregulate the diameter of retinal arterioles.MethodsSeventeen normal persons and two matched groups of patients with respectively diabetic maculopathy and proliferative diabetic retinopathy were examined. The diameter change of a macular and a peripheral retinal arteriole during an increase in the arterial blood pressure induced by isometric exercise, during an increase in retinal metabolism induced by flicker stimulation, and during both stimulus paradigms simultaneously were studied using the dynamic vessel analyzer (DVA).ResultsDuring isometric exercise, the diameter response was reduced in both macular and peripheral retinal arterioles in the two groups of patients with diabetes mellitus. During flicker stimulation, the diameter response was significantly reduced in patients with proliferative diabetic retinopathy, but there was no significant difference between the responses of macular and peripheral arterioles. During simultaneous isometric exercise and flicker stimulation, there was no difference between the diameter response of macular arterioles in the three groups, whereas the diameter response of macular arterioles was significantly lower in normal persons and significantly higher in persons with proliferative diabetic retinopathy as compared to peripheral arterioles.ConclusionsRegional differences in the disturbances of the diameter response to increased blood pressure may contribute to the regional differences in the distribution of diabetic retinopathy lesions. In the central retinal areas, the diameter response to increased blood pressure and retinal metabolism interacted in a way that may potentially protect this area from ischaemia, whereas this protective mechanism was absent in the peripheral retinal arterioles. An elucidation of the mechanisms underlying diameter regulation to increased blood pressure and retinal metabolism, and the interaction between these two mechanisms, may help in understanding the pathophysiology of diabetic retinopathy.

Adenosine relaxation in small retinal arterioles requires functional Na-K pumps and KATP channels

Purpose. To study the effect of Na-K pump and K ATP channel inhibition on the diameter and the adenosine-induced vasodilation of small retinal arterioles. Methods. Thirty isolated porcine arterioles with a diameter of approximately 70 µm were mounted in a double-barrelled pipette system placed in an organ bath, and diameter changes were studied under isobaric no-flow conditions. After an equilibration period, the arterioles were incubated with the Na-K pump inhibitors ouabain and low K + medium or the K ATP channel inhibitor glibenclamide, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted and the adenosine concentration response curve was measured with and without the presence of inhibitors. Results. Inhibition of the Na-K pump elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.047), whereas no change in the spontaneous diameter was induced by inhibition of the K ATP channels (P = 0.754). Inhibition of the Na-K pump with ouabain or with low K + medium, as well as inhibition of the K ATP channels with glibenclamide, both diminished the adenosine induced vasodilation (P = 0.003, P = 0.01, and P = 0.003, respectively). Conclusion. The adenosine-induced vasodilation of small retinal arterioles involves the K ATP channels and the Na-Kpump. Changes in the metabolism of adenosine as well as the activity of the K ATP channels or the Na-K pump can be expected to influence the retinal blood flow.