Defective Myogenic Response to Posture Change in Retinal Vessels of Well-Controlled Type 1 Diabetic Patients with No Retinopathy

Abstract

PURPOSE. The current approach to the prevention of diabetic retinopathy relies on intensive anti-diabetes treatment and is only partially successful. A marker of retinopathy risk would enable strategies of surveillance, screening of adjunct drugs, and targeted drug interventions. The authors sought to identify early abnormalities of retinal vessels that are not prevented by the current therapeutic approach. METHODS. Retinal thickness (an informer of vascular permeability) and hemodynamic parameters at baseline and longitudinally were measured in 27 subjects (age, 32 Ϯ 9 years [mean Ϯ SD]) with well-controlled type 1 diabetes of 12.4 Ϯ 6.4 years' duration and no retinopathy, and in 27 control subjects. In a subset of 17 patients and 11 controls, the hemodynamic response to reclining, a postural change that increases retinal perfusion pressure, was measured. RESULTS. Baseline foveal thickness and hemodynamic parameters were similar in the diabetic and control subjects. Foveal thickness increased over 12 months in the diabetic subjects, from 217 Ϯ 22 m to 222 Ϯ 20 m (P ϭ 0.0036), remaining however within the normal range. Reclining uncovered in 47% of diabetic subjects (P ϭ 0.016 compared with controls) an absent myogenic response (i.e., unchanged or increased arterial diameter instead of the normal decrease). The patterns were repeatable. Only the diabetic group with defective vasoconstriction showed widening arterial diameter over 12 months, a change presaging vascular dilatation in diabetic retinopathy. CONCLUSIONS. Defective myogenic response to pressure was the first detectable abnormality of retinal vessels in subjects with well-controlled type 1 diabetes. Because of its selective occurrence, interpretability in individual patients, and pathogenic potential, the abnormality deserves evaluation as a risk marker for retinopathy. (

Impaired Myogenic Tone in Isolated Cerebral and Coronary Resistance Arteries from the Goto-Kakizaki Rat Model of Type 2 Diabetes

“…The reduced myogenic tone in cerebral and coronary arteries from GK rats found in this study is in accordance with, and further extends, previous studies showing decreased myogenic tone in cerebral arteries from 18-week-old GK rats [17] and from human retinal and subcutaneous arteries [11,30], but contradicts results on cerebral arteries from rats with streptozotocin-induced diabetes showing increased myogenic tone [25]. As there was no difference in response between arteries (both cerebral and coronary) from GK and CW rats to full depolarization with 125 m M K + -PSS, it was apparent that the difference in development of myogenic tone was not due to a defective contractile apparatus.…”

“…This response plays a central role in the autoregulation of blood flow and control of capillary pressure [7,8,9] and recent studies have shown that both the structure [10] and myogenic response [11] are altered in resistance arteries from patients with diabetes. The myogenic response is the initial response to a given change in transmural pressure across the arterial wall.…”

MRI of rod cell compartment-specific function in disease and treatment in vivo

“…Example 3: In proliferative and non-proliferative disease, the most commonly detected abnormality across many labs and methods (including MRI) is retinal vessel dysfunction during, for example, a hyperoxic provocation (i.e., a stress test) Lorenzi et al, 2010;Trick and Berkowitz, 2005). Importantly, treatments that correct retinal vessel dysfunction also correct later histopathology Trick and Berkowitz, 2005).…”

Dynamic Responses in Retinal Vessel Caliber With Flicker Light Stimulation and Risk of Diabetic Retinopathy and Its Progression

“…Multiple ways to study these pathways using different methods have been explored. For example, Lorenzi [41][42][43] has shown that abnormal myogenic responses of retinal vessels measured using laser Doppler flowmetry are precursors to clinical DR and may predict accelerated DR development. Other authors have used magnetic resonance imaging to quantify retinal oxygenation and shown it to predict DR risk.…”