Diabetic Retinopathy Is Related to Both Endothelium-Dependent and -Independent Responses of Skin Microvascular Flow

Nguyên, Thành Tâm; Shaw, Jonathan E.; Robinson, Carol V.; Kawasaki, Ryo; Wang, Jie Jin; Kreis, Andreas; Wong, Tien Yin

doi:10.2337/dc10-1985

Cited by 47 publications

(44 citation statements)

References 21 publications

(27 reference statements)

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“…We recruited 224 patients (18-70 years of age) with diabetes (85 with type 1 and 139 with type 2), as previously described [4][5][6][7]. We excluded participants who had a history of epilepsy or glaucoma, had undergone previous vitreal surgery, and/or had a cataract on examination.…”

Section: Study Populationmentioning

confidence: 99%

“…Iontophoresis delivers vasodilators (SNP and ACh) across the skin using a weak electrical current, with blood flow measured by laser Doppler flowmeter (Moor Instruments, Axminster, UK) [5].…”

Section: Study Populationmentioning

confidence: 99%

“…However, whether these novel markers have additional predictive value in DR is uncertain. In previous reports, we have also demonstrated that several novel systemic and retinal risk markers, including serum levels of apolipoprotein (Apo) AI and B [4], skin microvascular responses to sodium nitroprusside (SNP) and acetylcholine (ACh) iontophoresis [5], flicker-light-induced retinal vasodilation [6] and static measurement of retinal arteriolar tortuosity from photographs [7], are independently associated with DR. However, there are no data on whether these novel markers, in isolation or in combination, add to traditional risk factors in predicting DR.…”

Section: Introductionmentioning

confidence: 99%

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Novel versus traditional risk markers for diabetic retinopathy

et al. 2011

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Aims/hypothesis To explore the relative contribution of novel and traditional risk markers for diabetic retinopathy (DR). Methods A clinic-based study of 224 diabetic patients (85 type 1, 139 type 2) from a diabetes clinic was performed. DR was graded from fundus photographs according to the Airlie House Classification system and classified as absent or present (at least ETDRS level 14). Novel risk markers assessed included serum apolipoprotein (Apo) AI and B, skin microvascular responses to acetylcholine (endotheliumdependent) and sodium nitroprusside (endothelium-independent) iontophoresis, flicker-light-induced retinal vasodilation and retinal vascular tortuosity. Relative contribution was determined by semi-partial correlation coefficient generated from a logistic regression model containing all traditional and novel risk markers simultaneously. Results There were 144 (64.3%) participants with DR. Of the novel markers, ApoAI, flicker-light-induced vasodilation and retinal arteriolar tortuosity were significantly associated with DR, independently of traditional measures (all p<0.03). Diabetes duration contributed most (51%) to the risk of DR, followed by ApoAI (16%), systolic blood pressure (13%), retinal arteriolar tortuosity (8%) and flicker-light-induced venular and arteriolar dilation (3% and 0.5%, respectively). Conclusions/interpretation ApoAI and retinal arteriolar tortuosity made considerable contributions to DR risk, independently of traditional risk markers. Findings from this study suggest that serum ApoAI and retinal arteriolar tortuosity may be novel and independent risk markers of DR.

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Section: Study Populationmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel versus traditional risk markers for diabetic retinopathy

et al. 2011

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“…[3][4][5] The abundant vascular network in skin provides an accessible and common vascular bed for assessing vascular hemodynamic response. 6,7 In recent years, the skin vascular function started to draw widespread attention as a potential research biomarker to predict cardiovascular diseases 8 and diabetic retinopathy 9 or as a prognostic marker for evaluating drugs effect on the microcirculation. 10 Previous studies showed diabetes could cause various skin vascular changes, including microvascular structure, 11 vascular density and diameter, 12 blood flow and blood oxygen, 13,14 and vascular permeability.…”

Section: Introductionmentioning

confidence: 99%

Visualization of skin microvascular dysfunction of type 1 diabetic mice using in vivo skin optical clearing method

et al. 2018

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"Visualization of skin microvascular dysfunction of type 1 diabetic mice using in vivo skin optical clearing method," J. Biomed. Opt. 24(3), 031003 (2018), doi: 10.1117/1.JBO.24.3.031003. Abstract. To realize visualization of the skin microvascular dysfunction of type 1 diabetic mice, we combined laser speckle contrast imaging and hyperspectral imaging to simultaneously monitor the noradrenaline (NE)-induced responses of vascular blood flow and blood oxygen with the development of diabetes through optical clearing skin window. The main results showed that venous and arterious blood flow decreased without recovery after injection of NE; furthermore, the decrease of arterious blood oxygen induced by NE greatly weakened, especially for 2-and 4-week diabetic mice. This change in vasoconstricting effect of NE was related to the expression of α1-adrenergic receptor. This study demonstrated that skin microvascular function was a potential research biomarker for early warning in the occurrence and development of diabetes. The in vivo skin optical clearing method provides a feasible solution to realize visualization of cutaneous microvessels for monitoring microvascular reactivity under pathological conditions. In addition, visual monitoring of skin microvascular function response has guiding significance for early diagnosis of diabetes and clinical research. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…[9][10][11][12] Moreover, some clinical studies have reported that vasodilation of the retinal vessels elicited by flicker stimuli deteriorates in patients with these diseases. [13][14][15] However, the involvement of glial cells in regulating the RBF in response to flicker stimulation has not been well determined. 16 Although some reports have focused on the role of glial cells in metabolic autoregulation in neurovascular coupling, 2,6,[16][17][18] the role in the retinal vasculature remains unclear.…”

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confidence: 99%

Role of Glial Cells in Regulating Retinal Blood Flow During Flicker-Induced Hyperemia in Cats

Song

Nagaoka

Yoshioka

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate how glial cells participate in retinal circulation during flicker stimulation in cats.METHODS. Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. Twenty-four hours after intravitreal injections of L-2-aminoadipic acid (LAA), a gliotoxic compound, and the solvent of 0.01 N hydrochloric acid as a control, we examined the changes in RBF in response to 16-Hz flicker stimulation for 3 minutes. We also measured the changes in RBF 2 hours after intravitreal injection of Nx-propyl-L-arginine (L-NPA), a selective neuronal nitric oxide synthase inhibitor, in LAA-treated eyes. To evaluate the effects of LAA on retinal neuronal function, ERGs were monitored. Immunohistochemical examinations were performed.RESULTS. In LAA-treated eyes, histologic changes selectively occurred in retinal glial cells. There were no significant reductions in amplitude or elongation of implicit time in ERG after LAA injections compared with controls. In control eyes, the RBF gradually increased and reached the maximal level (53.5% 6 2.5% increase from baseline) after 2 to 3 minutes of flicker stimulation. In LAA-treated eyes, the increases in RBF during flicker stimulation were attenuated significantly compared with controls. In LAA-treated eyes 2 hours after injection of L-NPA, flicker-evoked increases in RBF decreased significantly compared with LAA-treated eyes. CONCLUSIONS.The current results suggested that increases in RBF in response to flicker stimulation were regulated partly by retinal glial cells.

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Diabetic Retinopathy Is Related to Both Endothelium-Dependent and -Independent Responses of Skin Microvascular Flow

Cited by 47 publications

References 21 publications

Novel versus traditional risk markers for diabetic retinopathy

Novel versus traditional risk markers for diabetic retinopathy

Visualization of skin microvascular dysfunction of type 1 diabetic mice using in vivo skin optical clearing method

Role of Glial Cells in Regulating Retinal Blood Flow During Flicker-Induced Hyperemia in Cats

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