Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects

Dorner, Guido T.; Garhöfer, Gerhard; Huemer, Karl-Heinz; Riva, Charles E.; Wolzt, Michael; Schmetterer, Leopold

doi:10.1016/s0042-6989(03)00170-6

Cited by 73 publications

(47 citation statements)

References 19 publications

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“…36 In contrast, we did not find a correlation of vasodilatation or changes in SO 2 and blood glucose concentration. Whereas Dorner et al increased blood glucose in an interventional study up to the 3-fold of normoglycemia using hyperglycemic insulin clamps, 36 glucose concentration was relatively well controlled in our patients (mean 10.4 mmol/mL postprandially). This might be the reason for the independence of vessel parameters and blood glucose in our measurements.…”

Section: Discussioncontrasting

confidence: 85%

Retinal Vessel Oxygen Saturation under Flicker Light Stimulation in Patients with Nonproliferative Diabetic Retinopathy

Hammer

Heller

Jentsch

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We investigated the response of retinal vessel diameters and oxygen saturation to flicker light stimulation of neuronal activity in patients with diabetic retinopathy. METHODS.We included 18 patients with nonproliferative diabetic retinopathy (mean age 62.2 6 8.3 years, diabetes type 1 in 4 patients and type 2 in 14, hemoglobin A1c 7.7 6 0.9%, duration of diabetes 24.1 6 9.3 years) and 20 agematched healthy controls (age 66.7 6 10.3 years). Dual wavelength (548 and 610 nm) fundus images were taken before and during luminance flicker stimulation (12.5 Hz, modulation depth > 1:25) for 90 seconds. Diameters (central retinal arterial [CRAE] and venous [CRVE] equivalents) and oxygen saturation (SO 2 ) were determined, and averaged for all arterioles and venules in an annular area centered at the optic disk.RESULTS. Flicker light increased CRAE, CRVE, and venous SO 2 by 0.6 6 6.6%, 2.7 6 6.1%, and 2.0 6 2.4% (P < 0.05), respectively, in the patients as well as 4.7 6 8.4% (P < 0.05), 8.7 6 5.2% (P < 0.05), and 4.2 6 3.5% (P < 0.05), respectively, in the controls. The arterial SO 2 remained unchanged in both groups. The increase of the venous SO2 correlated significantly (P ¼ 0.027) with that of the CRAE. There was a trend (P ¼ 0.06) for lower increase of the venous SO 2 with higher body mass index. CONCLUSIONS.Our results support the thesis of an impaired regulation of oxygen supply to the diabetic retina. Whereas in healthy subjects the stimulation of neuronal activity increases the vascular diameters and, subsequently, the oxygen supply, this increase is reduced in diabetic retinopathy. This may hint at the role of endothelial dysfunction in the etiology of the disease. (Invest Ophthalmol Vis Sci.

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Section: Discussioncontrasting

confidence: 85%

Retinal Vessel Oxygen Saturation under Flicker Light Stimulation in Patients with Nonproliferative Diabetic Retinopathy

Hammer

Heller

Jentsch

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…The debate remains as to whether diabetic retinopathy is strictly a vascular disease, as clinically assessed, or a combination of neuronal and vascular changes. 10,11,69 It is unknown whether neuronal or vascular changes precede the other in the setting of diabetes, if hyperglycemia affects one more than the other, or if neurovascular coupling defects [90][91][92] underlie diabetic retinopathy, in whole or in part. While ERGs reflect neuronal responses, our results do not exclude the possibility that vascular changes could underlie or exacerbate neuronal dysfunction.…”

Section: Contribution Of Vascular Pathology To Rodpathway Dysfunctionmentioning

confidence: 99%

Rodent Hyperglycemia-Induced Inner Retinal Deficits are Mirrored in Human Diabetes

Pardue

Barnes

Kim

et al. 2014

Trans. Vis. Sci. Tech.

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Citation: Pardue MT, Barnes CS, Kim MK, et al. Rodent hyperglycemiainduced inner retinal defects are mirrored in human diabetes. Tran Vis Sci Tech. 2014;3(3):6, http:// tvstjournal.org/doi/full/10. 1167/tvst. 3.3.6, doi:10.1167/tvst.3.3.6 Purpose: To evaluate the utility of low luminance stimuli to functionally probe inner retinal rod pathways in the context of diabetes mellitus in both rat and human subjects.Methods: Inner retinal dysfunction was assessed using oscillatory potential (OP) delays in diabetic rats. Scotopic electroretinograms (ERGs) in response to a series of increasing flash luminances were recorded from streptozotocin (STZ)-treated and control Sprague-Dawley rats after 7, 14, 20, and 29 weeks of hyperglycemia. We then evaluated OP delays in human diabetic subjects with (DR) and without (DM) diabetic retinopathy using the International Society for Clinical Electrophysiology in Vision (ISCEV) standard scotopic protocol and two additional dim test flashes.Results: Beginning 7 weeks after STZ, OP implicit times in diabetic rats were progressively delayed in response to dim, but not bright stimuli. In many diabetic subjects the standard ISCEV dim flash failed to illicit measureable OPs. However, OPs became measurable using a brighter, nonstandard dim flash (Test Flash 1, À1.43 log cd s/m 2 ), and exhibited prolonged implicit times in the DM group compared with control subjects (CTRL).Conclusions: Delays in scotopic OP implicit times are an early response to hyperglycemia in diabetic rats. A similar, inner retinal, rod-driven response was detected in diabetic human subjects without diabetic retinopathy, only when a nonstandard ISCEV flash intensity was employed during ERG testing.Translational Relevance: The addition of a dim stimulus to standard ISCEV flashes with assessment of OP latency during ERG testing may provide a detection method for early retinal dysfunction in diabetic patients.

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“…(Increased retinal blood flow in response to dark adaptation is impaired in diabetic rats [51]. In normal human subjects, acute hyperglycemia impairs dilation of retinal vessels in response to flicker photostimulation [52]. )…”

Section: Different Mechanisms Mediate Increases In Nadhc and Glycolysmentioning

confidence: 99%

Interactions Between Hyperglycemia and Hypoxia

et al. 2004

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The primary aim of these experiments was to assess in vitro effects of hyperglycemia (30 mmol/l glucose) and hypoxia (PO 2 ‫؍‬ 36 torr) of 2-h duration, separately and in combination, on cytosolic and mitochondrial free NADH (NADHc and NADHm, respectively) in retinas from normal rats. NADH is the major carrier of electrons and protons that fuel ATP synthesis and several metabolic pathways linked to diabetic complications. T he importance of duration and severity of hyperglycemia in the development of diabetic retinopathy was clearly established by the Diabetes Control and Complications Trial (1); however, the mechanisms that mediate early and late retinal vascular dysfunction and structural changes remain unclear.Proliferative retinopathy is widely attributed to increased production of vascular endothelial growth factor evoked by hypoxia/ischemia caused by capillary closure and nonperfusion that develop relatively early after the onset of diabetes (2).The possibility that hyperglycemia and hypoxia may interact via a common metabolic imbalance(s) to initiate and/or exacerbate complications of diabetes is suggested by the correspondence of several redox, metabolic, and pathophysiological changes evoked by either condition alone. Examples include an increased ratio of reduced to oxidized free cytosolic NADc (3-16), increased production of free radicals (3,17-24) and vascular endothelial growth factor (17,19,(25)(26)(27)(28), accumulation of triose phosphates (7,9,10,13-15), activation of protein kinase C (PKC) (22,28 -30), decreased Na ϩ /K ϩ -ATPase activity (3,30 -33), early increases in blood flow (3,(33)(34)(35), and paradoxical protective effects of diabetes and brief periods of hypoxia/ ischemia (i.e., ischemic preconditioning) that attenuate dysfunction/injury evoked by subsequent more severe hypoxia/ischemia (3,29,36 -38).An increase in free NADH/NAD ϩ c appears to be the best candidate metabolic imbalance for mediating pathophysiological changes common to diabetes and hypoxia (3,38). This redox imbalance develops when electrons and protons are transferred to free oxidized NAD ϩ c (reducing it to NADHc) faster than electrons and protons carried by NADHc are used for ATP synthesis in mitochondria by oxidative phosphorylation. Hypoxia increases free NADHc because lack of O 2 impairs utilization of electrons and protons carried by mitochondrial NADHm for oxidative phosphorylation. The mass action effect of electrons and protons accumulating in NADHm restrains transfer of electrons and protons from free NADHc to NAD ϩ m by the malate-aspartate electron shuttle; thus, electrons and protons accumulate in, and elevate, free NADHc.In cells for which glucose uptake is insulin-independent, hyperglycemia augments glucose uptake and metabolism via the sorbitol pathway. In the second step of the pathway, sorbitol is oxidized to fructose by sorbitol dehydrogenase, which catalyzes transfer of a hydride ion (:H Ϫ ) from sorbitol to free NAD ϩ c (reducing it to NADHc) and removal of a second hydrogen atom that is released i...

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Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects

Cited by 73 publications

References 19 publications

Retinal Vessel Oxygen Saturation under Flicker Light Stimulation in Patients with Nonproliferative Diabetic Retinopathy

Retinal Vessel Oxygen Saturation under Flicker Light Stimulation in Patients with Nonproliferative Diabetic Retinopathy

Rodent Hyperglycemia-Induced Inner Retinal Deficits are Mirrored in Human Diabetes

Interactions Between Hyperglycemia and Hypoxia

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