Neurovascular Dysfunction Precedes Neural Dysfunction in the Retina of Patients with Type 1 Diabetes

Lasta, Michael; Pemp, Berthold; Schmidl, Doreen; Boltz, Agnes; Kaya, Semira; Palkovits, Stefan; Werkmeister, René M.; Howorka, Kinga; Popa-Cherecheanu, Alina; Garhöfer, Gerhard; Schmetterer, Leopold

doi:10.1167/iovs.12-10873

Cited by 82 publications

(67 citation statements)

References 46 publications

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“…As glial cells and neurons are also capable of generating NO by the neuronal isoform of NO synthase (NOS) [23], the response of retinal vessels to flicker-light may be determined by both intact vascular endothelium and intact neuron-to-glial signalling. Recent findings suggest that the reduced retinal flicker response in early diabetes mellitus is a consequence of altered endothelial function rather than impaired neural activity [20]. Applied to our results, we conclude that early insulin resistance is associated with undisturbed retinal endothelial function.…”

Section: Discussionsupporting

confidence: 79%

“…Potassium and nitric oxide (NO) appear to be putative mediators of the hyperaemic response to flicker-light in healthy humans [19,20] although this concept has previously been challenged by animal data [21]. Recent evidence in humans, however, renders a proposed role of epoxyeicosatrienoic acids and prostaglandins in vasodilation induced by flicker-light unlikely [22].…”

Section: Discussionmentioning

confidence: 99%

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Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals

Reimann

Vilser²,

Grüber

et al. 2015

Diabetologia

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Aims/hypothesis Insulin may link metabolic disorders to retinal microvascular pathology. The aim of the present study was to investigate the impact of early insulin resistance on retinal microcirculation. Methods Retinal diameter responses to flicker-light stimulation were investigated in 81 clinically healthy participants (32 ±6 years [mean±SD], 59% women) who were recruited according to their BMI. All participants underwent an OGTT and euglycaemic-hyperinsulinaemic clamp (40 mU/m 2 · min −1 insulin dose). After stratification by low and high insulin sensitivity based on a clamp-derived glucose disposal rate of ≤ or >4.9 mg/kg body mass, respectively, baseline retinal diameters and their relative changes to flicker stimulation were compared while controlling for mean arterial pressure, BMI and sex.Results The arterial vasodilator response at the end of flicker stimulation (p=0.044) and the area under the arterial reaction curve during flicker stimulation (p=0.015) were significantly higher in individuals with low vs high insulin sensitivity. Vasodilatory responses of retinal veins to flicker stimulation and baseline retinal diameters did not differ between insulinsensitive and insulin-resistant participants (p>0.05). In a stepwise linear regression analysis, fasting insulin remained the only predictor of the arterial vasodilator response to flicker-light (p<0.01). Waist circumference also contributed, although to a lesser extent, to the arterial vasodilator response (p=0.023). Conclusions/interpretation Insulin sensitivity is an important determinant of retinal microvascular function. We propose that the elevated arterial flicker response in insulin-resistant states is a result of higher circulating insulin levels.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals

Reimann

Vilser²,

Grüber

et al. 2015

Diabetologia

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“…58 A reduction in the retinal response to flicker stimulation can be seen in diabetic patients before any change in pattern electro-retinography becomes evident. 59 In diabetic rats, the abnormal retinal flicker response can be normalized by inhibition of inducible nitric oxide synthase. 56 In conclusion, we presented a method for measuring relative changes in retinal blood flow by combining the Doppler OCT technique with fundus camera-based measurement of retinal vessel diameters.…”

Section: Discussionmentioning

confidence: 99%

Measurement of retinal blood flow in the rat by combining Doppler Fourier-domain optical coherence tomography with fundus imaging

et al. 2014

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Abstract. A wide variety of ocular diseases are associated with abnormalities in ocular circulation. As such, there is considerable interest in techniques for quantifying retinal blood flow, among which Doppler optical coherence tomography (OCT) may be the most promising. We present an approach to measure retinal blood flow in the rat using a new optical system that combines the measurement of blood flow velocities via Doppler Fourier-domain optical coherence tomography and the measurement of vessel diameters using a fundus camera-based technique. Relying on fundus images for extraction of retinal vessel diameters instead of OCT images improves the reliability of the technique. The system was operated with an 841-nm superluminescent diode and a charge-coupled device camera that could be operated at a line rate of 20 kHz. We show that the system is capable of quantifying the response of 100% oxygen breathing on the retinal blood flow. In six rats, we observed a decrease in retinal vessel diameters of 13.2% and a decrease in retinal blood velocity of 42.6%, leading to a decrease in retinal blood flow of 56.7%. Furthermore, in four rats, the response of retinal blood flow during stimulation with diffuse flicker light was assessed. Retinal vessel diameter and blood velocity increased by 3.4% and 28.1%, respectively, leading to a relative increase in blood flow of 36.2%. The presented technique shows much promise to quantify early changes in retinal blood flow during provocation with various stimuli in rodent models of ocular diseases in rats. © 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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“…Відомо, що нейродегенерація є ранньою лан-кою патогенезу діабетичної ретинопатії, яка пе-редує проявам судинних ускладнень (мікро-ангіопатії) [4,8]. Локальні ушкодження сітківки при ЛК можуть розповсюджуватися та призводи-ти до прогресування морфологічнх та функціона-льних змін сітківки.…”

Section: буковинський медичний вісникunclassified

“…Застосування лазеркоагуля-ції (ЛК) сітківки стало вагомим проривом у ліку-ванні ДР [1]. Існують дані, що ЦД зумовлює поя-ву дефектів або зменшення товщини шару нерво-вих волокон сітківки з першої стадії діабетичної васкулопатії [4, 5,8], а діабетичну ретинопатію сьогодні розглядають як нейроваскулярне ускла-днення ЦД або сенсорну нейропатію [3,5,10]. Лазеркоагуляція сітківки, яка є стандартним ліку-ванням при ДР, має певний негативний вплив на шари сітківки та може призвести до ушкодження гангліонарних клітин та втрати шару нервових клітин у сітківці з подальшим потоншенням пе-рипапілярних нервових волокон.…”

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Efficacy of Neuroprotective Support of the Patients With Diabetes Mellitus During Panretinal Laser Photocoagulation

Karliychuk¹

2017

Buk. Med. Herald

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М.А. Карлійчук ЕФЕКТИВНІСТЬ НЕЙРОПРОТЕКТОРНОГО СУПРОВОДУ ХВОРИХ НА ЦУКРОВИЙ ДІАБЕТ ПРИ ВИКОНАННІ ПАНРЕТИНАЛЬНОЇ ЛАЗЕРКОАГУЛЯЦІЇВищий державний навчальний заклад України «Буковинський державний медичний університет», м. ЧернівціРезюме. Мета дослідження полягала в оцінці впливу цитиколіну на морфометричні та функціональні параметри сітківки у хворих на цукровий діабет 2-го типу при виконанні панретинальної лазеркоагуляції. Нами обстежено 47 пацієнтів (79 очей) з препроліфера-тивною діабетичною ретинопатією, яким була виконана панретинальна лазеркоагуляція за три сеанси. 28 паціє-нтів (43 ока) основної групи отримували цитиколін упродовж двох місяців після першого сеансу лазеркоа-гуляції. Критеріями ефективності були зміни гостроти зору від вихідного рівня, товщина шару нервових воло-кон сітківки та порогова ретинальна світлочутливість до та через один, три та шість місяців після лазеркоагу-ляції. Отримані нами результати свідчать про позитив-ний вплив цитиколіну на шар ретинальних нервових волокон при виконанні лазеркоагуляції сітківки, що дозволяє рекомендувати його як медикаментозний су-провід панретинальної лазеркоагуляції у хворих на цукровий діабет 2-го типу.Ключові слова: цукровий діабет, панретинальна лазеркоагуляція, діабетична ретинопатія, нейропротек-ція.

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Neurovascular Dysfunction Precedes Neural Dysfunction in the Retina of Patients with Type 1 Diabetes

Abstract: The study confirms that flicker responses are reduced early in patients with type 1 diabetes. This is seen before alterations in pattern ERG indicating abnormal neurovascular coupling.

Cited by 82 publications

References 46 publications

Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals

Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals

Measurement of retinal blood flow in the rat by combining Doppler Fourier-domain optical coherence tomography with fundus imaging

Efficacy of Neuroprotective Support of the Patients With Diabetes Mellitus During Panretinal Laser Photocoagulation

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