Blood Flow In Retinal Vessels Research Articles

Effects of Intravitreal Ranibizumab Injection on Peripheral Retinal Microcirculation and Cytokines in Branch Retinal Vein Occlusion with Macular Edema.

Background and Objectives: To investigate peripheral blood flow in retinal vessels and vessel diameters after intravitreal ranibizumab injection (IRI) and the relationship between these parameters and cytokines in branch retinal vein occlusion (BRVO) with macular edema. Materials and Methods: We assessed relative flow volume (RFV) and the width of the main and branch retinal arteries and veins in the occluded and non-occluded regions before and after IRI in 37 patients with BRVO and macular edema. Measurements were made using laser speckle flowgraphy (LSFG). When performing IRI, we obtained samples of aqueous humor and analyzed them using the suspension array method to evaluate vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: In both retinal regions, before and after IRI, the RFV in the main artery and vein showed a significant correlation with the summed RFV in the respective branch vessels 1 and 2. In the occluded region, the RFV in the main vein was significantly negatively correlated with MCP-1, PDGF-AA, IL-6, and IL-8; the RFV in branch vein 1 was significantly negatively correlated with PlGF, MCP-1, IL-6, and IL-8; PDGF-AA was significantly negatively correlated with the width of the main and branch veins; and the RFVs of the main artery and vein decreased significantly from before to 1 month after IRI. Conclusions: Contrary to expectations, the study found that anti-VEGF therapy does not affect RFV in arteries and veins in patients with BRVO and macular edema. Furthermore, retinal blood flow is poor in patients with high MCP-1, IL-6, and IL-8. Finally, high PDGF-AA may result in smaller venous diameters and reduced retinal blood flow.

ПОРІВНЯЛЬНА ОЦІНКА НЕЙРОРЕТИНОПРОТЕКТИВНОЇ АКТИВНОСТІ АДЕМОЛУ ОКРЕМО ТА ЗА УМОВИ ЙОГО ПОЄДНАННЯ З МЕКСИДОЛОМ ПРИ ЇХ НАРІЗНОМУ ЗАСТОСУВАННІ В КОМПЛЕКСНІЙ ТЕРАПІЇ ПЕРЕХІДНОЇ ІШЕМІЇ ОКА ЩУРІВ ЗА ЗМІНАМИ МЕТАБОЛІЧНИХ ПРОЦЕСІВ В СІТКІВЦІ

РЕЗЮМЕ. Актуальною задачею сучасної фармакології є розробка препаратів на основі біологічно активних речовин, які можуть стати платформою для створення препаратів із нейроцитопротективною активністю для терапії ішемічних уражень зорового аналізатора.Мета дослідження – вивчити вплив блокатора NMDA-рецепторів адемолу на метаболічні процеси в сітківці у гострий постреперфузійний період як можливий внутрішньоклітинний механізм нейроцитопротективної дії препарату та оцінити його ефективність у поєднанні з мексидолом при їх нарізному застосуванні в комплексній терапії цього стану.Матеріали та методи. Терапевтичне застосування ампульного 1,0 % розчину адемолу здійснювали умовно- ефективною дозою 2 мг/кг внутрішньоочеревинно упродовж першої доби гострого постреперфузійного періоду (накладання та подальше затягування ретробульбарних лігатур до зникнення кровотоку в судинах сітківки тривалістю 1 год) через кожні 12 год. Паралельно проводили комбіноване нарізне послідовне з інтервалом 10 хв уведення адемолу (2 мг/кг) та мексидолу (100 мг/кг) за аналогічною схемою. Останню ін’єкцію виконували за 1 год до завершення експерименту та евтаназії тварин.Результати. Адемол дозою 2 мг/кг має комплексну корегувальну дію на порушені внутрішньоклітинні метаболічні процеси в сітківці щурів, що проявляється ліквідацією енергодефіциту (збереження пулу аденозинтрифосфорної кислоти, порівняно із контрольною патологією, в середньому на рівні 18,2 %), антиоксидативним ефектом (зменшення маркерів перекисного окиснення ліпідів та окисної модифікації білків: рівнів малонового діальдегіду та карбонільних груп протеїнів, у середньому відповідно на 33,1 та 26,9 % при паралельному наростанні активності глутатіонпероксидази на 36,0 %, р<0,05) та модулювальним впливом на обмін монооксиду азоту за рахунок зменшення рівня стабільних метаболітів нітроген монооксиду в середньому на 58,0 %. На тлі нарізного послідовного застосування адемолу (2 мг/кг) і мексидолу (100 мг/кг) у складі комплексної терапії ішемії-реперфузії ока щурів відмічається вірогідне потенціювання та сумація позитивних метаболітотропних явищ.Висновки. Зазначені біохімічні зміни характеризують провідні метаболітотропні внутрішньоклітинні (нерецепторні) механізми нейроретинопротективної дії препарату. Отримані дані обґрунтовують доцільність подальшої доклінічної оцінки ефективності поєднання цих лікарських засобів у складі комплексної терапії даної патології та роблять перспективною можливість створення фіксованої комбінованої фармацевтичної композиції на їх спільній основі.

Measurement of Absolute Blood Flow Velocity and Blood Flow in the Human Retina by Dual-Beam Bidirectional Doppler Fourier-Domain Optical Coherence Tomography

The present experiments were undertaken to evaluate the validity of absolute flow velocity measurements with a dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT) system. The flow velocities of diluted milk through a glass capillary were measured at 30 different preset velocities in the range of 0.9 to 39.3 mm/s by bidirectional Doppler FD-OCT. The flow through the capillary was controlled by two infusion pumps working in different flow ranges and based on different technical principles. In vivo the validity of the method for measuring blood flow in retinal vessels was tested at bifurcations. The continuity equation was verified at 10 retinal venous bifurcations of 10 young healthy subjects (mean age, 29 ± 3 years) by velocity measurements, using dual-beam bidirectional Doppler FD-OCT, and measurements of retinal diameters, using the Dynamic Vessel Analyzer. Flow velocities as measured with bidirectional Doppler FD-OCT in the glass capillary were in good agreement with the preset velocities (r = 0.994, P < 0.001 each). No significant difference was found between flow in the trunk vessels before the bifurcation (11.3 ± 5.2 μL/min) and the sum of flows in the daughter vessels (10.7 ± 4.8 μL/min). A significant association was found between retinal vessel diameters and both retinal blood velocities (r = 0.72, P < 0.001) and retinal blood flow (r = 0.95, P < 0.0001). Dual-beam bidirectional Doppler FD-OCT delivered accurate retinal blood velocity values and, thus, offers high potential for examination of retinal blood flow in ocular disease.

Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy

Neuronal activity leads to arteriole dilation and increased blood flow in retinal vessels. This response, termed functional hyperemia, is diminished in the retinas of diabetic patients, possibly contributing to the development of diabetic retinopathy. The mechanism responsible for this loss is unknown. Here we show that light-evoked arteriole dilation was reduced by 58% in a streptozotocin-induced rat model of type 1 diabetes. Functional hyperemia is believed to be mediated by glial cells and we found that glial-evoked vasodilation was reduced by 60% in diabetic animals. The diabetic retinas showed neither a decrease in the thickness of the retinal layers nor an increase in neuronal loss, although signs of early glial reactivity and an upregulation of inducible nitric oxide synthase (iNOS) were detected. Inhibition of iNOS restored both light- and glial-evoked dilations to control levels. These findings suggest that high NO levels resulting from iNOS upregulation alters glial control of vessel diameter and may underlie the loss of functional hyperemia observed in diabetic retinopathy. Restoring functional hyperemia by iNOS inhibition may limit the progression of retinopathy in diabetic patients.

Imaging retinal blood flow with laser speckle flowmetry

Laser speckle flowmetry (LSF) was initially developed to measure blood flow in the retina. More recently, its primary application has been to image baseline blood flow and activity-dependent changes in blood flow in the brain. We now describe experiments in the rat retina in which LSF was used in conjunction with confocal microscopy to monitor light-evoked changes in blood flow in retinal vessels. This dual imaging technique permitted us to stimulate retinal photoreceptors and measure vessel diameter with confocal microscopy while simultaneously monitoring blood flow with LSF. We found that a flickering light dilated retinal arterioles and evoked increases in retinal blood velocity with similar time courses. In addition, focal light stimulation evoked local increases in blood velocity. The spatial distribution of these increases depended on the location of the stimulus relative to retinal arterioles and venules. The results suggest that capillaries are largely unresponsive to local neuronal activity and that hemodynamic responses are mediated primarily by arterioles. The use of LSF to image retinal blood flow holds promise in elucidating the mechanisms mediating functional hyperemia in the retina and in characterizing changes in blood flow that occur during retinal pathology.

Blood Flow in Retinal Vessels of Normal-tension Glaucoma with or without a History of Optic Disc Hemorrhages

To evaluate blood flow in retinal vessels of normal-tension glaucoma (NTG) with or without a history of optic disc hemorrhages (DH) and compare it with that in non-glaucomatous eyes using scanning laser fluorescein video angiography. We enrolled 14 eyes of 14 NTG patients with a history of DH (DH (+) group), 12 eyes of 12 NTG patients without history of DH (DH (-) group), and 10 eyes from 10 non-glaucomatous patients matched for age, intraocular pressure, and systemic blood pressure. No statistically significant difference was observed between the DH (+) and DH (-) groups of NTG in the global indices of the Humphrey visual field. Fluorescein angiography was performed using a scanning laser ophthalmoscope with an argon blue laser. A series of approximately 100 consecutive video images at 1/2 second intervals from just before the dye appearance in the central retinal artery was loaded into an external personal computer system. Based on this acquired image series, we obtained fluorescein filling curves for 10 x 10 pixel measuring areas placed on each of the superior-temporal and inferior-temporal branch retinal arteries and veins at 1/5 papillary diameter from the disc edge. In each vessel, time to the highest fluorescein intensity (peak time, sec) and the time constant of the filling curve (tau, sec) were obtained. Time difference between the peak times in vein and artery (peak time difference) was also calculated. Statistically significant differences were observed among the three groups in the peak time of inferior-temporal artery and vein, and superior-temporal vein (ANOVA, p < 0.01). Also there were statistically significant differences in the tau of all vessels (ANOVA, p < 0.05). No statistically significant differences were observed in the peak time differences. By multivariate analysis, the DH (+) and DH (-) groups of NTG showed significantly longer peak times and tau s than did the non-glaucomatous eyes (p < 0.05). However, no statistically significant differences were observed in any parameters between the DH (+) and DH (-) groups of NTG. In NTG, dye filling rate in both the central retinal arteries and veins seems to be delayed. However, this delay does not differ between DH (+) and DH (-) groups.

レーザースペックル現象を利用した網膜血管血流測定 (II)

The laser speckle method is studied for evaluating the blood flow in retinal vessels of human subjects on the basis of the photon correlation technique. In order to treat effectively the photon correlation data, we improved the apparatus for signal analyses. The experimental results show that the present method is useful for measuring the temporal fluctuations of retinal blood flows.

レーザースペックル現象を利用した網膜血管血流測定 (I)

A method is studied for measuring the blooflow in retinal vessels using laser speckle phenomena. The intensity fluctuation of speckles scattered from red blood cells in a retinal vessel is detected in the magnified image plane, and analyzed by the photon correlator which gives us the relative velocity of the blood flow. The experiments were performed to evaluate the bloodflow velocity in a glass capillary and in the retinal vessels of a rabbit and human volunteers. The results show that the bloodflow in retinal vessels can be measured by using laser speckles.