Erythrocyte oxidative stress is associated with cell deformability in patients with retinal vein occlusion

Abstract

Essentials• Retinal vein occlusion (RVO), characterized by blood hyperviscosity, has an unclear pathogenesis.• We aimed to find out if hemorheological profile is altered by oxidative stress in RVO patients.• Red blood cell (RBC) oxidative stress is associated to whole blood viscosity and RBC deformability.• Reactive oxygen species alter RBC membrane rigidity, playing a key role in RVO pathogenesis.Summary. Background: Retinal vein occlusion (RVO) is characterized by vision loss resulting from hypoperfusion and hypoxia of the retina. RVO pathogenesis is not yet fully understood, although blood hyperviscosity has been observed. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to microvascular perfusion and oxygen delivery. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Objectives: To determine whether erythrocytes from RVO patients show signs of oxidative stress, and whether this condition can modify the hemorheologic profile in these patients. Patients and Methods: We analyzed the entire hemorheologic profile and erythrocyte oxidative stress -reactive oxygen species (ROS) production and membrane lipid peroxidation -in 128 RVO patients and 128 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results: In RVO patients, erythrocyte oxidative stress was present and positively correlated with whole blood viscosity and erythrocyte deformability. Multivariate linear regression analysis after adjustment for age, cardiovascular risk factors, medications, leukocyte number and mean corpuscular volume indicated that erythrocyte-derived ROS and erythrocyte lipid peroxidation were significantly and positively correlated with erythrocyte membrane viscosity and deformability. Moreover, in vitro experiments demonstrated that ROS have a key role in erythrocyte membrane fluidity. Conclusions: Our findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of RVO, and pave the way to new therapeutic interventions.

Red blood cells: the forgotten player in hemostasis and thrombosis

“…This review will briefly summarize what is currently known about the involvement of RBCs in hemostasis and thrombosis and its underappreciated importance. RBCs increase blood viscosity because of a rise in hematocrit, an increase in RBC aggregation or a decrease in RBC deformability (increasing flow resistance) Pro [2][3][4][5] Conversely, anemia is associated with low blood viscosity and bleeding tendency as a result of reduced platelet margination toward endothelium and enhanced NO availability Anti [2][3][4][5] RBCs undergo shear-dependent reversible aggregation mediated by plasma proteins (mainly fibrinogen and immunoglobulins) and/or local osmotic gradient Pro [14][15][16][70][71][72][73][74] RBCs with increased rigidity occlude small vessels Pro [11,12] Deformability of RBCs reduces frictional resistance to flow Anti [8,[11][12][13]] RBCs maintain biconcave shape and a high surface-to-volume ratio as a result of cytoskeleton and water/ions balance Pro or anti [5] RBCs migrate to the center of blood flow and push platelets toward the endothelium (margination) in a hematocrit-and shear-dependent manner Pro [59][60][61] Effects on platelet reactivity RBCs increase platelet adhesion and aggregation by release of ADP and thromboxane A 2 Pro [66,67] RBCs form aggregates with platelets via adhesive molecules (ICAM-4 and fibrinogen with aIIbb3)…”

Systemic oxidative stress in congenital central hypoventilation syndrome

“…Cell viability, controlled by flow cytometry with propidium iodide staining, was found to exceed 95%. The erythrocyte ROS production was analysed as previously reported [16]. For a single analysis, the fluorescence signals of 100,000 erythrocytes were collected.…”

Thrombosis Risk in Cancer Patients Receiving Red Blood Cell Transfusions

“…Thirty studies were conducted in specific anatomic categories of surgery. The two largest surgical categories were urologic (13) and abdominal (9). The urologic series had the highest number of positive studies for transfusion and thrombosis, with three MV-positive correlations and three UV-only positive correlations (no MV done), plus Yoo et al 48 who found a positive RBC volume correlation.…”