Computational investigation of blood cell transport in retinal microaneurysms

Abstract

Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). MA leakage or rupture may precipitate local pathology in the surrounding neural retina that impacts visual function. Thrombosis in MAs may affect their turnover time, an indicator associated with visual and anatomic outcomes in the diabetic eyes. In this work, we perform computational modeling of blood flow in microchannels containing various MAs to investigate the pathologies of MAs in DR. The particle-based model employed in this study can explicitly represent red blood cells (RBCs) and platelets as well as their interaction in the blood flow, a process that is very difficult to observe in vivo. Our simulations illustrate that while the main blood flow from the parent vessels can perfuse the entire lumen of MAs with small body-to-neck ratio (BNR), it can only perfuse part of the lumen in MAs with large BNR, particularly at a low hematocrit level, leading to possible hypoxic conditions inside MAs. We also quantify the impacts of the size of MAs, blood flow velocity, hematocrit and RBC stiffness and adhesion on the likelihood of platelets entering MAs as well as their residence time inside, two factors that are thought to be associated with thrombus formation in MAs. Our results show that enlarged MA size, increased blood velocity and hematocrit in the parent vessel of MAs as well as the RBC-RBC adhesion promote the migration of platelets into MAs and also prolong their residence time, thereby increasing the propensity of thrombosis within MAs. Overall, our work suggests that computational simulations using particle-based models can help to understand the microvascular pathology pertaining to MAs in DR and provide insights to stimulate and steer new experimental and computational studies in this area.

Multiphysics and multiscale modeling of microthrombosis in COVID-19

“…However, these models cannot be employed to simulate blood cell suspensions or blood flow due to the high computational cost. On the other hand, highly efficient cellular-level RBC and platelet models developed based on [ 42 ] have been widely used to study multiscale biological phenomenons from single RBC mechanics [ 38 , 43 ] to blood flow dynamics [ 44 , 45 ], but they are lack of the biochemical component to describe the coagulation-induced platelet activation. In this work, we implement a multiphysics and multiscale computational framework based on our previous work [ 46 ] to investigate the impacts of multiple prothrombotic factors, such as stasis, inflammatory responses of endothelial cells, aberrant levels of coagulation factors, involvement of WBCs, on microthrombosis in COVID-19.…”

Advancing treatment of retinal disease through in silico trials

“…Microaneurysms are an early manifestation of DR where the walls of capillaries form outpouchings disrupting blood flow and rendering them susceptible to rupture. We found four studies investigating haemodynamics in reconstructed microaneurysms using computational fluid dynamics models [34,75,168,169]. Bernabeu et al considered the shape of microaneurysms and how this influences haemodynamics, and in particular shear rates, in an attempt to determine predictors of the likelihood of leaking blood clotting [34].…”

Recent Advances in Computational Modeling of Biomechanics and Biorheology of Red Blood Cells in Diabetes

“…The rupture of MAs may lead to in retinal edema or hemorrhage, which can directly affect retinal function. Although microfluidic experiments have been performed to investigate blood cell transport and hemodynamics in the MAs [ 122 ], unfolding some biological processes and testing the associated hypotheses that involve blood cell interactions still requires complementary computational simulations [ 123 ]. For example, the enhanced cell adhesion in diabetic blood could promote RBC aggregation and enlarge the cell-free layer near the vessel walls [ 124 , 125 , 126 ], causing reduced average hematocrit level in the branching vessels.…”