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.
Highlights
Microaneurysm (MAs) are one of the earliest clinical signs detected by the routine fundus examination for diabetic retinopathy (DR) [1], the most common microvascular complication of diabetes
Our results show that enlarged MA size, increased blood velocity and hematocrit in the parent vessel of MAs as well as the RBCRBC adhesion promote the migration of platelets into MAs, thereby increasing the propensity of thrombosis within MAs
We quantify the impacts of the size of MAs, blood flow velocity, the hematocrit levels and the biomechanics of red blood cells (RBCs) on the dynamics of platelets inside the MA to explore how these factors contribute to the high propensity of thrombosis in saccular-shaped MAs
Summary
Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). We perform computational modeling of blood flow in microchannels containing various MAs to investigate the pathologies of MAs in DR. Our simulations illustrate that while the main blood flow from the parent vessels can perfuse the entire lumen of small MAs, it can only perfuse part of the lumen in large MAs. Our results show that enlarged MA size, increased blood velocity and hematocrit in the parent vessel of MAs as well as the RBCRBC adhesion promote the migration of platelets into MAs, 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
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