Impaired Efferocytosis of Pericytes and Vascular Smooth Muscle Cells in Diabetic Retinopathy
Tom A Gardiner1, Karis Little2, Alan W Stitt2
1School of Medicine, Dentistry & Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, UK.
Abstract:
During diabetic retinopathy (DR), cell death has been characterized in all of the major retinal cell types, but was observed initially in the microvasculature, particularly the mural cells: pericytes and vascular smooth muscle cells (VSMCs). Indeed, our ability to identify the mural cell corpses called "ghost cells" within the vascular basement membranes (BMs) in eyes of diabetic patients and animal models is indicative that removal of dead cells, or efferocytosis (EF), is dysfunctional during this disease. EF is the process whereby apoptotic cells are eliminated through phagocytic engulfment and digestion and is essential to maintain tissue integrity and immune homeostasis. The process occurs in three distinct phases: finding and recognition, engulfment, and digestion, under the direction of "find me" and "eat me" signals and a large array of their cognate receptors and bridging molecules. Efferocytosis can be performed by many cell types, but most efficiently by professional phagocytes, and with such rapidity that the process is extremely difficult to detect in healthy tissues. As delayed EF is a recognized cause of autoimmune and inflammatory disease, mural cell death in DR may create inflammatory foci in the neurovascular unit (NVU). Here we discuss the basic mechanisms of EF in the context of DR and the impact of diabetic metainflammation on EF effector cell dysfunction.
Insights
Diabetic retinopathy (DR) shows dysfunctional efferocytosis (EF), the process of clearing dead cells. This impairs tissue repair and may cause inflammation in the eye's neurovascular unit.
Area of Science:
- Ophthalmology
- Cell Biology
- Immunology
Background:
- Diabetic retinopathy (DR) involves cell death in retinal cells, initially noted in microvasculature mural cells (pericytes and VSMCs).
- Mural cell corpses ('ghost cells') found in diabetic eyes suggest impaired efferocytosis (EF), the clearance of apoptotic cells.
- Dysfunctional EF is linked to autoimmune and inflammatory diseases, potentially creating inflammatory foci in the neurovascular unit (NVU) during DR.
Purpose of the Study:
- To discuss the fundamental mechanisms of efferocytosis (EF) in the context of diabetic retinopathy (DR).
- To explore the impact of diabetic metainflammation on the dysfunction of EF effector cells.
Main Methods:
- Review of existing literature on efferocytosis (EF) mechanisms.
- Analysis of cell death pathways and immune responses in diabetic retinopathy (DR).
- Discussion of the role of metainflammation in modulating EF effector cell function.
Main Results:
- Efferocytosis (EF), crucial for tissue homeostasis, appears dysfunctional in diabetic retinopathy (DR).
- Delayed clearance of dead mural cells in DR may lead to inflammatory responses within the neurovascular unit (NVU).
- Diabetic metainflammation may contribute to the impaired function of cells responsible for efferocytosis (EF).
Conclusions:
- Dysfunctional efferocytosis (EF) is a key feature of diabetic retinopathy (DR), contributing to pathology.
- Targeting EF pathways could offer therapeutic strategies for managing DR and its associated inflammation.
- Understanding the interplay between metainflammation and EF is vital for advancing DR treatment.
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