title: Leukocytes in diabetic retinopathy.
abstract: Diabetic retinopathy is one of the most common diabetic complications, and is a major cause of new blindness in the working-age population of developed countries. Progression of vascular abnormalities, including the selective loss of pericytes, formation of acellular capillaries, thickening of the basement membrane, and increased vascular permeability characterizes early nonproliferative diabetic retinopathy (NPDR). Capillary occlusion, as shown on fluorescein angiograms, is also one of the earliest clinically recognizable lesion of NPDR. In response to capillary non-perfusion, there is dilation of neighbouring capillaries, leading to early blood-retinal barrier breakdown, capillary non-perfusion, and endothelial cell injury and death. The resulting ischemia leads to increased production of growth factors, and the development of proliferative diabetic retinopathy (PDR), which is characterized by growth of new vessels and potential severe and irreversible visual loss. The exact pathogenic mechanism by which capillary non-perfusion occurs is still unclear but growing evidence now suggests that increased leukocyte-endothelial cell adhesion and entrapment (retinal leukostasis) in retinal capillaries is an early event associated with areas of vascular non-perfusion and the development of diabetic retinopathy. The leukocytes in diabetic patients are less deformable more activated, and demonstrate increased adhesion to the vascular endothelium. This review summarizes the current literature on the role of leukocytes in the pathogenesis of capillary occlusion, and discusses the potential of leukostasis as a new promising target in the treatment of diabetic retinopathy.
authors.affiliation: Cardiovascular Division, GKT School of Biomedical & Health Sciences, King's College London, Guy's Campus, London, UK. rakesh.chibber@kcl.ac.uk
authors.forename: Rakesh
authors.initials: R
authors.lastname: Chibber
authors.forename: Bahaedin M
authors.initials: BM
authors.lastname: Ben-Mahmud
authors.forename: Surina
authors.initials: S
authors.lastname: Chibber
authors.forename: Eva M
authors.initials: EM
authors.lastname: Kohner
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000209:etiology / Q000473:pathology; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000473:pathology; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000473:pathology / Q000502:physiology*; D008954:Models, Biological