Retinal capillary pericyte apoptosis in early human diabetic retinopathy

Objective To investigate the nature of retinal capillary pericyte dropout in early human diabetic retinopathy. Methods In the present study, neural retinas of 12 postmortem eyes from 6 patients (3 diabetic and 3 nondiabetic) were first fixed in buffered formaldehyde and then digested with trypsin. The preparations of trypsin-digested retinal blood vessels were stained with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique and then with perdiodic acid-Schiff technique (PAS), and counter-stained with hematoxylin to evaluate DNA fragmentation of cell nuclei and diabetic changes of retinal capillaries. Results TUNEL-positive apoptotic pericytes were observed in retinal capillaries in all three diabetic patients in this study. The TUNEL-positive pericytes were presented as darker stained cells with PAS-hematoxylin staining. A few TUNEL positive retinal capillary endothelial cells were discovered in both eyes of one of the three diabetic patients. Neither TUNEL-positive pericytes nor positive endothelial cells were found in the three nondiabetic patients. A variety of typical diabetic microvascular changes were noticeable with PAS-hematoxylin staining in trypsin-digested retinal preparations from diabetic patients. These changes included thickened capillary walls, microaneurysms, ''ghost-cell''-appearance of pericytes, acellular segments of capillaries, and a decreased ratio of retinal capillary pericytes to endothelial cells. All of these changes are characteristics of diabetic retinal microangiopathy. Conclusions Retinal capillary pericyte apoptosis is a specific form of cell death which occurs during the early development of diabetic retinopathy. The significant decrease in the ratio of pericytes to endothelial cells and the predominant TUNEL-positive pericytes over endothelial cells suggest that a greater impact of apoptosis-related mechanisms occurs in pericytes than in endothelial cells and, thereby, a greater loss of pericytes takes place in early diabetic retinopathy. Apoptosis, therefore, is an important mechanism of pericyte dropout in the early diabetic retinopathy.