RETINAL CAPILLARY PERICYTE APOPTOSIS IN EARLY HUMAN DIABETIC-RETINOPATHY

Objective To investigate the nature of retinal capillary pericyte drop out 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 dige sted with trypsin. The preparations of trypsin-digested retinal blood vessels were stained with terminal deoxynucleotidyl transferase-mediat ed dUTP nick end labeling (TUNEL) technique and then with perdiodic ac id-Schiff technique (PAS), and counter-stained with hematoxylin to eva luate 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 wi th PAS-hematoxylin staining. A few TUNEL positive retinal capillary en dothelial cells were discovered in both eyes of one of the three diabe tic patients. Neither TUNEL-positive pericytes nor positive endothelia l cells were found in the three nondiabetic patients. A variety of typ ical diabetic microvascular changes were noticeable with PAS-hematoxyl in staining in trypsin-digested retinal preparations from diabetic pat ients. These changes included thickened capillary walls, microaneurysm s, ''ghost-cell''-appearance of pericytes, acellular segments of capil laries, and a decreased ratio of retinal capillary pericytes to endoth elial cells. All of these changes are characteristics of diabetic reti nal microangiopathy. Conclusions Retinal capillary pericyte apoptosis is a specific form of cell death which occurs during the early develop ment of diabetic retinopathy. The significant decrease in the ratio of pericytes to endothelial cells and the predominant TUNEL-positive per icytes over endothelial cells suggest that a greater impact of apoptos is-related mechanisms occurs in pericytes than in endothelial cells an d, thereby, a greater loss of pericytes takes place in early diabetic retinopathy. Apoptosis, therefore, is an important mechanism of pericy te dropout in the early diabetic retinopathy.