Fenestrated subendothelial basement membranes in human retinal capillaries

A correlated TEM and SEM study of human retinal capillaries and their associated basement membranes (BMs) was carried out. Control tissues show that these vessels are comprised of a continuous layer of endothelial cells separated from overlying intramural pericytes by a discontinuous subendothelial BM (EBM) which accommodates endothelial cell-pericyte (periendothelial) junctions. Three types of junctions exist, including: (1) "peg-and-socket" arrangements where cytoplasmic processes of the two cell layers interdigitate; (2) adhering plaques similar to desmosomes; and (3) cell/cell contacts where adjacent cell membranes appear to fuse or remain separated by a approximately 2 nm space. Following detergent solubilization, acellular retinal capillaries maintain their cylindrical histoarchitectures and all BM components are imaged by TEM and SEM. Topographical (SEM) studies of cryofractured samples show EBM surfaces with numerous (approximately 1.5/microns 2) oval fenestrations (100-450 nm diameter) that correlate well with EBM discontinuities occupied by periendothelial junctions in control tissues. It seems possible that these structures may play an important role in diabetic retinal neovascularization where pericytes are known to degenerate selectively. In this condition, preformed EBM deficiencies could facilitate endothelial cell migration and sprout formation, leading ultimately to the sequelae of proliferative diabetic retinopathy.