Human retinal capillary basement membrane leaflets are morphologically distinct: a correlated TEM and SEM analysis

Because retinal capillaries and their associated basement membranes (BMs) are significantly altered in a number of diseases (most notably diabetic retinopathy), the human retinal microvasculature is of interest to both basic scientists and clinicians. Consequently, numerous TEM studies centered primarily on cellular elements of retinal microvessels have been carried out. Ultrastructural studies emphasizing retinal capillary extracellular matrix (ECM) materials including BMs however, are nearly non-existent. Accordingly, the current correlated TEM/SEM investigation was undertaken. The study shows that retinal capillary walls are comprised of a continuous layer of endothelial cells and a discontinuous layer of intramural pericytes which are in frequent contact. These are underlain and/or surrounded by a retinal capillary BM complex which includes pericytic matrix, fibrillar collagen, and subendothelial, pericytic and Müller cell BM leaflets. Following sequential detergent treatment, all retinal cells are solubilized. Vessel ECM components, however, maintain their in vivo histoarchitectural relationships. Moreover, on the basis of substructure, susceptibility to non-specific proteases and anionic site density, BM leaflets are morphologically distinct. In addition, high-resolution SEM studies show that BM surface characteristics are tissue specific. It is concluded that retinal capillary BM complexes are comprised of structurally unique subcomponents the characteristics of which should be considered in future studies of retinal capillary BM structure, composition and function and particularly in investigations in which retinal capillaries are pathologically altered.