Purpose
The exact pathogenesis of normal-tension glaucoma is unknown, and evidence shows that the properties of the lamina cribrosa and sclera may play a role. In this study, we investigated the major extracellular matrix (ECM) components of the lamina cribrosa and sclera in human donor eyes to determine the differences between Korean and Caucasian eyes.
Methods
Quantitative RT-PCR was performed with the total RNA extracted from the retina, choroid, sclera, peripapillary sclera (2 mm surrounding the lamina cribrosa), lamina cribrosa, and the optic nerve to quantitatively evaluate the ECM protein composition in ocular tissues. The collagen and elastic fiber systems were analyzed qualitatively and quantitatively in cross-sections of the lamina cribrosa. Collagen fibers stained with picrosirius red and elastic fibers stained with resorcin-fuchsin stain. Indirect immunofluorescence single- or double-labeling was performed on cryosections of posterior segment tissues using primary antibodies against lysly oxidase, lysyl oxidase-like 1, lysly oxidase-like 2, elastin, and fibrillin-1. Ultrathin sections (70-90 nm) were taken from representative areas, placed on copper mesh grids (Electron Microscopy Sciences), and examined using an electron microscope. The stress-stain relationship was measured using the Biomaterial Universal testing machine.
Results
Collagen and elastin were significantly more abundant in Korean eyes as measured by quantitative polymerase chain reaction and immunohistochemical staining. The morphology of the collagen and elastic fibers as visualized by special stains and electron microscopy differed by race. Collagen fibers had a greater preferred directionality and smaller fibril diameter in Korean eyes. Elastic fibers in Korean eyes formed round aggregates around the laminar beams and shorter, ill-defined or coiled-like fibril structures. The mechanical properties of the ONH tissues produced greater strain in Korean eyes.
Conclusions
Therefore, the lamina cribrosa and peripapillary sclera are more easily deformed by similar pressures in Korean eyes compared to Caucasian eyes. Racial differences in the ECM composition and microscopic architecture may contribute to the greater deformation of the ONH tissues under the normal IOP range and the prevalence of NTG in Asian eyes.