The Contribution of Sulfated Glycosaminoglycans to the Inflation Response of the Human Optic Nerve Head.
Midgett Dan E, Jefferys Joan L, Quigley Harry A, Nguyen Thao D
AI Summary
Removing sulfated GAGs stiffened human optic nerve tissue, reducing its pressure-induced strain. This suggests sGAGs influence LC biomechanics, potentially impacting glaucoma susceptibility and progression.
Abstract
Purpose
In this study, we measured the effect of the removal of sulfated glycosaminoglycans (sGAGs) on the pressure-induced strains of the human lamina cribrosa (LC).
Methods
We applied an ex vivo inflation method to measure the three-dimensional (3D) deformation response of six human LCs to pressure, before and after the degradation of chondroitin and dermatan sulfates. The experiment used a laser-scanning microscope (LSM) to acquire the second harmonic generation (SHG) signal of the collagen structure in the LC. Digital volume correlation (DVC) was used to calculate the deformation in the LC after a change in pressure from 5 to 45 mm Hg.
Results
The average strains between 5 and 45 mm Hg in the LC decreased significantly after sGAG degradation (P ≤ 0.03), with the greatest change occurring in regions of previously high strain (P ≤ 0.003) and the peripheral regions of the LC (P ≤ 0.02). The stiffening effect was greater in the LC of middle-aged (42-49 years) donors compared with those of older (64-88 years) donors (P < 0.0001).
Conclusions
The LC experienced less strain at the same pressures after most sGAGs were removed. These results suggest that the natural decrease in sGAGs within the LC with age may contribute to the stiffer inflation response of older LC to IOP. Likewise, the increase in the amount of sGAGs observed in the LC of glaucomatous eyes, may contribute to a more compliant LC, which may affect the susceptibility and progression of axon damage.
MeSH Terms
Shields Classification
Key Concepts5
The average strains between 5 and 45 mm Hg in the human lamina cribrosa (LC) decreased significantly after sulfated glycosaminoglycan (sGAG) degradation (P ≤ 0.03).
The greatest change in average strains in the human lamina cribrosa (LC) after sulfated glycosaminoglycan (sGAG) degradation occurred in regions of previously high strain (P ≤ 0.003).
The stiffening effect of sulfated glycosaminoglycan (sGAG) degradation was greater in the lamina cribrosa (LC) of middle-aged (42-49 years) donors compared with those of older (64-88 years) donors (P < 0.0001).
The natural decrease in sulfated glycosaminoglycans (sGAGs) within the lamina cribrosa (LC) with age may contribute to the stiffer inflation response of older LC to intraocular pressure (IOP).
The increase in the amount of sulfated glycosaminoglycans (sGAGs) observed in the lamina cribrosa (LC) of glaucomatous eyes may contribute to a more compliant LC, which may affect the susceptibility and progression of axon damage.
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