The Contribution of Sulfated Glycosaminoglycans to the Inflation Response of the Human Optic Nerve Head

• Published in: Investigative ophthalmology & visual science 2018-06, Vol.59 (7), p.3144-3154
• Main Authors: Midgett, Dan E, Jefferys, Joan L, Quigley, Harry A, Nguyen, Thao D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomechanical Phenomena; Chondroitin Sulfates - metabolism; Collagen - metabolism; Dermatan Sulfate - metabolism; Female; Glaucoma; Glycosaminoglycans - physiology; Humans; Imaging, Three-Dimensional; Intraocular Pressure - physiology; Male; Middle Aged; Optic Disk - physiopathology; Pressure; Sclera - metabolism; Stress, Mechanical
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.18-23845

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). 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. 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). 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.