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Dan Midgett, Harry A Quigley, Thao D Nguyen; Removing Glycosaminoglycans Produced a Stiffer Human Optic Nerve Head. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3163.
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© ARVO (1962-2015); The Authors (2016-present)
The amount of sulfated glycosaminoglycans (sGAGs) in the lamina cribrosa has been shown to increase with primary open-angle glaucoma in monkeys (Fukuchi et al. 1994) and in humans with normal pressure glaucoma (Tezel et al. 1999). The amount of sGAGs also decreases in humans with age (Albon et al. 2000). This experiment studied for the first time the change in the pressure-induced strains in the ONH caused by the removal of sGAGs.
Five human eyes from 4 donors (ages 42, 49, 63, 88) were tested within 48 hours post-mortem. The optic nerve was cut flush with the sclera to expose the LC, and the cornea, anterior sclera, choroid, and retina were removed. The posterior sclera was incubated at 37°C for 4 hours in a Trizma buffer and mounted on an inflation chamber. The pressure was raised to 5, 10, and 45 mmHg and the specimen was equilibrated for 30 minutes at each pressure before imaging. A Zeiss LSM 710, tuned to 780nm, was used to acquire Z-stacks of the LC at each pressure using second harmonic generation (SHG). The specimen was removed from the inflation chamber, incubated at 37°C for 4 hours in a Trizma solution containing chondroitinase ABC (ChABC), remounted, and subjected to the same pressurization and imaging protocol. A digital volume correlation algorithm (Midgett et al. 2016) was used to analyze the SHG volumes to calculate the 3D displacement fields between pressures. ONH strains were calculated from high order polynomial functions fit to the 3D displacement fields. Strains in the nasal-temporal (NT) and inferior-superior (IS) directions and maximum principal strain were averaged and compared before and after sGAG degradation using a paired t-test (n=5).
Displacements and strains in the ONH were smaller after 4 hours of sGAG degradation using ChABC. The strain at 45 mmHg decreased significantly along the IS direction (3.08±1.69% to 2.26±1.30%, p=0.0335). A smaller decrease was measured along the NT direction (2.35±0.99% to 1.88±0.78%, p=0.097). The maximum principal strain was reduced from 4.54±1.98% to 3.92±1.74% (p=0.0212).
The removal of sGAGs resulted in a stiffer LC response to pressure. Changes in the amount of sGAGs associated with glaucoma and age may induce significant alterations to the IOP-induced strains of the LC, which may affect the susceptibility and progression of glaucomatous axon damage.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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