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Arina Korneva, Cathy Nguyen, Julie Schaub, Thao D Nguyen, Harry A Quigley; Biomechanical effects on the mouse optic nerve head in experimental scleral crosslinking in glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6188.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma damage at the optic nerve head (ONH) is related to intraocular pressure (IOP)-generated stress. Since experimental glaucoma-induced axonal damage was exacerbated by scleral cross-linking (Kimball et al., 2014), we studied the effects of this pretreatment on the mechanical response and glaucomatous damage in the ONH region. We hypothesize that greater scleral cross-linking would deleteriously redistribute the deformation of the cellular lamina cribrosa and optic nerve in mouse glaucoma model.
CD1 albino and mice expressing green fluorescent protein (GFP) under the GLT1 promoter were studied after 3 days of bead-induced glaucoma. A subset had subconjunctival injections of 0.5M glyceraldehyde for 1 week. Quantitative immunohistochemistry was performed for amyloid precursor protein (APP) and myelin basic protein (MBP) to measure change in length of optic nerve and degree of transport blockade in the ONH. GFP-GLT1 mice underwent biomechanical inflation testing in a published explant model by laser scanning microscopy and digital volume correlation-based strain calculations (Nguyen et al., 2018).
1) Crosslinking did not alter the unmyelinated optic nerve length, as measured from Bruch’s membrane opening to the labeled myelin line (228.7±32.7µm, control vs. 215.6±35.2µm, treated). However, crosslinking exacerbated the glaucoma-induced (288.8±40.9µm) lengthening of the optic nerve to 337.4±45.5µm. 2) Accumulation of APP in the ONH and unmyelinated nerve were greater after crosslinking with 3 days of IOP elevation compared to controls. 3) Overall scleral expansion during inflation testing was decreased after in vivo crosslinking in a previous study (Kimball et al., 2014). In analysis of the local mechanical response of the ONH (astrocytic lamina), nasal-temporal strain was 0.037±0.027 compared to 0.029±0.016 in control. ONH strains were minimal in the inferior-superior directions. ONH circumference increase on acute inflation was greater in treated eyes (median: 3.8% vs 3.1%). Strains in peripapillary sclera will be presented.
Glyceraldehyde crosslinking of sclera in mice exacerbates glaucomatous changes in the cellular components of the optic nerve and axonal transport obstruction. Together with elevated IOP-induced mechanical stress on the ONH, these effects probably contribute to the greater neuronal loss in a chronic glaucoma model after cross-linking.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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