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Arina Korneva, Elizabeth Cone Cone-Kimball, Thao D Nguyen, Harry A Quigley; Regional Mechanical Strains in Mouse Astrocytic Lamina and Peripapillary Sclera after Chronic IOP Elevation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):996.
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© ARVO (1962-2015); The Authors (2016-present)
To measure astrocytic mechanical responses in glaucoma, we characterized the local distribution of strains in the astrocytic lamina (AL) and peripapillary sclera (PPS) of mouse explanted globes.
Transgenic mice expressing green fluorescent protein in all astrocytes under the glial fibrillary acidic protein promoter (FVB/N-Tg(GFAP-GFP)14Mes) were studied after 3 days and 6 weeks of bead-induced intraocular pressure (IOP) elevation in one eye, and compared to both naive and contralateral control eyes. Inflation tests of enucleated intact mouse eyes were performed by increasing IOP from 10 to 30 mmHg, and mechanical strains were calculated by digital volume correlation of laser scanning microscopy images (Nguyen et al., 2018) of the fluorescence signal in AL and the second harmonic generated signal in PPS. Regional in-plane strain distributions were characterized using built-in MATLAB functions (Mathworks, Inc), statistical analysis performed with GraphPad.
In-plane nasal-temporal strain (Exx) was twice the superior-inferior (Eyy) strain, and neither was uniform across the AL. Exx increased from the periphery to the center, with a slope of 0.43%/μm, with astrocytic processes under 4.2% tension (median Exx) centrally, but under -0.8% compression peripherally. Similar pattern was quantified for Eyy. After 3 days of elevated IOP, Exx decreased by 35% and was more uniform, slope of 0.19%/μm (p=0.03) , with astrocytic processes under tension across the AL. After 6 weeks of elevated IOP, strain returned to control magnitude and distribution. In PPS, mean in-plane strains were 10x smaller, 0.1±0.2%.
Normal mechanical strains are substantially higher in the AL than PPS, with greater AL nasal-temporal strain. In-plane in the AL, strain decreased from peak tensile centrally to smaller compressive strain peripherally. After chronic elevated IOP, strain initially changed, but returned to control magnitude and distribution 6 weeks later. Strain evolution in mouse glaucoma will be compared to companion studies of ultrastructural changes in AL astrocytes.
This is a 2020 ARVO Annual Meeting abstract.
Exx strain map in AL averaged along nerve axis.
Exx strain in AL, averaged along Y position and nerve axis (Z). After initial IOP elevation, central (A) to peripheral difference (B) is less dramatic (B, C) but returns to normal after 6 weeks (B, D). Mean±SD
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