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Sarah Quillen, Julie Schaub, Mary Ellen Pease, Elizabeth Cone Cone-Kimball, Arina Korneva, Harry A Quigley; Changes in Astrocyte Morphology in the Mouse Optic Nerve Head with Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2003.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the responses of optic nerve head (ONH) astrocytes due to sustained intraocular pressure (IOP) elevation in mice.
IOP was elevated for 1 day to 6 weeks by microbead injection in 206 eyes of 4 strains of mice. Astrocyte changes were studied by transmission electron microscopy (TEM) including immunogold molecular localization & by laser scanning microscopy (LSM) with fluorescent antibodies to integrin β1, actin & glial fibrillary acidic protein (GFAP).
Astrocytes in a normal ONH expressed integrin β1 by LSM & immunogold labeling. By TEM, electron dense junctional complexes were found only on cell membrane zones bordering their basement membranes (BM) at the peripapillary sclera (PPS) & ONH capillaries. At 1-3 days after IOP elevation, abnormal extracellular spaces appeared between astrocytes near PPS and axonal vesical & mitochondrial accumulation indicated axonal transport blockade. A dramatic increase in smooth muscle actin was seen 3 days after IOP increase. By 1 week, abnormal spaces increased, new collagen formation began to occur & astrocytes separated from their BM, leaving behind cell membrane fragments. Junctional complexes separated or were absent. Astrocyte processes reoriented from horizontally across the ONH to parallel to axons. Astrocyte proliferation was modest during first week by Ki67 labeling, while only occasional apoptotic astrocytes were observed by TEM & TUNEL. At 6 weeks, abnormal spaces are filled with collagen.
Astrocytes normally exhibit transcellular junctions with their BM which are disrupted by extended IOP elevation. Responses to IOP elevation include reorientation of cell processes, new collagen formation & mild cell proliferation.
This is a 2020 ARVO Annual Meeting abstract.
Figure 1: A: Intracellular electron dense junctions were found only next to the BM of the astrocytes at the PPS boundary (arrowhead). B: After 1wk IOP elevation, loss of junctional complexes with areas of small membranous blebs at former attachment sites (arrowhead). Note axonal transport blockage. C: Abnormal, new collagen formation among astrocytes in chronic glaucoma ONH. Scale bar=200um
Figure 2: A: Immunogold label of integrin β1 (circles) near PPS/ astrocyte boundary. B: Junctional complexes separate from inner cell membrane with 1 week IOP elevation. Scale bar=500um
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