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Astrocyte responses to experimental glaucoma in mouse optic nerve head
Sarah Quillen1, Julie Schaub1, Harry Quigley1
1Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, United States of America.
Plos One
|August 22, 2020
Summary
Sustained high intraocular pressure (IOP) disrupts optic nerve head astrocyte junctions with their basement membranes. This leads to astrocyte reorientation, new collagen formation, and cell proliferation in mice.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Astrocytes play crucial roles in maintaining optic nerve head (ONH) structure and function.
- Optic nerve head (ONH) astrocytes interact with the basement membrane (BM) via specialized junctional complexes.
- Alterations in astrocyte-BM interactions are implicated in optic neuropathies.
Purpose of the Study:
- To investigate the cellular and molecular responses of optic nerve head (ONH) astrocytes to sustained elevated intraocular pressure (IOP) in a mouse model.
- To characterize the structural changes and molecular alterations in astrocytes under conditions of chronic IOP elevation.
Main Methods:
- Intracameral microbead injection was used to induce sustained elevated intraocular pressure (IOP) in mice for durations ranging from 1 day to 6 weeks.
- Transmission electron microscopy (TEM) with immunogold labeling was employed to visualize astrocyte ultrastructure and molecular localization.
- Laser scanning microscopy (LSM) with immunofluorescence was used to assess the expression of integrin β1, α-dystroglycan, and glial fibrillary acidic protein (GFAP).
- Astrocyte proliferation and apoptosis were quantified using Ki67 and TUNEL labeling, respectively.
Main Results:
- In normal ONH, astrocytes exhibited integrin β1 and α-dystroglycan at electron-dense junctional complexes with their basement membranes (BM) at the peripapillary sclera (PPS) and capillaries.
- Following IOP elevation, abnormal extracellular spaces emerged between astrocytes near the PPS, accompanied by axonal transport deficits (vesicular and mitochondrial accumulation).
- By 1 week of elevated IOP, these spaces enlarged, new collagen was formed, and astrocytes detached from their BM, with junctional complexes becoming disrupted or absent.
- Astrocyte proliferation was modest in the first week, with minimal apoptosis observed.
Conclusions:
- Normal astrocyte-BM junctions are disrupted by prolonged elevation of intraocular pressure (IOP).
- Optic nerve head (ONH) astrocyte responses to sustained IOP elevation include reorientation of cellular processes, synthesis of new collagen, and increased cell proliferation.
- These findings highlight the vulnerability of astrocyte-BM interactions in the ONH to mechanical stress and suggest potential mechanisms contributing to optic nerve damage.
