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Structural basis of glaucoma: the fortified astrocytes of the optic nerve head are the target of raised intraocular pressure

Dai, C; Khaw, PT; Yin, ZQ; Li, D; Raisman, G; Li, Y; (2012) Structural basis of glaucoma: the fortified astrocytes of the optic nerve head are the target of raised intraocular pressure. Glia , 60 (1) pp. 13-28. 10.1002/glia.21242. Green open access

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STRUCTURAL BASIS OF GLAUCOMA REVISED.pdf

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Abstract

Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as they pass through the optic nerve head (ONH). The massive connective tissue structure of the human lamina cribrosa is generally assumed to be the pressure transducer responsible for the damage. The rat, however, with no lamina cribrosa, suffers the same glaucomatous response to raised IOP. Here, we show that the astrocytes of the rat ONH are "fortified" by extraordinarily dense cytoskeletal filaments that would make them ideal transducers of distorting mechanical forces. The ONH astrocytes are arranged as a fan-like radial array, firmly attached ventrally to the sheath of the ONH by thick basal processes, but dividing dorsally into progressively more slender processes with only delicate attachments to the sheath. At 1 week after raising the IOP by an injection of magnetic microspheres into the anterior eye chamber, the fine dorsal processes of the ONH astrocytes are torn away from the surrounding sheath. There is no indication of distortion or compression of the axons. Subsequently, despite return of the IOP toward normal levels, the damage to the ONH progresses ventrally through the astrocytic cell bodies, resulting in complete loss of the fortified astrocytes and of the majority of the axons by around 4 weeks. We propose that the dorsal attachments of the astrocytes are the site of initial damage in glaucoma, and that the damage to the axons is not mechanical, but is a consequence oflocalized loss of metabolic support from the astrocytes (Tsacopoulos and Magistretti (1996) J Neurosci 16:877-885).

Type: Article
Title: Structural basis of glaucoma: the fortified astrocytes of the optic nerve head are the target of raised intraocular pressure
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/glia.21242
Publisher version: http://dx.doi.org/10.1002/glia.21242
Language: English
Additional information: This is the peer reviewed version of the following article: Dai, C; Khaw, PT; Yin, ZQ; Li, D; Raisman, G; Li, Y; (2012) Structural basis of glaucoma: the fortified astrocytes of the optic nerve head are the target of raised intraocular pressure. Glia, 60 (1) pp. 13-28, which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms).
Keywords: Animals, Astrocytes, Axons, Disease Models, Animal, Female, Glaucoma, Intraocular Pressure, Microscopy, Electron, Transmission, Optic Disk, Optic Nerve Diseases, Rats, Retinal Ganglion Cells, Stress, Physiological, Time Factors
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/1326576
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