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

Authors

  • Chao Dai,

    1. Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London WC1N 3BG, United Kingdom
    2. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China
    Search for more papers by this author
  • Peng T. Khaw,

    1. NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London EC1V 9EL, United Kingdom
    Search for more papers by this author
  • Zheng Qin Yin,

    1. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China
    Search for more papers by this author
  • Daqing Li,

    1. Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London WC1N 3BG, United Kingdom
    Search for more papers by this author
  • Geoffrey Raisman,

    Corresponding author
    1. Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London WC1N 3BG, United Kingdom
    • Spinal Repair Unit, Institute of Neurology, UCL Queen Square, London WC1N 3BG, United Kingdom
    Search for more papers by this author
  • Ying Li

    1. Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London WC1N 3BG, United Kingdom
    Search for more papers by this author

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). © 2011 Wiley Periodicals, Inc.

Ancillary