Research Report Elevated pressure induced astrocyte damage in the optic nerve Chandrakumar Balaratnasingam a , William H. Morgan a , Louise Bass b , Linda Ye a , Charlotte McKnight a , Stephen J. Cringle a , Dao-Yi Yu a, ⁎ a Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia b Department of Anaesthesia, Murdoch University Veterinary Hospital, Perth, Australia ARTICLE INFO ABSTRACT Article history: Accepted 10 September 2008 Available online 24 September 2008 Astrocytes maintain an intimate relationship with central nervous system (CNS) neurons and play a crucial role in regulating their biochemical environment. A rise in neural tissue pressure in the CNS is known to lead to axonal degeneration however the response of astrocytes during the early stages of neural injury has not been studied in great detail. The optic nerve is a readily accessible model in which to study CNS axonal injury. Previous work from our laboratory has shown that an acute increase in intraocular pressure (IOP) results in axonal cytoskeleton changes and axonal transport retardation within the optic nerve head. Axonal changes occurred in a time-dependent manner with the magnitude of change being proportional to the duration of the IOP rise. Using glial fibrillary acidic protein (GFAP) as a marker of astrocytes we have now studied pressure induced changes in astrocyte structure in the optic nerve head. Using confocal microscopy we found that an increase in IOP resulted in morphological changes in the astrocytes that were consistent with previous reports of swelling. In addition there was also a decrease in GFAP intensity within these astrocytes. These changes occurred in a time-dependent manner with the chronology of change coinciding with that of axonal change. There was no evidence of apoptosis in regions where astrocyte changes were found. The present results provide evidence that in the early stages of neural tissue pressure rise there are both astrocyte and axonal injury. © 2008 Elsevier B.V. All rights reserved. Keywords: Astrocyte Intraocular pressure Glaucoma Optic nerve head Lamina cribrosa 1. Introduction Astrocytes are the most abundant cell type within the central nervous system (CNS) and play a crucial role in maintaining neuronal well being (De Keyser et al., 2008). Although their primary role in a physiological environment is to support neuronal function, significant aberrations in cellular home- ostasis can result in activation of astrocytes causing them to become the primary mediators of neuronal damage (Neufeld and Liu, 2003). Glial fibrillary acidic protein (GFAP) is a type III intermediate filament which is a major constituent of astro- cytes and a marker commonly used to study the distribution and morphology of these cells (Eng et al., 2000). Within the CNS, astrocytes typically increase GFAP expression in an activated state and decrease GFAP expression in conditions of ischemia and injury (Norenberg, 1994). A rise in cerebrospinal fluid (CSF) pressure within the brain occurs in congenital hydrocephalus but also in many acquired conditions such as cerebral contusion, haemorrhage and infection (Rangel-Castillo and Robertson, 2006). A rise in CSF pressure causes a proportional increase in neuronal tissue pressure which over time has been shown to result in both BRAIN RESEARCH 1244 (2008) 142 – 154 ⁎ Corresponding author. Centre for Ophthalmology and Visual Science, The University of Western Australia, Nedlands, Western Australia 6009, Australia. Fax: +618 9381 0700. E-mail address: dyyu@cyllene.uwa.edu.au (D.-Y. Yu). 0006-8993/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2008.09.044 available at www.sciencedirect.com www.elsevier.com/locate/brainres