The effect of chronically elevated intraocular pressure on the rat optic nerve head extracellular matrix

Elaine C. Johnson, John C. Morrison, Susan Farrell, Lisa Deppmeier, C. G. Moore, M. R. Mcginty

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Abstract

The extracellular matrix of the optic nerve head is altered in both human glaucoma and in experimental primate models of this disease. However, the relationship of this change to glaucomatous optic nerve degeneration is unknown. This report describes similar matrix alterations in rats with unilateral elevated intraocular pressure. Brown Norway rats received episcleral vein injections of hypertonic saline to produce prolonged elevations of intraocular pressure. After up to 6 months of pressure elevation, optic nerve head sections from the rats were evaluated by light microscopic immunohistochemistry using antibodies to collagens I, III, IV and VI, laminin, elastin and chondroitin and dermatan sulfate proteoglycans. In experimental eyes with 11 days or more of pressure elevation, depositions of collagen IV, collagen VI and laminin were found within regions of the optic nerve head that, in normal eyes, are occupied solely by nerve bundles. Collagen I and III deposition appeared to be more dependent on the level and duration of the pressure rise. Eyes with lower mean intraocular pressures showed deposits of interstitial collagens primarily at the level of the sclera, while eyes with higher mean pressure elevations had depositions in the neck regions as well. Chondroitin and dermatan sulfate proteoglycans were deposited in a pattern similar to that of collagen I. No extracellular matrix deposition was seen in the orbital optic nerve in any experimental eye. These extracellular matrix changes in rats replicate previous findings in human glaucomatous eyes and monkey eyes with experimentally elevated pressures. They also suggest a sequence of extracellular matrix protein deposition in response to pressure elevation. The optic nerve head deposition of matrix materials in response to elevated intraocular pressures may affect the susceptibility of remaining axons to pressure by changing the physical properties of their support tissues, by affecting the support functions of astrocytes and by changing the microenvironment of injured axons. This model may be useful for studying these and other aspects of the process of axonal injury resulting from elevated intraocular pressure.

Original languageEnglish (US)
Pages (from-to)663-674
Number of pages12
JournalExperimental Eye Research
Volume62
Issue number6
DOIs
StatePublished - Jun 1996

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Keywords

  • collagen
  • extracellular matrix
  • glaucoma
  • intraocular pressure
  • lamina cribrosa
  • optic nerve head
  • proteoglycan
  • rat model, astrocyte

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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