The Effect of Chronically Elevated Intraocular Pressure on the Rat Optic Nerve Head Extracellular Matrix

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 unilatera...

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Published in:Experimental eye research Vol. 62; no. 6; pp. 663 - 674
Main Authors: JOHNSON, ELAINE C., MORRISON, JOHN C., FARRELL, SUSAN, DEPPMEIER, LISA, MOORE, C.G., MCGINTY, M.R.
Format: Journal Article
Language:English
Published: London Elsevier Ltd 01-06-1996
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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.
AbstractList 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.
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.
Author MOORE, C.G.
JOHNSON, ELAINE C.
MCGINTY, M.R.
DEPPMEIER, LISA
FARRELL, SUSAN
MORRISON, JOHN C.
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Issue 6
Keywords rat model
intraocular pressure
glaucoma
lamina cribrosa
collagen
astrocyte
optic nerve head
extracellular matrix
proteoglycan
Eye disease
Vertebrata
Mammalia
Optic nerve
Visual pathway
Rat
Glaucoma (eye)
Animal
Rodentia
Extracellular matrix
Intraocular pressure
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Snippet The extracellular matrix of the optic nerve head is altered in both human glaucoma and in experimental primate models of this disease. However, the...
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SubjectTerms Animals
astrocyte
Biological and medical sciences
collagen
Collagen - analysis
Elastin - analysis
extracellular matrix
Extracellular Matrix - chemistry
glaucoma
Glaucoma and intraocular pressure
Immunohistochemistry
intraocular pressure
Intraocular Pressure - physiology
lamina cribrosa
Laminin - analysis
Male
Medical sciences
Ocular Physiological Phenomena
Ophthalmology
Optic Disk - ultrastructure
optic nerve head
proteoglycan
Proteoglycans - analysis
rat model
Rats
Rats, Inbred BN
Title The Effect of Chronically Elevated Intraocular Pressure on the Rat Optic Nerve Head Extracellular Matrix
URI https://dx.doi.org/10.1006/exer.1996.0077
https://www.ncbi.nlm.nih.gov/pubmed/8983948
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