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 hu man glaucoma and in experimental primate models of this disease, Howev er, the relationship of this change to glaucomatous optic nerve degene ration 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 p rolonged elevations of intraocular pressure. After up to 6 months of p ressure elevation, optic nerve head sections from the rats were evalua ted by light microscopic immunohistochemistry using antibodies to coll agens I, III, IV and VI, laminin, elastin and chondroitin and dermatan sulfate proteoglycans. In experimental eyes with 11 days or more of p ressure elevation, depositions of collagen IV, collagen VI and laminin were found within regions of the optic nerve head that, in normal eye s, are occupied solely by nerve bundles. Collagen I and III deposition appeared to be more dependent on the level and duration of the pressu re rise. Eyes with lower mean intraocular pressures showed deposits of interstitial collagens primarily at the level of the sclera, while ey es with higher mean pressure elevations had depositions in the neck re gions as well. Chondroitin and dermatan sulfate proteoglycans were dep osited in a pattern similar to that of collagen I. No extracellular ma trix deposition was seen in the orbital optic nerve in any experimenta l eye. These extracellular matrix changes in rats replicate previous f indings in human glaucomatous eyes and monkey eyes with experimentally elevated pressures. They also suggest a sequence of extracellular mat rix protein deposition in response to pressure elevation. The optic ne rve head deposition of matrix materials in response to elevated intrao cular pressures may affect the susceptibility of remaining axons to pr essure by changing the physical properties of their support tissues, b y affecting the support functions of astrocytes and by changing the mi croenvironment of injured axons, This model may be useful for studying these and other aspects of the process of axonal injury resulting fro m elevated intraocular pressure. (C) 1996 Academic Press Limited