Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0595921 (intraocular pressure)
11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence and distribution of laminin, heparan sulfate proteoglycan and collagen types I, III and IV were immunohistologically determined in cynomolgus monkey optic nerve heads using the avidin-biotin-peroxidase complex technique. Collagen types I and III were detected within the collagenous plates of the scleral lamina cribrosa, in the septa and pia mater of the postlaminar optic nerve and in blood vessel walls in all regions of the optic nerve head. Collagen type IV, laminin and heparan sulfate proteoglycans were all localized to the margins of the collagenous laminar plates of the scleral lamina cribrosa and along the margins of the optic nerve septa and the pia mater. All three components also appeared beneath the blood vessel endothelium throughout the optic nerve head. Within the lamina cribrosa, collagen types I and III occupy the core of the scleral laminar plates and may provide structural support for optic nerve bundles exiting the eye. The distribution of collagen type IV, laminin and heparan sulfate proteoglycan corresponds to basement membranes from two sources: vascular endothelial cells and glial cells lining the axonal bundles. Abnormalities of these substances may influence optic nerve function and susceptibility to elevated intraocular pressure by altering their mechanical support functions within the nerve head, by interfering with axonal nutrition, or both.
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PMID:The extracellular matrix composition of the monkey optic nerve head. 304 74

Although glycosaminoglycans (GAGs) have been postulated to play a role in the regulation of intraocular pressure, structural localization of specific varieties of GAGs in the outflow system is necessary before their precise role can be determined. In this study, the outflow system of the cat was stained with ruthenium red to identify GAGs with the electron microscope. The composition of the ruthenium red-stainable material was determined by predigestion of tissues with testicular hyaluronidase, neuraminidase, or papain. Testicular hyaluronidase-sensitive GAGs were located on the surfaces of the endothelial cells in the trabecular meshwork and aqueous plexus, within their basal laminae, and in the amorphous tissue of the trabecular beams and tissue adjacent to the aqueous plexus. Collagen and elastic fibers throughout the outflow system were also associated with ruthenium red-stainable material that was resistant to testicular hyaluronidase. Connective tissue GAGs, but not endothelial cell-associated GAGs, were demonstrated to be complexed to protein, since they were disrupted by papain treatment. Neuraminidase-sensitive material (sialoglycoprotein) was identified only on the lumenal surface of the endothelial cells of the aqueous plexus. The complex distribution of GAGs and order polyanions in the outflow system of the cat suggests that the these macromolecules may serve more than one function.
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PMID:Distribution of glycosaminoglycans in the aqueous outflow system of the cat. 617 75

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.
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PMID:The effect of chronically elevated intraocular pressure on the rat optic nerve head extracellular matrix. 898 48

Unroofing of Schlemm's canal without entering the anterior chamber has been performed previously to lower intraocular pressure. Initial results were good, but long-term results were discouraging, and the techniques were abandoned. Recently, two variations have surfaced. Visco canalostomy is a technique devised by Robert Stegmann of South Africa. The glaucoma drainage device (Collagen Wick) was initially introduced by Koslov in Russia. These techniques are described in this article.
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PMID:Nonpenetrating filtering procedures: viscocanalostomy and collagen wick. 1079 May 84

Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure when medical treatment fails. It involves removing part of the ocular drainage apparatus. Resistance to intraocular fluid drainage is decreased, improving drainage and decreasing intraocular pressure. By avoiding anterior chamber penetration, DS diminishes frequency of the complications of filtering surgery. 24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma with elevated intraocular pressure not controlled medically. It included preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and removing most of an internal scleral flap (leaving it 1 mm smaller than the external flap), unroofing Schlemm's canal and removing fine endothelial tissue lining its inner walls. The external scleral flap was then repositioned and sutured. Collagen implants were not used. In some cases DS was combined with extracapsular cataract extraction and intraocular lens implantation. Mean intraocular pressure decreased from 24.8 +/- 3.9 mmHg initially to 12.8 +/- 4.4 mmHg 6 months after operation (p < 0.0001). There was no difference in postoperative intraocular pressure between DS as a single procedure or as part of a combined operation. Complications were mild and of short duration. If long-term follow-up shows that lowered intraocular pressures are maintained, DS should be a surgical option in earlier stages of glaucoma.
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PMID:[Non-penetrating deep sclerectomy without collagen implant for glaucoma, as single or combined surgery]. 1088 74

Purpose: Collagen solution was assessed as a possible visoelastic substance in anterior segment surgery, in terms of the depth of the anterior chamber and ocular irritation.Methods: The depth of the anterior chamber of enucleated rabbit eyes was evaluated 5 minutes after injection of collagen solution. For ocular irritation test, the aqueous humor of rabbits was replaced with collagen using sodium hyaluronate (HEALON((R))) and phosphate buffer (PB) as controls. Follow-up clinical examinations with hand-slit-lamp-microscopy, tonometry, pachymetry, and specular microscopy were performed for 7 days or 28 days, and then aqueous humor, corneal endothelium, and eye tissues were evaluated by gel electrophoresis, scanning electron microscopy, and light microscopy, respectively.Results: 2.5% to 3% collagen solution was found to be optimal for maintaining the depth of the anterior chamber. No significant differences in clinical findings such as anterior chamber and corneal thickness or in biochemical and histological findings were observed among collagen-, hyaluronate- and PB-treated groups, except for intraocular pressure which was increased in the hyaluronate-treated group, but not in the collagen-treated group.Conclusion: Collagen specifically prepared for this study seems to be an excellent auxiliary agent for anterior segment surgery, providing an appropriate anterior chamber with little ocular irritation. (Jpn Ophthalmol Soc 104:458-65, 2000)
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PMID:Study on Collagen Viscoelastic Substance as an Auxiliary Agent in Anterior Segment Surgery. Ocular Irritation Study by Replace ment of the Aqueous Humor in Rabbits. 1134 94

Purpose To use immunohistochemical techniques to identify and localize the structural macromolecules of the extracellular matrix (ECM) of the normal adult equine lamina cribrosa in order to make comparisons to the extracellular matrix of the lamina cribrosa of horses with glaucoma. METHODS: Normal eyes of five adult horses between 5 and 10 years of age were fixed in 10% neutral buffered formalin and embedded in paraffin. Polyclonal rabbit-derived antibodies against human elastin, laminin, fibrillin-1, and collagen types I, III and IV, and polyclonal goat-derived antibodies against collagen type VI were used as primary antibodies. Transverse and longitudinal histologic sections of the optic nerve head and lamina cribrosa were stained using several dilutions of the primary antibodies, biotinylated link antibody, horseradish peroxidase-labeled streptavidin, and 3,3'-diaminobenzidine as a chromogen. The immunohistochemical staining patterns were qualitatively interpreted. RESULTS: The normal adult horse lamina cribrosa labeled positively for collagen types I, III and VI, laminin, elastin and fibrillin. Collagen type VI staining of the laminar ECM was most intense, followed by labeling for collagen types III and I, respectively. Laminar blood vessels were weakly positive for laminin and slightly positive for type IV collagen. The scleral ECM of the laminar insertion zone had more intense labeling for collagen types I and VI than did the laminar plates. CONCLUSIONS: The extracellular matrix of the laminar plates of the adult equine lamina cribrosa is similar to the dog as it consists of elastic and collagen fibers (with collagen types VI, III and I). Both the normal dog and horse lamina display more intense staining of collagen type VI than is found in the ECM of the normal human lamina cribrosa. The macromolecular structure of the equine lamina cribrosa suggests that it is a very resilient structure that may provide some protection to the optic nerve axons during episodes of elevated intraocular pressure.
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PMID:Immunohistochemistry of the extracellular matrix of the normal equine lamina cribrosa. 1139 94

Drainage devices are routinely placed in the eyes of patients with glaucoma to reduce intraocular pressure (IOP) by providing controlled outflow of fluid (aqueous humor) via a filtering bleb. However, the natural wound healing response often interferes with fluid outflow by thickening the walls of the bleb over time, so that these devices rarely remain functional for more than 5 years. We investigated the use of controlled release of an antimetabolite, 5-fluorouracil (5-FU), within glaucoma drains to determine if the wound healing response could be reduced and the useful life span of the device increased. Collagen plugs containing 1.125 mg of 5-FU were placed in the silicone tubes of modified Baerveldt glaucoma drains. Eight drains with 5-FU and eight drains without 5-FU were implanted in one eye each of 16 New Zealand white rabbits: the contralateral eyes served as unoperated controls. Results were evaluated in terms of IOP, fibrous capsule thickness, macrophage density. and presence of type III collagen surrounding the drain plate, 3 and 6 months after implantation. In general, eyes implanted with antimetabolite-containing drains demonstrated significantly lower values for all evaluated parameters at 3 months and lower or equal values at 6 months, compared with the eyes not receiving 5-FU and the unoperated controls, indicating improved IOP-lowering function, reduced bleb wall thickness, and earlier achievement of a steady-state wound healing response. All eyes remained healthy throughout the 6-month duration of the study with no cytotoxicity complications in any of the eyes. Thus, biodegradable plugs placed within the silicone tubes of glaucoma drains can safely deliver 5-FU to filtering blebs over time, which could prolong the functional life of the bleb by decreasing the thickness of the anterior fibrous capsule and permitting sufficient fluid outflow to reduce IOP to physiological levels.
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PMID:Slow release of the antimetabolite 5-fluorouracil (5-FU) from modified Baerveldt glaucoma drains to prolong drain function. 1170 Aug 5

The technique of finite element analysis was applied to ocular geometry to predict the effects of mechanical loads, such as those imposed by glaucoma shunt implants, on the stress distribution and organization of the collagen fiber matrix that comprises the sclera. Axisymmetric and 2D shell models of the sclera were constructed to simulate the application of a pressure region on the exterior surface of the sclera. Both models predict redistribution of stress from the center of the pressure region to its outer edge where the magnitude of principal stresses exceeds that of any other location in the models. The models are supported by morphological changes in tissue samples from human and rabbit eyes that have been subjected to stresses similar to those depicted in the models. Analysis of scleral collagen using polarized light shows the tissue is highly organized and responsive: Collagen aligns itself along the principal stresses within the sclera. Furthermore, amount of choroidal hemorrhaging commonly associated with glaucoma shunts correlates with redistribution of mechanical stress, suggesting that pressure imposed by plate rather than reduction of intraocular pressure is responsible for hemorrhage.
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PMID:A finite element approach to predicting scleral response to mechanical stress. 1914 37

The sclera is the white outer shell and principal load-bearing tissue of the eye as it sustains the intraocular pressure. We have hypothesized that the mechanical properties of the posterior sclera play a significant role in and are altered by the development of glaucoma-an ocular disease manifested by structural damage to the optic nerve head. An anisotropic hyperelastic constitutive model is presented to simulate the mechanical behavior of the posterior sclera under acute elevations of intraocular pressure. The constitutive model is derived from fiber-reinforced composite theory, and incorporates stretch-induced stiffening of the reinforcing collagen fibers. Collagen fiber alignment was assumed to be multidirectional at local material points, confined within the plane tangent to the scleral surface, and described by the semicircular von Mises distribution. The introduction of a model parameter, namely, the fiber concentration factor, was used to control collagen fiber alignment along a preferred fiber orientation. To investigate the effects of scleral collagen fiber alignment on the overall behaviors of the posterior sclera and optic nerve head, finite element simulations of an idealized eye were performed. The four output quantities analyzed were the scleral canal expansion, the scleral canal twist, the posterior scleral canal deformation, and the posterior laminar deformation. A circumferential fiber organization in the sclera restrained scleral canal expansion but created posterior laminar deformation, whereas the opposite was observed with a meridional fiber organization. Additionally, the fiber concentration factor acted as an amplifying parameter on the considered outputs. The present model simulation suggests that the posterior sclera has a large impact on the overall behavior of the optic nerve head. It is therefore primordial to provide accurate mechanical properties for this tissue. In a companion paper (Girard, Downs, Bottlang, Burgoyne, and Suh, 2009, "Peripapillary and Posterior Scleral Mechanics--Part II: Experimental and Inverse Finite Element Characterization," ASME J. Biomech. Eng., 131, p. 051012), we present a method to measure the 3D deformations of monkey posterior sclera and extract mechanical properties based on the proposed constitutive model with an inverse finite element method.
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PMID:Peripapillary and posterior scleral mechanics--part I: development of an anisotropic hyperelastic constitutive model. 1938 81


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