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 etiology, pathogenesis and mechanism of optic nerve damage in primary open angle glaucoma (POAG) and low tension glaucoma (LTG) were investigated by experimental glaucoma in monkey and by follow-up studies of many patients over 15 years, by pathohistological and immunohistochemical analysis. 1) LTG was proved to be a real glaucoma, showing pressure-dependent optic nerve damage. The pathological entity was a primary weakness of the lamina cribrosa (LC), and therefore even normal pressure could deform the LC. Due to backward distortion of LC the channels were disarranged and twisted, inducing mechanical optic nerve damage. There was no active vascular damage or vascular constriction at the site of the optic nerve damage. The filling defects of the advanced glaucomatous optic disc were not the cause of optic nerve damage, but the result of regressive vascular change after axon bundle loss. Splinter hemorrhage of the optic disc might be the result of the same process. 2) The weakness of LC might be induced by the abnormal metabolism of the extracellular matrix of the LC. 3) To arrest the progressive optic nerve damage in LTG, the intraocular pressure (IOP) should be maintained under 12, or ideally, 10 mmHg. 4) The optic nerve damage in POAG was not only pressure-dependent, but also dependent on the weakness of the LC, as in the case of LTG. In the early stage the IOP should be under 19 mmHg, in the advanced stage under 14 mmHg in order to arrest progression for over 15 years. 5) In advanced experimental glaucoma of monkeys, the LC showed reduction of elastin, fragmentation of collagen, and change of proteoglycans. 6) As in the LC, the trabecular meshwork also showed abnormal metabolism and abnormal deposits on the extracellular matrix in POAG, and LTG as well. 7) POAG and LTG might belong to the same family in which common abnormal metabolism of LC and trabecular meshwork induce various clinical features.
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PMID:[Primary open angle glaucoma and low tension glaucoma--pathogenesis and mechanism of optic nerve damage]. 148 70

Using light microscopic immunohistochemistry, we studied the immunolocalization and immunoreactivity of the extracellular matrix, including collagen types III, IV, VI, laminin, and alpha elastin in the lamina cribrosa of monkey eyes with normal and experimentally chronic glaucoma. Our results showed: (1) abnormal linearlike immunodeposits of both collagen type IV and laminin in the margin of the lamina cribrosa with significant density in the glaucomatous eyes; (2) the immunoreactivity of collagen type III resembled that of the normal eye, but was slightly stronger at the laminar surface; (3) findings with collagen type VI resembled those of type III with an enhanced linearlike staining surrounding the nerve-fiber bundles. Furthermore, staining of alpha elastin demonstrated dramatic changes in both reactivity and localization. The lamina cribrosa of glaucomatous eyes showed a markedly reduced immunoreactivity as well as an irregular, interrupted pattern. These observations suggest that the changes might be a secondary to the long-standing elevation of intraocular pressure. The alteration of these macromolecules may modify the course of glaucomatous optic damage.
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PMID:Extracellular matrix changes of the optic nerve lamina cribrosa in monkey eyes with experimentally chronic glaucoma. 152 6

Unilateral glaucomatous optic neuropathy and optic nerve transections were produced in cynomolgus monkeys, and the optic nerve heads were examined by light and electron microscopic immunohistochemistry. Glaucomatous nerve heads showed increased labeling for collagen type IV along the margins of beams in the lamina cribrosa, due to accumulation of basement membrane-like materials. We also noted material in the pores of the laminar beams that labeled with antibodies to collagen types I, III and IV, but not elastin. In transected eyes, increased type IV labeling of laminar beam margins resulted solely from redundant astrocyte basement membranes. Extracellular matrix deposition within laminar pores was not observed following optic nerve transection; hence this may be a selective response to elevated intraocular pressure. This response may alter the biochemical composition of the lamina cribrosa and its function in patients with elevated intraocular pressure.
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PMID:Optic nerve head extracellular matrix in primary optic atrophy and experimental glaucoma. 236 39

Spontaneous glaucoma in the beagle was exhibited after 6 months of age by elevated intraocular pressures and open iridocorneal angles followed by secondary changes. In order to appreciate alterations of the aqueous outflow apparatus in dogs with this autosomal recessive disorder, the eyes of beagles with inherited glaucoma at ages 1 day through 34 months were examined by light, scanning and transmission electron microscopy. Developmentally, no notable differences were observed between normal and preglaucomatous outflow channels through 7 months of age. In 12-month-old glaucomatous chamber angles clustered basement membrane-like material was found scattered throughout the outer corneoscleral trabecular meshwork. In this region elastin-like fibers appeared to be more numerous and arranged less regularly than age-matched normal eyes. Occasional trabecular cells within the corneoscleral trabecular meshwork possessed small clusters of serrated, opaque rods within their cytoplasm. In the older glaucomatous dogs these changes were more generalized and extensive throughout the entire corneoscleral trabecular meshwork. In some individual eyes the anterior chamber angles were observed to be narrow both clinically and histologically. These outflow apparatuses were additionally characterized by compressed, less organized trabeculae with a concomitant build-up of extracellular materials. No correlation was found between the shallowness of the iridocorneal angle and increase in intraocular pressure. Primary glaucoma in the beagle during its earlier phases compared more positively to open-angle glaucoma in man than any of the other spontaneous types in animals.
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PMID:Ultrastructural changes in the aqueous outflow apparatus of beagles with inherited glaucoma. 292 24

We used immunoperoxidase staining and double immunofluorescent staining to demonstrate the macromolecular components of the extracellular matrix of the lamina cribrosa from young human donors. The cribriform plates were made up of a core of elastin fibers with a sparse, patchy distribution of collagen type III. The plates were coated with collagen type IV and laminin; these basement membrane components were presumably made by the astrocytes that were distributed on the surfaces of the plates. The insertion of the lamina cribrosa in the sclera was made up of concentric, circumferential elastin fibers that surrounded the lamina cribrosa and were continuous with the elastin in the cribriform plates. Astrocytic processes extended into the bundles of elastin fibers, whereas the basement membrane components extended into the sclera. The mechanical properties of the macromolecules of the extracellular matrix of the lamina cribrosa may make this tissue compliant and sensitive to intraocular pressure. Perhaps individual differences in the macromolecular components of this tissue contribute to the glaucomatous changes in the optic nerve head.
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PMID:Extracellular matrix of the human lamina cribrosa. 331 74

We evaluated histochemically the distribution of proteoglycans in the trabecular tissue of goniodysgenetic (developmental) glaucoma. Nine trabecular tissue specimens obtained at trabeculectomy from seven patients with goniodysgenetic glaucoma were stained with either cuprolinic blue or cupromeronic blue in combination with a series of enzyme and nitrous acid treatments. Within the extracellular matrix of the trabecular meshwork, many cupromeronic blue- or cuprolinic blue-positive filaments were observed in association with collagen fibrils, basal lamina, and basal lamina-like material. The extracellular matrices of elastin-like fibers, fine fibrillar materials, and fine granular materials were free from any reaction products. The enzyme and nitrous acid treatments disclosed that the reaction products associated with collagen fibrils represented both chondroitin sulfate and dermatan sulfate types, while those with basal lamina and basal lamina-like material represented heparan sulfate-type proteoglycans. Extensive accumulations of basal lamina-like material contained a great deal of heparan sulfate-type proteoglycans in the thick subcanalicular tissue of goniodysgenetic glaucoma. These results indicate that the class and distribution of proteoglycans in the goniodsygenetic trabecular tissues are virtually the same as that in the normal tissues. However, the large accumulation of basal lamina-like material with heparan sulfate-type proteoglycans can be one of the causes of the intraocular pressure increase in goniodysgenetic glaucoma.
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PMID:Distribution and characterization of sulfated proteoglycans in the trabecular tissue of goniodysgenetic glaucoma. 819 58

Evidence that elastic fibers with elastin exists in the trabecular meshwork (TM) and play an important role in aqueous outflow resistance is presented. The elastic fibers consist of abundant microfibrillar components containing glycoproteins and amorphous components containing elastin. If TM tissues are digested with elastase, the cells composing trabecular sheets and Schlemm's canal are separated with a decrease of elastin and come in contact with each other with reproduction of elastin. When the anterior segments of eyes are perfused with elastase, the intraocular pressure drops with a decrease of outflow resistance. A large quantity of elastin exists in fine fibrils lying underneath the trabecular wall of Schlemm's canal in primary open angle glaucoma (POAG) eyes, in pseudoexfoliation (PE) materials of PE glaucoma eyes and in basement membrane and fine fibril-like materials of steroid glaucoma eyes. In congenital and juvenile glaucoma eyes, however, instead of elastin, fibronectin localizes in basement membrane and fine fibril-like materials. When TM tissues respond to steroid hormone, the tissues synthesize and secret microfibrils and elastin, components of the elastic fibers. Elastin gene expresses in human TM. Orally administered elastase is transferred in aqueous humor and digests elastin in TM. Therefore it is possible that such a drug decreases the outflow resistance of glaucoma eyes.
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PMID:[Trabecular meshwork and elastin]. 857 52

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

The functional significance of Hyaluronan (HA) present in the cribriform layer of Schlemm's canal is not known. It may contribute to the actual outflow resistance but the relatively inert molecule might also be necessary to prevent adherence of larger molecules to the cribriform network. Thus HA might rather prevent an increase in outflow resistance. It is well known that treatment with Dexamethasone (DM) in a number of patients leads to an increase in intraocular pressure presumably due to an increase in outflow resistance. To clarify whether an imbalance in HA formation might be involved in these changes we have treated confluent cultures of human trabecular cells as well as control cell lines (ciliary muscle cells, scleral fibroblasts) with 500 nM DM for 24 hr or 12 days and have measured HA-synthesis using incorporation assays with 0.05 m D-[6-3H] Glucosamine hydrochloride. In all six cell lines investigated there was a significant decrease in HA-synthesis following short and long term treatment with DM when compared with the untreated controls. This reaction of trabecular cells to DM treatment is different from the DM effect reported on the synthesis of many other components of the extracellular matrix like fibronectin and elastin which increase after DM treatment. If the DM-effect seen in cell cultures plays a role in vivo decreased formation in HA could result in impaired function of the outflow pathways.
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PMID:Dexamethasone treatment decreases hyaluronan-formation by primate trabecular meshwork cells in vitro. 922 71

Elastin is a major component of the extracellular matrix (ECM) of the lamina cribrosa in the optic nerve head in humans and nonhuman primates. The lamina cribrosa appears to be the site of damage to the retinal ganglion cell axons in glaucomatous optic neuropathy, characterized in many patients by elevated intraocular pressure (IOP). Type 1B astrocytes are the major cell type in the lamina, synthesize elastic fibers during development, express increased elastin mRNA, and synthesize abnormal elastin in glaucoma. In this study, we determined the effect of elevated hydrostatic pressure on the synthesis of elastin by type 1B astrocytes in culture. Type 1B astrocytes were exposed to gradients of hydrostatic pressure and tested for proliferation, morphology, synthesis, and deposition of elastin. Trichloroacetic acid (TCA) and immunoprecipitation of radiolabeled protein determined total new protein and elastin synthesis. Proteins from the conditioned media were analyzed by Western blot. Levels of elastin mRNA were determined by in situ hybridization. Cell proliferation increased approximately 2-fold after exposure to pressure for one day, approximately 5-fold after 3 and 5 days of exposure to pressure. Confocal and electron microscopic cytochemistry showed a marked increase in intracellular elastin in astrocytes exposed to pressure, as compared with controls. Intracellular elastin was associated with the RER-Golgi region and with the cytoskeleton. Total protein and elastin synthesis increased significantly (P < 0.05) at 3- and 5-day exposure to pressure, as well as the level of elastin mRNA. Elastin protein in the media increased with the level of pressure. These results indicate that hydrostatic pressure stimulates type 1B astrocytes to synthesize and secrete soluble elastin into the media. In glaucoma, type 1B astrocytes may respond to IOP-related stress with increased expression of elastin and formation of elastotic fibers leading to loss of elasticity and tissue remodeling.
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PMID:Hydrostatic pressure stimulates synthesis of elastin in cultured optic nerve head astrocytes. 1100 12


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