elastin and Glaucoma

The pre-Descemet's layer/Dua's layer, also termed the Dua-Fine layer and the pre-posterior limiting lamina layer, lies anterior to the Descemet's membrane in the cornea, is 10 μm (range 6-16) thick, made predominantly of type I and some type VI collagen with abundant elastin, more than any other layer of the cornea. It has high tensile strength (bursting pressure up to 700 mm of Hg), is impervious to air and almost acellular. At the periphery it demonstrates fenestrations and ramifies to become the core of the trabecular meshwork, with implications for intraocular pressure and glaucoma. It has been demonstrated in some species of animals. The layer has assumed considerable importance in anterior and posterior lamellar corneal transplant surgery by improving our understanding of the behaviour of corneal tissue during these procedures, improved techniques and made the surgery safer with better outcomes. It has led to the innovation of new surgical procedures namely, pre-Descemet's endothelial keratoplasty, suture management of acute hydrops, DALK-triple and Fogla's mini DALK. The discovery and knowledge of the layer has introduced paradigm shifts in our age old concepts of Descemet's membrane detachment, acute corneal hydrops in keratoconus and Descemetoceles, with impact on management approaches. It has been shown to contribute to the pathology and clinical signs observed in corneal infections and some corneal dystrophies. Early evidence suggests that it may have a role in the pathogenesis of keratoconus in relation to its elastin content. Its contribution to corneal biomechanics and glaucoma are subjects of current investigations.

Topics: Corneal Transplantation; Descemet Membrane; Edema; Elastin; Glaucoma; Humans; Keratoconus

Sleep apnea syndrome (SAS) is a disease characterized by recurrent complete or partial upper airway obstructions during sleep. The majority of patients with SAS demonstrate this obstruction either at the nasopharynx or the oropharynx. Risk factors for SAS include obesity, male gender, upper airway abnormalities, alcohol use, snoring, and neck girth of more than 17 in. in men or 16 in. in women. Reported ophthalmic findings in patients with SAS include floppy eyelid syndrome (FES), glaucoma, and non-arteritic anterior ischemic optic neuropathy (NAION).

Topics: Anti-Bacterial Agents; Continuous Positive Airway Pressure; Elastin; Erythromycin; Eye; Eyelid Diseases; Glaucoma; Humans; Marfan Syndrome; Optic Nerve; Optic Neuropathy, Ischemic; Sleep Apnea, Obstructive

A 17-year-old girl with unilateral congenital glaucoma who had undergone trabeculectomy and peripheral iridectomy in infancy developed apparent exfoliation syndrome (XFS) in the eye that underwent the surgical procedures. A conjunctival biopsy was performed and the specimen was fixed in 2.5% glutaraldehyde, embedded in epoxy resin (Epon-Araldite, Electron Microscopy Sciences, Fort Washington, Pa), and processed for routine electron microscopy and immunostaining for elastin. Results of ultrastructural study showed scattered fibrillar aggregates compatible with those of XFS in an older adult, differing chiefly in sparsity of granular interfibrillar matrix. The XFS fibers were closely associated with elastic fibers and microfibrils. Elastosis of the actinic-aging type was somewhat greater than expected for age. To our knowledge, this is the youngest patient described with characteristic ocular findings of XFS to date, supporting others who have suggested an association between iris surgery in youth and early onset XFS. Electron microscopy was essential in ruling out the possibility of a clinically similar entity caused by ultrastructurally different material.

Topics: Adolescent; Biopsy; Conjunctiva; Elastin; Exfoliation Syndrome; Female; Glaucoma; Humans; Iris; Microscopy, Immunoelectron; Trabeculectomy

Pseudoexfoliation syndrome (PXF) is an idiopathic disease with a high prevalence rate. The elastosis disorder is contributed by genetic and non-genetic factors. Elastin dysregulation associated with the disease mechanism is incompletely understood. This study evaluated the molecules of the elastogenesis machinery in PXF. Lens capsule and aqueous humor (aqH) samples (age/sex-matched) were collected from the eyes with PXF alone and PXF with glaucoma (PXF-G) undergoing Extra Capsular Cataract Extraction (ECCE) surgery. The Elastin turnover was assessed by estimating Desmosine levels in the lens capsules by HPLC analysis. Expression of elastogenesis genes [EMILIN1, CLU, FBN1, FN1, FBLN5, FBLN4 and LOXL1] were evaluated in the lens capsule by qPCR while the proteins were assessed in aqH by western blot analysis. The Desmosine content in the lens capsules were 3-fold and 6-fold elevated in PXF (P = 0.02) and PXF-G (P = 0.01) respectively compared to the cataract-alone, indicating increased elastin degradation. A significant increase in the transcript levels of the CLU, FBLN4, EMILIN1, FBLN5, FN1, FBN1, LOXL1 along with significant changes in protein expression of CLU, FBLN5, FBN1 and LOXL1 signified up-regulation of the elastogenesis machinery. The study provides direct evidence of augmented elastin degradation and turnover in the lens capsule of PXF marked by increased Desmosine content and the expression of proteins involved in mature elastin formation.

Topics: Capsules; Cataract; Desmosine; Elastin; Exfoliation Syndrome; Glaucoma; Humans; Lens Capsule, Crystalline

The trabecular meshwork (TM) consists of extracellular matrix (ECM) with embedded collagen and elastin fibers providing its mechanical support. TM stiffness is considerably higher in glaucoma eyes. Emerging data indicates that the TM moves dynamically with transient intraocular pressure (IOP) fluctuations, implying the viscoelastic mechanical behavior of the TM. However, little is known about TM viscoelastic behavior. We calculated the viscoelastic mechanical properties of the TM in n = 2 healthy and n = 2 glaucoma eyes.. A quadrant of the anterior segment was submerged in a saline bath, and a cannula connected to an adjustable saline reservoir was inserted into Schlemm's canal (SC). A spectral domain-OCT (SD-OCT) provided continuous cross-sectional B-scans of the TM/JCT/SC complex during pressure oscillation from 0 to 30 mmHg at two locations. The TM/JCT/SC complex boundaries were delineated to construct a 20-µm-thick volume finite element (FE) mesh. Pre-tensioned collagen and elastin fibrils were embedded in the model using a mesh-free penalty-based cable-in-solid algorithm. SC pressure was represented by a position- and time-dependent pressure boundary; floating boundary conditions were applied to the other cut edges of the model. An FE-optimization algorithm was used to adjust the ECM/fiber mechanical properties such that the TM/JCT/SC model and SD-OCT imaging data best matched over time.. Significantly larger short- and long-time ECM shear moduli (p = 0.0032), and collagen (1.82x) and elastin (2.72x) fibril elastic moduli (p = 0.0001), were found in the TM of glaucoma eyes compared to healthy controls.. These findings provide additional clarity on the mechanical property differences in healthy and glaucomatous outflow pathway under dynamic loading. Understanding the viscoelastic properties of the TM may serve as a new biomarker in early diagnosis of glaucoma.

Topics: Biomechanical Phenomena; Cross-Sectional Studies; Elastin; Glaucoma; Humans; Trabecular Meshwork

This work focuses on improving the effectiveness of current therapies against glaucoma by incorporating self-assembled polymers into the ophthalmic formulation. To that end, we first studied the influence of the dispersing medium on the mechanical performance of self-assembling elastin-like (EL) and silk-elastin-like (SEL) hydrogels by conducting rheological tests. These polymers were subsequently incorporated into the antiglaucoma formulation, which contains timolol maleate (TM) as active ingredient, and in vivo tests, namely adhesion tests and intraocular pressure measurements (IOP), were performed in New Zealand rabbits. An enhanced reduction in IOP due to the presence of the polymers was observed. Moreover, differences in the effectiveness between both EL- and SEL-hydrogels, which can be explained on the basis of the different rheological properties displayed by these two systems, were also encountered. The results point to the potential of this system as a basis for the development of an ophthalmic formulation against glaucoma.

Topics: Animals; Antihypertensive Agents; Calorimetry, Differential Scanning; Cell Line; Drug Carriers; Drug Liberation; Elastin; Eye; Fibroblasts; Glaucoma; Humans; Hydrogels; Intraocular Pressure; Male; Models, Animal; Ophthalmic Solutions; Rabbits; Rheology; Silk; Timolol; Treatment Outcome

The purpose of this research was to study the effects of age and genetic alterations in key connective tissue proteins on susceptibility to experimental glaucoma in mice. We used mice haploinsufficient in the elastin gene (EH) and mice without both alleles of the fibromodulin gene (FM KO) and their wild type (WT) littermates of B6 and CD1 strains, respectively. FM KO mice were tested at two ages: 2 months and 12 months. Intraocular pressure (IOP) was measured by Tonolab tonometer, axial lengths and widths measured by digital caliper post-enucleation, and chronic glaucoma damage was measured using a bead injection model and optic nerve axon counts. IOP in EH mice was not significantly different from WT, but FM KO were slightly lower than their controls (p = 0.04). Loss of retinal ganglion cell (RGC) axons was somewhat, but not significantly greater in young EH and younger or older FM KO strains than in age-matched controls (p = 0.48, 0.34, 0.20, respectively, multivariable regression adjusting for IOP exposure). Older CD1 mice lost significantly more RGC axons than younger CD1 (p = 0.01, multivariable regression). The CD1 mouse strain showed age-dependence of experimental glaucoma damage to RGC in the opposite, and more expected, direction than in B6 mice in which older mice are more resistant to damage. Genetic alteration in two genes that are constituents of sclera, fibromodulin and elastin do not significantly affect RGC loss.

Topics: Aging; Animals; Axons; Biomechanical Phenomena; Cell Count; Connective Tissue; Disease Models, Animal; DNA; Elastin; Extracellular Matrix Proteins; Eye Proteins; Fibromodulin; Genetic Predisposition to Disease; Glaucoma; Intraocular Pressure; Mice; Mice, Knockout; Mutation; Optic Nerve; Proteoglycans; Retinal Ganglion Cells; Sclera

To evaluate the elastin gene (ELN) as a secondary risk factor for pseudoexfoliation syndrome (PXFS) and the associated glaucoma pseudoexfoliation glaucoma (PXFG).. One hundred seventy-eight unrelated patients with PXFS, including 132 patients with PXFG, and 113 unrelated controls were recruited from the Massachusetts Eye and Ear Infirmary. All the patients and controls were white of European ancestry. Three tag SNPs (rs2071307, rs3823879, and rs3757587) that capture the majority of alleles in ELN were genotyped. Single-SNP association was analyzed using Fisher exact test. Haplotype analysis and the set-based test were used to assess the association for the whole gene. Interaction analysis was done between the ELN SNP rs2071307 and LOXL1 SNP rs2165241 using logistic regression. Multiple comparisons were corrected using the Bonferroni method.. All 3 ELN tag SNPs were not significantly associated with PXFS and PXFG (P>0.20). The minor allele frequencies in PXFS, PXFG, and controls were 40.7%, 39.8%, and 45.6%, respectively for rs2071307, 6.7%, 6.3%, and 5.4% for rs3823879, and 14.8%, 16.2%, and 13.6% for rs3757587. Haplotype analysis and the set-based test did not find significant association of ELN with PXFS (P=0.94 and 0.99, respectively). No significant interaction effects on PXFS were identified between the ELN and LOXL1 SNPs (P=0.55).. Our results suggest that common polymorphisms of ELN are not associated with PXFS and PXFG in white populations. Further studies are required to identify secondary genetic factors that contribute to PXFS.

Topics: Aged; Aged, 80 and over; Elastin; Exfoliation Syndrome; Female; Gene Frequency; Genotype; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors

The characteristic cupping of the optic nerve head (ONH) in glaucoma is associated with elevated TGF-beta2 and increased synthesis and deposition of extracellular matrix (ECM) proteins. In addition to TGF-beta2, the human ONH also expresses bone morphogenetic proteins (BMPs) and BMP receptors, which are members of the TGF-beta superfamily. We examined the potential effects of BMP4 and the BMP antagonist gremlin on TGF-beta2 induction of ECM proteins in ONH cells. BMP-4 dose dependently inhibited TGF-beta2-induced fibronectin (FN) and PAI-1 expression in ONH astrocytes and lamina cribrosa (LC) cells and also reduced TGF-beta2 stimulation of collagen I, collagen VI, and elastin. Addition of gremlin blocked this BMP-4 response, increasing cellular and secreted FN as well as PAI-1 levels in both cell types. Gremlin was expressed in ONH tissues and ONH cells, and gremlin protein levels were significantly increased in the LC region of human glaucomatous ONH tissues. Interestingly, recombinant gremlin dose dependently increased ECM protein expression in cultured ONH astrocytes and LC cells. Gremlin stimulation of ECM required activation of TGF-beta receptor and R-Smad3. TGF-beta2 increased gremlin mRNA expression and protein levels in ONH cells. Inhibition of either the type I TGF-beta receptor or Smad3 phosphorylation blocked TGF-beta2-induced gremlin expression. In conclusion, BMP4 blocked the TGF-beta2 induction of ECM proteins in ONH cells. The BMP antagonist gremlin reversed this inhibition, allowing TGF-beta2 stimulation of ECM synthesis. Increased expression of gremlin in the glaucomatous ONH may further exacerbate TGF-beta2 effects on ONH ECM metabolism by inhibiting BMP-4 antagonism of TGF-beta2 signaling. Modulation of the ECM via gremlin provides a novel therapeutic target for glaucoma.

Topics: Aged; Aged, 80 and over; Astrocytes; Bone Morphogenetic Protein 4; Cell Line; Cell Line, Tumor; Collagen; Elastin; Extracellular Matrix Proteins; Fibronectins; Gene Expression; Glaucoma; Humans; Intercellular Signaling Peptides and Proteins; Optic Disk; Phosphorylation; Plasminogen Activator Inhibitor 1; Receptors, Transforming Growth Factor beta; RNA, Messenger; Smad3 Protein; Transforming Growth Factor beta2

To determine whether abnormal elastin synthesis in the glaucomatous optic nerve head and lamina cribrosa is due to elevated intraocular pressure (IOP) or secondary to axonal injury, monkeys with elevated IOP and with optic nerve transection were compared.. Unilateral, chronic elevated IOP was induced in 11 rhesus monkeys by laser scarification of the trabecular meshwork. IOP was monitored weekly and maintained within 25 to 45 mm Hg for 7 to 36 weeks. In 6 monkeys, unilateral, optic nerve transection was performed, and monkeys were killed after 4 weeks. Optic nerve damage was assessed by stereoscopic slit-lamp biomicroscopy and fundus photography and by confocal scanning laser ophthalmoscopy. The eyes were enucleated and processed for immunohistochemistry and in situ hybridization and for electron microscopic immunogold detection of elastin. Axonal loss was evaluated in cross sections of the optic nerve stained with phenylenediamine.. Compared with normal contralateral controls, the lamina cribrosa of eyes with elevated IOP exhibited markedly increased elastin and the presence of elastotic aggregates in the extracellular matrix and upregulation of elastin mRNA in the astrocytes. In transected eyes, elastin appeared as fine fibers in the lamina cribrosa, without elastotic aggregates, and without new synthesis or abnormal deposition of elastin. At the transected site, new synthesis of elastin was present in the pia mater but not in astrocytes in the glial scar.. This study demonstrates that abnormal elastin synthesis in experimental glaucomatous optic neuropathy in the monkey is specific to elevated IOP and not secondary to axonal loss. The mechanisms by which elevated IOP induces enhanced elastin synthesis in laminar astrocytes are unknown but differ from those involved in acute axonal injury such as transection, where inflammation and breakdown of the blood-nerve barrier occur.

Topics: Animals; Antibodies, Monoclonal; Astrocytes; Elastin; Extracellular Matrix; Female; Fluorescent Antibody Technique, Indirect; Glaucoma; Glial Fibrillary Acidic Protein; In Situ Hybridization; Intraocular Pressure; Macaca mulatta; Male; Ocular Hypertension; Optic Disk; Optic Nerve; Optic Nerve Injuries; RNA, Messenger; Up-Regulation

The purpose of this study was to determine whether elastotic degeneration of the elastin component of the lamina cribrosa occurs in optic neuropathy associated with different types of glaucoma. Human optic nerve heads with primary open-angle, neovascular, chronic angle closure and pseudoexfoliation glaucoma, and with varying duration of disease were compared with age-matched normal eyes, using electron microscopy and immunogold labeling of elastin. The percent area occupied by immunogold-labeled elastin material was determined using a digital image analysis system. In all eyes with a history of glaucoma, elastosis was found in the lamina cribrosa and there was a significantly greater percentage of area occupied by elastin compared with age-matched control eyes (P<0.0001). Among the glaucomatous eyes, pseudoexfoliation glaucoma had the largest area of elastosis, followed by primary open-angle and secondary glaucoma (neovascular and chronic angle closure). In all glaucoma samples, large, confluent elastin aggregates of irregular and varied shapes (elastosis) were observed in the lamina cribrosa and insertion region. These results demonstrate that glaucomatous optic neuropathy is associated with elastosis of the lamina cribrosa, which may contribute to the changes in compliance of the optic nerve heads of glaucomatous eyes.

Topics: Aged; Aged, 80 and over; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Glaucoma; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Optic Disk; Optic Nerve Diseases; Sclera

Pseudoexfoliation syndrome is characterized by the presence of glycoprotein fibers in ocular and extraocular tissues, and often is associated with glaucoma. Pseudoexfoliation material may be associated closely with elastic microfibrillar-associated glycoprotein as well as elastin.. Four optic nerve heads of two patients with pseudoexfoliation syndrome and glaucoma were examined using electron microscopy and immunogold detection of elastin. Optic nerve heads from healthy age-matched individuals and patients with primary open-angle glaucoma were used for comparisons.. In all eyes with pseudoexfoliation and glaucoma, there was marked and widespread elastosis in the connective tissue of the lamina cribrosa. Elastotic fibers appeared as large and irregular aggregates of electron-dense material labeled with anti-elastin antibody. Abundant microfibrils were interspersed in the elastotic aggregates, whereas no typical pseudoexfoliation fibers were observed. In contrast, there were less elastotic fibers in the lamina cribrosa from patients with primary open-angle glaucoma compared with pseudoexfoliation glaucoma. Other changes of extracellular matrix were similar to those observed in primary open-angle glaucoma: decreases in collagen fiber density, presence of basement membranes not associated with cell surfaces, and abundant bundles of microfibrils not labeled with elastin antibody. The elastic fibers appeared normal in other locations within the optic nerves of patients with pseudoexfoliation glaucoma, including in the pial septa and blood vessels of the retrolaminar myelinated optic nerve.. The authors' findings demonstrate marked and site-specific elastosis in the lamina cribrosa of patients with pseudoexfoliation syndrome with glaucoma, suggesting an abnormal regulation of elastin synthesis and/or degradation in the optic nerve of patients with this disease.

Topics: Aged; Connective Tissue; Elastic Tissue; Elastin; Exfoliation Syndrome; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Immunohistochemistry; Male; Microscopy, Immunoelectron; Optic Disk; Sclera

The aim of this study was to determine the location of elastin in the pseudoexfoliative material (PSX) in trabecular tissue of pseudoexfoliation (PE) glaucoma and to estimate the influence of porcine pancreatic elastase-1 (PPE) on elastin in PSX. Trabecular tissue obtained from trabeculectomy specimens of PE glaucoma were used. The tissues were embedded in Lowicryl K4M and sectioned for electron microscopy. First, the sections were subjected to protein A-gold immunohistochemical staining to determine the location of elastin in the tissues. Second, the sections were exposed to PPE, before immunostaining, to evaluate the change of immunolocalization of the gold particles in the tissue. The results were as follows. The gold particles indicating the presence of elastin were located in the PSX as well as in elastic fibers. The density of gold particles in PSX was reduced by PPE. These results show that elastin is located in PSX in trabecular tissue of PE glaucoma, and that PPE dissolves the elastin in PSX.

Topics: Aged; Aged, 80 and over; Animals; Elastin; Exfoliation Syndrome; Glaucoma; Humans; Immunohistochemistry; Pancreatic Elastase; Swine; Trabecular Meshwork

The extracellular materials (ECMs) in the trabecular meshwork (TM) are thought to play a crucial role in aqueous outflow resistance. Immunohistochemical localization of elastin, one of the major ECMs in the normal and glaucomatous human TM, was examined ultrastructurally.. Eight normal eye bank eyes and 16 trabeculectomy specimens of primary open angle glaucoma (POAG, 11 eyes from 8 cases), congenital glaucoma (2 eyes from 1 case), and juvenile glaucoma (3 eyes from 2 cases) were embedded in Lowicryl K4M at low temperature. The distribution of elastin was studied by the protein A-gold technique.. In normals, the gold particles indicating the antigenic sites for elastin existed mainly in the central amorphous element of the elastic-like fibers, and a few gold particles were observed within the area containing fine granular-like material and fine fibrillar-like material. No labeling was observed in cellular materials or other ECMs. In congenital and juvenile glaucoma, labeling was similar to that observed in normals. In POAG specimens compared to normals, there was an increased amount of elastin-bound immunogold particles along the inner canal endothelium. The increased gold particles, which did not have a fibrillar arrangement and were not enclosed by electron-dense microfibrils, were found within the area containing fine fibrillar-like material. However, labeling within the elastic-like fibers was similar to that observed in normals.. Under electron microscopy, elastin could be localized in the normal and glaucomatous human TM. The results of this investigation suggest that elastin may play an important role in the etiology of POAG.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Proteins; Child, Preschool; Elastin; Glaucoma; Glaucoma, Open-Angle; Gold Colloid; Humans; Immunohistochemistry; Microscopy, Immunoelectron; Middle Aged; Trabecular Meshwork; Trabeculectomy

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Anterior Eye Segment; Child; Child, Preschool; Collagen; Elastin; Glaucoma; Glaucoma, Open-Angle; Humans; Infant; Intraocular Pressure; Macaca; Male; Middle Aged; Optic Nerve; Proteoglycans

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.

Topics: Animals; Chronic Disease; Collagen; Disease Models, Animal; Elastin; Extracellular Matrix; Fundus Oculi; Glaucoma; Immunoenzyme Techniques; Intraocular Pressure; Laminin; Laser Therapy; Macaca fascicularis; Optic Disk

Microfibrils in the connective tissue can be subdivided into two classes, elastin-associated and elastin-independent microfibrils. The distribution of microfibrils of both classes were studied in the anterior segment of the human ocular tissues, with a view to examine age-related morphological changes. In the trabecular meshwork of infants, the tubular structure of microfibrils was identified and the fibrils were associated with elastin, forming a typical elastic fiber. This was confirmed by the tannic acid-uranyl acetate staining which reacts specifically with elastin. In the cornea, microfibrils were detected in the deep stroma of the infant. They were not associated with elastin (elastin-independent microfibrils). In the glaucomatous eye of a 7-year-old boy, microfibrils were indistinct in the trabecular meshwork. In the corneal stroma of the same eye, microfibrils were observed, but the occurrence was rarer than in the nonglaucomatous infants examined in this study. In the trabecular meshwork of aged persons, no tubular or fibrillar structure was seen around the elastin. Microfibrils were not observed in the cornea. The morphological features and occurrence of microfibrils change with age in the anterior segment of the human eye. Thus microfibrils can be a good indicator for the age-related changes in these tissues.

Topics: Actin Cytoskeleton; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Child; Connective Tissue; Corneal Stroma; Elastic Tissue; Elastin; Female; Glaucoma; Humans; Infant; Male; Middle Aged; Trabecular Meshwork

Quantitative studies of collagen density and fibril size distribution as well as elastin density were carried out in the optic nerve head and sclera of human and experimental monkey glaucoma eyes. The collagen fibrils of the normal lamina cribrosa are smaller and more uniform in size than those of the sclera. This feature may be an adaptation to maximize either elasticity or resistance to mechanical stress. In glaucomatous nerve heads, there is a major disruption of the structure of the lamina cribrosa beam structure, including a decrease in collagen density. The peripapillary sclera undergoes similar collagen density changes to those in the nerve head in human glaucoma eyes. Elastin fiber density is unchanged in the glaucomatous nerve heads that we studied.

Topics: Aged; Aged, 80 and over; Animals; Cell Count; Collagen; Elastin; Female; Glaucoma; Humans; Intraocular Pressure; Macaca fascicularis; Male; Middle Aged; Optic Disk; Photography; Sclera

The changes of immunoreactivity and immunolocalization of the extracellular matrices (ECM), collagen type I through VI, laminin, fibronectin and alpha-elastin, of optic nerve lamina cribrosa in argon laser induced glaucoma in monkey eyes were examined using a immunohistochemical method, biotin-streptavidin system. The results were consistent with the previous findings that in the experimental glaucoma eyes, diffuse immunoreactivity of collagen type I, III, V, VI, fibronectin were detected in the thickened and irregular laminar beams, while linear staining for collagen type IV and laminin were seen around the laminar beams and vascular walls were densely, thickly and irregularly, and furthermore immunoreactivity for alpha-elastin was reduced markedly in the glial columns and moderately in the lamina cribrosa. In the lamina cribrosa with optic disc cupping in laser-induced monkey glaucoma, the immunoreactivity for alpha-elastin was changed most greatly, and no qualitative differences were detected in comparison with normal fellow eyes for the other ECM components.

Topics: Animals; Collagen; Elastin; Extracellular Matrix; Fibronectins; Glaucoma; Immunohistochemistry; Laminin; Macaca fascicularis; Optic Nerve

The optic nerve heads from normal and glaucomatous eyes of humans and monkeys were examined by light and electron microscopy for the presence and distribution of elastin. Elastin densely lined the insertion of the lamina cribrosa into the sclera and was prominent in the laminar beams. The long axis of elastin paralleled that of the collagen fibrils and corresponded to the directions of expected forces on the tissue. In glaucomatous eyes elastin molecules were curled instead of straight and seemed disconnected from the other elements of the connective tissue matrix. Laminar beams stretch and reorganise their substructure during glaucomatous atrophy, probably leading to changed compliance. Differences in elastin function may have a part in susceptibility to glaucomatous injury.

Topics: Aged; Animals; Collagen; Elastin; Female; Glaucoma; Histocytochemistry; Humans; Macaca fascicularis; Male; Microscopy, Electron; Optic Disk

Topics: Aged; Anterior Chamber; Collagen; Elastin; Glaucoma; Humans; Middle Aged; Trabecular Meshwork