elastin and Exfoliation-Syndrome

The genetic basis of pseudoexfoliation (PEX) syndrome, the most common identifiable cause of open-angle glaucoma, is steadily being elucidated. This review summarizes the recent advances on genetic risk factors for PEX syndrome/glaucoma and their potential functional implications in PEX pathophysiology.. As of today, seven loci associated with the risk of PEX surpassing genome-wide significance have been identified by well-powered genome-wide association studies and sequencing efforts. LOXL1 (lysyl oxidase-like 1) represents the major genetic effect locus, although the biological role of common risk variants and their reversed effect in different ethnicities remain an unresolved problem. Rare protein-coding variants at LOXL1 and a single noncoding variant downstream of LOXL1 showed no allele effect reversal and suggested potential roles for elastin homeostasis and vitamin A metabolism in PEX pathogenesis. Other PEX-associated genetic variants provided biological insights into additional disease processes and pathways, including ubiquitin-proteasome function, calcium signaling, and lipid biosynthesis. Gene-environment interactions, epigenetic alterations, and integration of multiomics data have further contributed to our knowledge of the complex etiology underlying PEX syndrome and glaucoma.. PEX-associated genes are beginning to reveal relevant biological pathways and processes involved in disease development. To understand the functional consequences and molecular mechanisms of these loci and to translate them into novel therapeutic approaches are the major challenges for the future.

Topics: Amino Acid Oxidoreductases; Elastin; Exfoliation Syndrome; Genetic Predisposition to Disease; Genome-Wide Association Study; Glaucoma, Open-Angle; Humans; Polymorphism, Single Nucleotide; Risk Factors; Vitamin A

Several lines of evidence, such as ultrastructural signs for activated fibrillogenesis and excessive production of elastic microfibrillar components in the anterior segment of the eye and throughout the body, indicate that exfoliation syndrome (XFS) is an elastic microfibrillopathy, leading to the accumulation of an abnormal extracellular fibrillar material (XFM). The upregulation of elastic microfibrillar components is paralleled by the selective upregulation of the cross-linking enzyme lysyl oxidase-like 1 (LOXL1) in the early phase of the disease, suggesting that LOXL1 participates in the stabilization of newly synthesized elastic proteins and finally in the stable accumulation of XFM. Whereas the excessive production of elastic proteins rises from early to late XFS stages, possibly mediated by increasing fibrogenic stimuli in the aqueous humor, LOXL1 is downregulated in late stages of the disease by as yet unknown mechanisms, possibly leading to the well-documented elastotic matrix alterations characteristic of eyes with late stage XFS. Several studies indicate complex changes of the proteolytic balance in the anterior segment of XFS eyes, characterized primarily by decreased matrix metalloproteinase-2 activity, the major aqueous matrix metalloproteinase, potentially leading to a shift from appropriate matrix turnover to progressive matrix accumulation. In contrast, in nearly all tissues of the posterior segment, XFM seems to be absent and differential gene expression is confined to the lamina cribrosa, characterized by a stage-independent, primary, and XFS-specific downregulation of LOXL1 and elastic components in XFS eyes. Concomitant with this deficiency, the laminar elastic fiber network displays prominent ultrastructural alterations, which may lead to increased vulnerability to glaucomatous damage. Various growth factors, stress conditions, or dietary factors have been supposed to potentially influence the manifestation of the disease. However, in spite of increasing knowledge, the pathogenetic factors initiating the abnormal matrix process still remain elusive. Such information would be critical for our understanding of disease progression and would disclose new options for pharmaceutical intervention at the onset of the disease.

Topics: Anterior Eye Segment; Elastin; Exfoliation Syndrome; Extracellular Matrix; Extracellular Matrix Proteins; Glaucoma, Open-Angle; Humans; Microfibrils

The Utah Project on Exfoliation Syndrome (UPEXS) study was created to investigate the association between exfoliation syndrome (XFS) and systemic disorders or pathologies. The study utilizes the resources of the Utah Population Database, which is linked to the Utah genealogy, a compilation of large pedigrees extending back 3 to ≥11 generations, representing most families in the state. These family members medical and health records are linked to vital records and can be used effectively to identify familial clustering of disorders, like XFS, with comorbid diseases or health-related data. There is growing evidence that XFS patients have an increased risk for systemic disorders that may reflect the systemic tissue involvement of this disease. Epidemiologic studies of individuals with XFS have reported an increased risk of various pathologies that have abnormalities in extracellular matrix metabolism and repair. For this reason, the UPEXS has focused on disorders that involve the extracellular matrix in general and elastin specifically, such as pelvic organ prolapse, atrial fibrillation, inguinal hernias, and chronic obstructive pulmonary disease. In this paper we present our results from the analysis of pelvic organ prolapse, as well as, preliminary data for atrial fibrillation.

Topics: Atrial Fibrillation; Databases, Factual; Elastin; Exfoliation Syndrome; Extracellular Matrix; Humans; Intraocular Pressure; Pelvic Organ Prolapse; Utah

Pseudoexfoliation syndrome (PXS) is a systemic condition with eye manifestations. In the eye, pseudoexfoliation material deposits on various structures of the anterior segment. The nature of this material is mostly fibrillar with fibers made up of microfibrils and coated with amorphous material. The composition of these fibrils is diverse and includes basement membrane components as well as enzymes involved in extracellular matrix maintenance. Pseudoexfoliation is the most common cause of secondary open-angle glaucoma (pseudoexfoliation glaucoma, PXG) worldwide. The goal of this review is to summarize our knowledge on the genetics of this systemic disorder and its resultant ocular manifestations. PXS familial aggregation suggests genetic inheritance. PXS has been strongly associated with single nucleotide polymorphisms (SNPs) of the lysyl oxidase-like 1 (LOXL1) gene on chromosome 15q24.1. Two of these SNPs confer a higher than 99% population attributable risk for PXS and PXG in the Nordic population; however, they carry different risks in different populations. The high risk haplotypes also vary among different populations. LOXL1 is one of group of the enzymes involved in the cross-linking of collagen and elastin in the extracellular matrix. Its function in connective tissue maintenance has been confirmed in mice; however, its actual role in PXS remains unclear. Contactin-associated protein-like 2 also has a strong genetic association with PXS in a German cohort and is an attractive candidate molecule. It encodes for a protein involved in potassium channel trafficking. Other candidate genes linked to PXS include lysosomal trafficking regulator, clusterin, adenosine receptors, matrix metalloproteinase-1 (MMP1), and glutathione transferase. These genes may be modifying genes for development of PXS and PXG.

Topics: Amino Acid Oxidoreductases; Chromosomes, Human, Pair 15; Clusterin; Collagen; Elastin; Exfoliation Syndrome; Extracellular Matrix; Eye; Gene-Environment Interaction; Glaucoma, Open-Angle; Glutathione Transferase; Haplotypes; Humans; Matrix Metalloproteinase 1; Polymorphism, Single Nucleotide; Receptor, Adenosine A3

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

Pseudoexfoliation syndrome (PXF) is an idiopathic, elastogenesis-associated systemic disease characterised by amyloid-like material aggregates in the eye. Elevated plasma and aqueous humour (aqH) homocysteine (Hcy) is reportedly associated with PXF. This study is aimed to probe Hcy-mediated alterations in elastin expression.. Lens level of Hcy (total Hcy (tHcy)), mRNA expression of. The lens tHcy was significantly high in PXF (p=0.02) and PXF-G (p=0.009).. The study reveals that lens accumulation of Hcy associated with hyperhomocysteinaemia is characteristic of PXF that augments elastin expression. Hcy causes structural changes promoting elastin aggregation, thereby contributing to defective elastin in PXF and PXF-G.

Topics: Aqueous Humor; Blotting, Western; Elastin; Exfoliation Syndrome; Gene Expression Regulation; Homocysteine; Humans; Intraocular Pressure; Lens, Crystalline; Prospective Studies; RNA

Fibulin-5 (FBLN5), an extracellular scaffold protein, plays a crucial role in the activation of Lysyl oxidase like-1 (LOXL1), a tropoelastin crosslinking enzyme, and subsequent deposition of elastin in the extracellular matrix. Following study identifies polymorphisms within FBLN5 gene as risk factors and its aberrant expression in the pathogenesis of an ocular disorder, pseudoexfoliation (PEX). Exons and exon-intron boundaries within FBLN5 gene were scanned through fluorescence-based capillary electrophoresis for polymorphisms as risk factors for PEX pathogenesis in recruited study subjects with Indian ethnicity. mRNA and protein expression of FBLN5 was checked in lens capsule of study subjects through qRT-PCR and western blotting, respectively. In vitro functional analysis of risk variants was done through luciferase reporter assays. Thirty study subjects from control and PEX affected groups were scanned for potential risk variants. Putative polymorphisms identified by scanning were further evaluated for genetic association in a larger sample size comprising of 338 control and 375 PEX affected subjects. Two noncoding polymorphisms, hg38 chr14:g.91947643G>A (rs7149187:G>A) and hg38 chr14:g.91870431T>C (rs929608:T>C) within FBLN5 gene are found to be significantly associated with PEX as risk factors with a p-value of 0.005 and 0.004, respectively. Molecular assays showed a decreased expression of FBLN5 at both mRNA and protein level in lens capsule of pseudoexfoliation syndrome (PEXS) affected subjects than control. This study unravels two novel risk variants within FBLN5 gene in the pathogenesis of PEX. Further, a decreased expression of FBLN5 in PEXS affected lens capsules implicates a pathogenic link between extracellular matrix maintenance and onset of PEX.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Oxidoreductases; Elastin; Exfoliation Syndrome; Extracellular Matrix; Extracellular Matrix Proteins; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Lens Capsule, Crystalline; Male; Middle Aged; Polymorphism, Single Nucleotide

Exfoliation syndrome (ES) is commonly associated with glaucoma, premature cataracts, and other ocular and systemic pathologies. LOXL1 gene variants are significantly associated with ES; however, the role of the protein in ES development remains unclear. The purpose of this study was to characterize the ocular phenotype in Loxl1(-/-) (null) mice.. Loxl1 null mice and strain-matched controls (C57BL) were evaluated by clinical and histologic analyses.. Anterior segment histology showed a pronounced vesiculation of the anterior lens in the null mice. The lesions were subcapsular and in direct apposition with the posterior iris surface. Fluorescein angiography showed increased diffusion of fluorescein into the anterior chamber of the null mice compared with age-matched controls (P = 0.003, two-tailed, unequal variance t-test), suggesting compromise of the blood-aqueous barrier. Intraocular pressure measurements were within the normal range (16.5 ± 2.0 mm Hg) in null mice up to 1 year of age. Immunohistochemistry showed decreased elastin in the iris and ciliary body in the null mouse compared with controls.. Elimination of LOXL1 in mice impairs the blood-aqueous humor barrier in the ocular anterior segment and causes lens abnormalities consistent with cataract formation, but does not result in deposition of macromolecular material or glaucoma. These results show that mice lacking LOXL1 have some ES features but that complete disease manifestation requires other factors that could be genetic and/or environmental.

Topics: Amino Acid Oxidoreductases; Animals; Anterior Chamber; Blood-Aqueous Barrier; Cataract; Ciliary Body; Elastin; Exfoliation Syndrome; Fluorescein; Fluorescein Angiography; Fluorescent Antibody Technique, Indirect; Fluorescent Dyes; Gene Expression Regulation, Enzymologic; Immunoblotting; Intraocular Pressure; Iris; Lens, Crystalline; Mice; Mice, Inbred C57BL; Microscopy, Immunoelectron; Phenotype; Polymerase Chain Reaction

To test the hypothesis that a primary disturbance in lysyl oxidase-like 1 (LOXL1) and elastin metabolism in the lamina cribrosa of eyes with pseudoexfoliation syndrome constitutes an independent risk factor for glaucoma development and progression.. Observational, consecutive case series.. Posterior segment tissues obtained from 37 donors with early and late stages of pseudoexfoliation syndrome without glaucoma, 37 normal age-matched control subjects, 5 eyes with pseudoexfoliation-associated open-angle glaucoma, and 5 eyes with primary open-angle glaucoma (POAG).. Protein and mRNA expression of major elastic fiber components (elastin, fibrillin-1, fibulin-4), collagens (types I, III, and IV), and lysyl oxidase crosslinking enzymes (LOX, LOXL1, LOXL2) were assessed in situ by quantitative real-time polymerase chain reaction, (immuno)histochemistry, and light and electron microscopy. Lysyl oxidase-dependent elastin fiber assembly was assessed by primary optic nerve head astrocytes in vitro.. Expression levels of elastic proteins, collagens, and lysyl oxidases in the lamina cribrosa.. Lysyl oxidase-like 1 proved to be the major lysyl oxidase isoform in the normal lamina cribrosa in association with a complex elastic fiber network. Compared with normal and POAG specimens, lamina cribrosa tissues obtained from early and late stages of pseudoexfoliation syndrome without and with glaucoma consistently revealed a significant coordinated downregulation of LOXL1 and elastic fiber constituents on mRNA and protein level. In contrast, expression levels of collagens and other lysyl oxidase isoforms were not affected. Dysregulated expression of LOXL1 and elastic proteins was associated with pronounced (ultra)structural alterations of the elastic fiber network in the laminar beams of pseudoexfoliation syndrome eyes. Inhibition of LOXL1 interfered with elastic fiber assembly by optic nerve head astrocytes in vitro.. The findings provide evidence for a pseudoexfoliation-specific elastinopathy of the lamina cribrosa resulting from a primary disturbance in LOXL1 regulation and elastic fiber homeostasis, possibly rendering pseudoexfoliation syndrome eyes more vulnerable to pressure-induced optic nerve damage and glaucoma development and progression.

Topics: Aged; Aged, 80 and over; Amino Acid Oxidoreductases; Aminopropionitrile; Astrocytes; Cells, Cultured; Collagen; Disease Progression; Disease Susceptibility; Elastic Tissue; Elastin; Enzyme Inhibitors; Exfoliation Syndrome; Extracellular Matrix; Extracellular Matrix Proteins; Female; Fibrillin-1; Fibrillins; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation, Enzymologic; Glaucoma, Open-Angle; Humans; Male; Microfilament Proteins; Optic Disk; Real-Time Polymerase Chain Reaction; Risk Factors; Tissue Donors; Transforming Growth Factor beta1

Pseudoexfoliation (PEX) syndrome/glaucoma is a complex, late-onset disorder of the elastic fiber system. Strong genetic risk is conferred by the lysyl oxidase-like 1 (LOXL1) gene, but additional comodulating factors are necessary for the manifestation of the disease. The aim of this study was to analyze the effect of various PEX-associated pathogenic factors on the genotype-correlated expression of LOXL1 and elastin-related genes.. Cultured human Tenon's capsule fibroblasts with high- and low-risk LOXL1 haplotypes were exposed to transforming growth factor (TGF)-β1, interleukin (IL)-6, homocysteine, oxidative stress, hypoxia, or ultraviolet (UV) radiation. Changes in the expression of LOXL1 and elastic constituents of PEX material and TGF-β1 were assessed by quantitative real-time PCR, Western blotting, immunohistochemistry, and electron microscopy.. Treatment of fibroblasts with TGF-β1, oxidative stress, UV light, and hypoxia induced a significant increase in expression levels of LOXL1 and elastic proteins, whereas the effect of IL-6 was limited to induction of elastic constituents. Immunohistochemistry and electron microscopy confirmed an upregulation of LOXL1 and elastic fiber proteins and their assembly into extracellular microfibrillar networks with focal aggregation of microfibrils into PEX-like fibrils on stimulation with TGF-β1 and oxidative stress. Basal and stimulated expression of LOXL1 mRNA and protein was slightly decreased in cells carrying the high-risk compared with the low-risk haplotype of LOXL1, but the differences between groups were statistically not significant.. The findings support the notion that both genetic and nongenetic fibrogenic factors, particularly TGF-β1 and oxidative stress, may cooperate in the stable accumulation of PEX aggregates.

Topics: Aged, 80 and over; Amino Acid Oxidoreductases; Blotting, Western; Cells, Cultured; Elastin; Exfoliation Syndrome; Female; Fibroblasts; Gene Expression Regulation; Genotype; Homocysteine; Humans; Hydrogen Peroxide; Immunohistochemistry; Male; Microscopy, Electron; Oxidative Stress; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tenon Capsule; Transforming Growth Factor beta1

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

Exfoliation glaucoma (XFG) is the commonest identifiable cause of secondary open-angle glaucoma worldwide, characterized by the deposition of fibrillar proteins in the anterior segment of the eye. We investigated LOXL1 gene variants previously identified to confer susceptibility to XFG in a Utah Caucasian cohort. After a standard eye examination protocol we genotyped SNPs rs2165241and rs3825942 in 62 XFG or exfoliation syndrome (XFS) patients and 170 normal controls. Genotype frequency distribution, odds ratios (ORs) and population attributable risks were calculated for the risk alleles. The SNP rs2165241 was significantly associated with XFG and XFS (p = 4.13 x 10(-9)) for an additive model, OR(het) = 4.42 (2.30-8.50), OR(hom) = 34.19 (4.48-261.00); T allele: 83.1% in cases versus 52.4% in controls). Significant association was also found for rs3825942: (p = 1.89 x 10(-6)). Our findings confirm genetic association of LOXL1 with XFG and XFS and implicate a potential role of cross linking of elastin in the pathogenesis of XFG. This information will potentially guide glaucoma monitoring efforts by targeting individuals whose genetic profiles put them at higher risk for XFG.

Topics: Amino Acid Oxidoreductases; Cohort Studies; DNA Primers; Elastin; Exfoliation Syndrome; Female; Genetic Predisposition to Disease; Genotype; Glaucoma, Open-Angle; Humans; Male; Odds Ratio; Polymorphism, Single Nucleotide; Utah; White People

Topics: Amino Acid Oxidoreductases; Elastin; Exfoliation Syndrome; Glaucoma, Open-Angle; Humans; Polymorphism, Single Nucleotide

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 present investigation was undertaken to determine if some of the components of exfoliation material in iris tissue were unique to exfoliation or were part of normal iris architecture. Eleven normal iris specimens and 10 exfoliative iris specimens were processed for cryoultramicrotomy and London resin white embedding. Immunogold electron microscopy was used to investigate the fine structural distribution of amyloid P component, elastin, entactin, fibronectin, gp115, and vitronectin in normal iris and their association with exfoliation material. Exfoliation material was positive for amyloid P component and possibly gp115, neither of which were present in normal iris tissue. Elastin and fibronectin were present in the normal iris stroma but were not associated with exfoliation material. The distribution of amyloid P component in the vessel lumen and wall led to the conclusion that amyloid P is a serum contaminant. The presence of gp115 in exfoliation material represents the synthesis of a component novel to the iris vascular cell synthetic repertoire.

Topics: Adult; Aged; Aged, 80 and over; Elastin; Exfoliation Syndrome; Female; Glycoproteins; Humans; Immunohistochemistry; Iris; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Serum Amyloid P-Component; Vitronectin

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