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PubMed1995

Localization and possible gene expression of proteoglycan decorin in the trabecular meshwork.

It is known that trabecular meshwork cells produce proteoglycans and that local production may be associated with aqueous outflow resistance. In an attempt to identify intraocular production of proteoglycan decorin in the anterior chamber angle of mammalian eyes, we conducted a Northern blot analysis and immunohistochemical studies. Northern blot analysis suggested gene expression of proteoglycan decorin in trabecular meshwork cells. Also, immunohistochemical studies using anti-decorin antibody demonstrated decorin-like immunoreactivity in the trabecular meshwork and around the Schlemm's canal. Our data demonstrate the presence of proteoglycan decorin in the outflow pathway, suggesting that decorin is a component of extracellular matrices in these regions and may be associated with outflow resistance.

Animals↗
PubMed2004

Expression of CD44 in cultured human trabecular meshwork cells.

PURPOSE: To determine whether cultured human trabecular meshwork cells express CD44 and to discuss their possible relationship with primary open angle glaucoma. METHODS: Human trabecular meshwork cells were cultured in DMEM/F12 media. Total RNAs from the cells were extracted with Trizol reagent. Messenger RNA expression of CD44 in human trabecular meshwork cells was examined by using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Expression of CD44 was confirmed by Western-blotting and immunofluorescent microscopy. Effect of CD44-specific antisense oligonucleotide on adhesion of trabecular meshwork cells to hyaluronate was determined by MTT assay. RESULTS: A single RT-PCR product whose size was 471 bp was obtained. A band about 80kD was stained by Western-blot. Immunofluorescent examination of expression of CD44 on the cell surface was positive and reactions were mainly localized in cell membranes. Adhesion of trabecular meshwork cells to hyaluronate was inhibited by CD44-specific antisense oligonucleotide. CONCLUSIONS: Cultured human trabecular meshwork cells express CD44. CD44 may play a role in pathogenesis of primary open angle glaucoma.

Cell Adhesion↗
PubMed2002

[Insulin-like growth factor 1 (IGF-1) mRNA and IGF-1 protein. Expression in cells of the trabecular meshwork of the bovine eye].

BACKGROUND: The purpose of the study was to determine whether cultured bovine trabecular meshwork cells and trabecular tissue ex vivo express insulin-like growth factor-1 (IGF-1) mRNA and protein. METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of IGF-1 mRNA. To detect the protein on the cells an IGF-1-specific immunohistochemical stain was used on trabecular meshwork cells. RESULTS: A single 240 bp RT-PCR product was obtained, the RT-PCR product was verified by sequencing and the derived sequence was homologous to the known bovine sequence. IGF-1 immunostaining was positive in the cytoplasm of trabecular meshwork cells. CONCLUSIONS: We conclude that trabecular meshwork cells produce IGF-1 mRNA and contribute to the presence of IGF-1 protein in the trabecular meshwork microenvironment as well as aqueous humor. Trabecular meshwork cells were affected by IGF-1 not only through paracrine but also through autocrine action. Whether regulations in IGF-1 production may contribute to the pathogenesis of primary open-angle glaucoma and the possibility of promoting the autocrine action of IGF-1 by trabecular meshwork cells to treat the disease is worth further investigation.

Animals↗
PubMed2002

Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells.

PURPOSE: Increased fibronectin accumulation in the trabecular meshwork of glaucomatous eyes may contribute to the resistance of aqueous outflow and the development of primary open-angle glaucoma (POAG). Because the glucose level is increased in the aqueous humor of patients with diabetes, this study was conducted to determine whether a high-glucose condition alters fibronectin expression and contributes to cell loss in trabecular meshwork. METHODS: The fibronectin mRNA level was determined using RT-PCR in bovine trabecular meshwork cells grown in normal (5 mM) or high (30 mM)-glucose medium for 7 days, and cell counts were measured during this period. Distribution and the relative amount of fibronectin protein were determined in these cells by immunofluorescence microscopy and Western blot analysis. RESULTS: Fibronectin mRNA level in cells grown in high-glucose medium was significantly upregulated two- to threefold compared with cells grown in normal medium (P < 0.05). In cells grown in high-glucose medium, fibronectin immunofluorescence was more intense, and the relative amount of fibronectin protein was significantly increased (131% +/- 15% of control, P < 0.05) compared with the amount in cells grown in normal medium. A moderate decrease in cell number was observed in cells grown in high-glucose medium (78% +/- 7% of control, P < 0.05) CONCLUSIONS: These findings indicate that a high glucose level in aqueous humor of patients with diabetes may increase fibronectin syntheses and accumulation in trabecular meshwork and accelerate the depletion of trabecular meshwork cells, a characteristic feature of the outflow system in POAG. The striking similarity between high glucose-induced alterations in trabecular meshwork cells and those of vascular endothelial cells may represent a common biochemical link in the pathogenesis of POAG and diabetic microangiopathy.

Animals↗
PubMed1994

Electrophysiological properties of cultured human trabecular meshwork cells.

Previous studies using cultured bovine trabecular meshwork cells demonstrated at least two different cell types which were distinguishable morphologically and electrophysiologically. The purpose of the present study was to evaluate the electrical membrane properties of cultured human trabecular meshwork cells. Seven different human trabecular meshwork cell lines were grown from four different donors. One trabecular meshwork cell line was transformed by microinjection with SV40 DNA. The electrochemical properties of these TM cells were determined by micropuncture with glass microelectrodes. The mean membrane voltage at resting conditions differed between the cell lines (-33.3 to -58.7 mV). Application of 10-mmol l-1 Ba2+ induced repetitive voltage spikes in all cell lines. The voltage transients similar to action potentials were inhibited by nifedipine, but insensitive to tetrodotoxin. Acetylcholine evoked depolarizations in three cell lines which were blocked by atropine. In one cell line isoproterenol caused sustained depolarizations sensitive to metipranolol. All three of the cell lines tested depolarized upon application of the vasoactive peptide endothelin-1. All untransformed cell lines showed voltage spikes typical for smooth muscle cells and functional receptors for endothelin-1 and cholinergic agonists. One out of three cell lines tested possessed beta-adrenergic receptors influencing the membrane voltage.

Acetylcholine↗
PubMed1991

Differential smooth muscle-like contractile properties of trabecular meshwork and ciliary muscle.

The contractile properties of bovine trabecular meshwork and ciliary muscle strips were investigated using an electromagnetic force-length transducer for isometric force measurements. Acetylcholine, pilocarpine and aceclidine administration resulted in dose-dependent contractions of trabecular meshwork and ciliary muscle. Absolute forces were approximately 10 times larger in ciliary muscle than in trabecular meshwork. Maximal force evoked by aceclidine (5 x 10(-5) M), when compared to the pilocarpine (5 x 10(-5) M) response, was significantly higher in trabecular meshwork than in ciliary muscle. The results were 172.5 +/- 12.6% (n = 7) and 138.9 +/- 4.0% (n = 8, P less than 0.05), respectively. Depolarization induced by raised external potassium (120 mM), when compared to the acetylcholine response (10(-3) M), resulted in a small contraction of 19.3 +/- 4.2% in trabecular meshwork (n = 5), and of 59.0 +/- 13.7% in ciliary muscle (n = 4, P less than 0.01). Both responses were inhibited by atropine (10(-5) M). The differential potassium effect may be explained by the large number of cholinergic nerve endings in ciliary muscle as compared to trabecular meshwork tissue. Recently, a dissociation between the effects of aceclidine on outflow resistance and accommodation has been described. Our data are consistent with these observations and provide evidence for a direct role of trabecular meshwork contractility in aqueous outflow regulation.

Acetylcholine↗
PubMed1995

Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions.

The purpose of the present study was to selectively target pigmented trabecular meshwork cells without producing collateral damage to adjacent non-pigmented cells or structures. The ability to selectively target trabecular meshwork cells without coagulation, while preserving the structural integrity of the meshwork, could be a useful approach to study whether the biological response of non-coagulative damage to the trabecular meshwork and trabecular meshwork cells is similar to that seen with coagulative damage to the trabecular meshwork which occurs with argon laser trabeculoplasty. This approach also may be useful to non-invasively deplete trabecular meshwork cells while preserving the structural integrity of the trabecular meshwork in an animal model. A mixed cell culture of pigmented and non-pigmented trabecular meshwork cells were irradiated with Q-switched Nd-YAG and frequency-doubled Nd-YAG lasers, microsound pulsed dye-lasers, and an argon ion laser in order to define a regime where laser absorption would be confined to pigmented trabecular meshwork cells, thereby permitting selective targeting of these cells without producing collateral thermal damage to adjacent non-pigmented cells. Pulse durations ranged from 10 nsec to 0.1 sec. A fluorescent viability/cytotoxicity assay was used to evaluate laser effects and threshold energies, and cells were examined morphologically by light and TEM. Selective targeting of pigmented trabecular meshwork cells was achieved with pulse durations between 10 nsec and 1 microsec and 1 microsec without producing collateral thermal or structural damage to adjacent non-pigmented trabecular meshworks cells when examined by light and transmission electron microscopy. Pulse durations greater than 1 microsec resulted in non-selective killing of non-pigmented trabecular meshwork cells. Threshold radiant exposures were as low as 18 mJ cm-2, and increased at longer wavelengths, longer pulse durations and lower melanin contents within the cells. It is concluded that selective targeting of pigmented trabecular meshwork cells can be achieved using pulsed lasers with low threshold radiant exposures avoiding collateral thermal damage to adjacent non-pigmented trabecular meshwork cells. This approach can be readily applied in vivo.

Cell Survival↗
PubMed2003

Hyaluronan synthase in trabecular meshwork cells.

BACKGROUND/AIMS: Hyaluronan is present in the trabecular meshwork where it is involved in the pathophysiology of aqueous outflow environment. In this study, the expression and regulation of hyaluronan synthase (HAS), which is the enzyme synthesising hyaluronan, in trabecular meshwork cells were investigated. METHODS: Cultured bovine trabecular meshwork cells (BTMCs) were used. HAS expression in BTMCs was examined by RT-PCR. The effects of transforming growth factor beta (TGF-beta) and platelet derived growth factor BB (PDGF-BB) on HAS expression in BTMCs were examined by quantitative RT-PCR. The HAS2 expression by TGF-beta and PDGF-BB at the protein level was also confirmed immunohistochemically. The production of hyaluronan from BTMCs was detected by high performance liquid chromatography (HPLC). RESULTS: Three HAS isoforms were expressed in BTMCs at the mRNA level. Among HAS isoforms, only the expression of HAS2 mRNA was increased by the administration of TGF-beta or PDGF-BB. HAS2 upregulation by these growth factors was also confirmed at the protein level. Further, hyaluronan production from BTMCs was stimulated by TGF-beta or PDGF-BB. CONCLUSION: Expression of HAS in trabecular meshwork may maintain the hyaluronan content in the aqueous outflow pathway. Its production is regulated by TGF-beta and PDGF-BB. The regulation of the expression of HAS in trabecular meshwork might be useful for modulating the aqueous outflow environment.

Animals↗
PubMed1997

[The expression of EGF mRNA and EGF receptors in human trabecular meshwork cells in vitro].

OBJECTIVE: To demonstrate that cultured trabecular meshwork cells can secrete epidermal growth factor (EGF) and there are EGF receptors (EGFRs) on the cells. METHODS: Human trabecular meshwork cells were cultured in vitro and passaged 3-5 times. Immunohistochemical stain was used to detect EGFRs on the trabecular meshwork cell membrane. EGF cDNA probe, alpha-32P isotope labeling and dot blot hybridization autoradiographic method were used to detect EGF mRNA in the cells. RESULTS: Cultured human trabecular meshwork cells were obtained. EGFR immunostain was positive, and the reaction of brown color was at the surface of the cells. Dot blot hybridization autoradiography showed that trabecular cells can express EGF mRNA. CONCLUSIONS: Trabecular meshwork cells can secrete EGF. There are EGFRs on the membrane of trabecular meshwork cells. It is suggested that probably up-regulating the receptors or promoting the cells to secrete growth factors have potential significance in the regeneration of trabecular cells and recovery of the cell functions in open angle glaucoma.

Adolescent↗
PubMed1999

Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells.

PURPOSE: To characterize cyclic nucleotide phosphodiesterase isozyme activities in human trabecular meshwork cells and primary cultures of porcine trabecular meshwork cells. METHODS: Radioimmunoassay of acetylated acid extracts was used to determine changes in cyclic adenosine monophosphate (cAMP) and cyclic quanosine monophosphate (cGMP) in human trabecular meshwork cells treated with phosphodiesterase isoform selective inhibitors. Cyclic nucleotide phosphodiesterase activities were measured using the two-step radioisotope procedure (Thompson). Enzyme activities in the supernatant of human cells were fractionated using anion-exchange chromatography. Additionally, human and porcine trabecular meshwork cell transcripts of phosphodiesterase family-specific isoforms were studied by reverse transcription-polymerase chain reaction and nucleotide sequencing. RESULTS: In intact human cells, selective inhibitors for phosphodiesterase 4 (rolipram) and 5 (E4021) gene families were effective in augmenting cyclic nucleotide accumulation in response to isoproterenol or sodium nitroprusside, respectively. cAMP and cGMP hydrolytic activities, resolved using Trisacryl M anion-exchange chromatography, showed a cAMP phosphodiesterase peak that was minimally sensitivity to cGMP but modestly inhibited by rolipram and a cGMP phosphodiesterase peak that was sensitive to inhibition by E4021. Further evaluation of the cGMP phosphodiesterase demonstrated Michaelis-Menten kinetics and competitive inhibition by E4021. Messenger RNA transcripts for phosphodiesterase 4, 5, and 7 isozymes were isolated in human trabecular meshwork cells. However, in porcine trabecular meshwork cells only isozymes for phosphodiesterase 4 and 5 isozymes were detected. CONCLUSIONS: Human trabecular meshwork cells express phosphodiesterase 4, 5, and 7 gene family isoforms and enzyme activities, suggesting that selective isoform inhibitors could be used to augment the actions of antiglaucoma drugs that use cyclic nucleotides as second messengers.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2000

[Ultrastructural characteristics of glaucomatous trabecular meshwork].

PURPOSE: To compare the normal and glaucomatous trabecular meshwork ultrastructure and to relate the observed changes with the intraocular pressure increase characteristic of the primary open angle glaucoma. METHODS: 21 non glaucomatous trabecular meshworks, aged 23 to 99 years, and 5 from patients diagnosed of primary open angle glaucoma, aged 40 to 65 years, were fixed by Karnovsky's solution and processed and observed by transmission electron microscopy and their morphological characteristics were qualitatively compared. RESULTS: Ultrastructural changes of glaucomatous trabecular meshworks are similar, but much more intense, than those observed in the aged normal trabecular meshworks. These changes are loss of endothelial cells, thickening of basal membranes and trabecular beam central nucleus changes such as an increase of electrodense plaques and collagen degenerative processes. CONCLUSIONS: Ultrastructural changes observed in glaucomatous trabecular meshworks are comparable to an early aging of them. These changes can be related with the mechanisms that increase the intraocular pressure in primary open-angle glaucoma.

Adult↗
PubMed2001

The trabecular meshwork in acute and chronic angle closure glaucoma.

PURPOSE: To determine the effect of acute and chronic primary angle closure glaucoma (PACG) on the trabecular meshwork. METHODS: Trabecular specimens of 16 consecutive patients with primary angle closure glaucoma (PACG)--6 acute PACG eyes, and 10 chronic PACG eyes without an acute attack--were studied by light and electron microscopy. RESULTS: Acute PACG: The trabecular meshwork revealed a generalised oedema and an accumulation of pigment in the widened trabecular spaces and Schlemm's canal. Attenuated trabecular endothelial cells appeared to be devoid of subcellular components. Chronic PACG: In chronic PACG eyes the trabecular architecture had lost its regular arrangement, with fewer and narrower trabecular spaces and fusion of the trabecular beams in areas. There were numerous electron-dense bodies in the trabecular tissues, both within the trabecular beams and in the extracellular spaces, which had a banded fibrillar structure. An overall loss of endothelial cells was noted; the remaining cells were crowded together and were polymorphic. Melanin pigment was present both within the stroma and in the endothelial cells. CONCLUSIONS: Pigment accumulation in the trabecular spaces and within the cells and a noninflammatory degeneration appeared to be the primary changes in the trabecular meshwork after acute angle closure glaucoma. In chronic PACG eyes, there was evidence of loss of endothelial cells and reactive repair processes. These changes were present in areas away from visible peripheral anterior synechiae. A gonioscopic evaluation of the extent of peripheral anterior synechiae alone may not reflect the extent of trabecular meshwork damage in acute and chronic PACG. Patients experiencing an acute attack of PACG require a long-term follow up, because the intraocular pressure (IOP) may rise later, due to ongoing changes compromising the outflow facility, or due to the effects of aging in the trabecular meshwork.

Acute Disease↗
PubMedDate not supplied

The extracellular matrix and its modulation in the trabecular meshwork.

The extracellular matrix (ECM) in the trabecular meshwork is is believed to be essential for maintenance of the normal outflow system. Excessive, abnormal accumulations of ECM materials have been noted in the trabecular meshwork of eyes obtained from patients with primary open angle glaucoma. This review summarizes the current knowledge regarding the composition of this matrix and the receptors for ECM proteins in the trabecular meshwork. Modulations of the ECM elements by constituents in the aqueous humor after phagocytic challenges and by glucocorticoids are also described. The ECM is known to regulate cell differentiation and cell behavior in a number of systems. It will thus be of particular interest to establish the relationship between the modulated ECM and the functional status of trabecular meshwork cells and to examine the possible relevance of such modulation to outflow resistance.

Animals↗
PubMed2002

Expression profile and genome location of cDNA clones from an infant human trabecular meshwork cell library.

PURPOSE: To delineate the profile of genes expressed in infant human trabecular meshwork and identify candidate genes for glaucoma. METHODS: Human trabecular meshwork cell cultures were established from six young donors. A cDNA library was made from the combined trabecular meshwork mRNA. The end-sequence of random clones was determined by direct sequencing. These sequences were then analyzed by a National Center for Biotechnology Information (NCBI, Bethesda, MD) database search. Nucleotide searches were performed using the BLASTN (ver. 2.1.3; against the nonredundant nucleic acid sequence) and dbEST databases (both provided by NCBI in the public domain at www.ncbi.nlm.nih.gov). RESULTS: Sequences from 1118 clones from this nonamplified trabecular meshwork cDNA library were categorized. Of these, 877 expressed sequence tags (ESTs) (78.7%) were known genes. One hundred thirty-nine ESTs (12.5%) showed close identity to EST sequences reported in the public domain database (dbEST). Thirteen ESTs (1.2%) showed no significant similarity to known genes or ESTs in the public databases and were thus defined as novel ESTs. The most abundant genes expressed by the human trabecular meshwork included ferritin H, eukaryotic translation elongation factor 1-alpha, ferritin L, fibronectin, and TIMP-1. Ferritin H was the most abundant transcript, making up more than 4% of the genes expressed by the human trabecular meshwork. Extracellular matrix proteins were also highly expressed. The chromosome location of the trabecular meshwork ESTs is reported. CONCLUSIONS: A profile of genes expressed by human trabecular meshwork is presented. Thirteen novel ESTs were identified. The combined information obtained from expression analysis and chromosomal localization of trabecular meshwork cDNAs should be valuable in identifying candidate genes for glaucoma.

Cells, Cultured↗
PubMed2000

The regulation of trabecular meshwork and ciliary muscle contractility.

Current models of aqueous humor outflow no longer treat trabecular meshwork (TM) as an inert tissue passively distended by the ciliary muscle (CM). Instead, ample evidence supports the theory that trabecular meshwork possess smooth muscle-like properties and is actively involved in the regulation of aqueous humor outflow and intraocular pressure. In this model, trabecular meshwork and ciliary muscle appear as functional antagonists, with ciliary muscle contraction leading to a distension of trabecular meshwork with subsequent reduction in outflow. and with trabecular meshwork contraction leading to the opposite effect. Smooth-muscle relaxing substances would therefore appear to be ideal candidates for glaucoma therapy with the dual goal of reducing intraocular pressure via the trabecular meshwork and of improving vascular perfusion of the optic nerve head. However, for such substances to effectively lower intraocular pressure, the effect on the ciliary muscle would have to he minimal. For this reason, more information is needed on the signalling processes involved in regulating trabecular meshwork and ciliary muscle contractility. This review attempts to outline current knowledge of signal transduction pathways leading to relaxation and contraction of ciliary muscle and trabecular meshwork. Pathways can be classified as involving or not involving changes of membrane voltage and of requiring or not requiring external calcium: possibly, other pathways exist. These different pathways involve different ion channels and isoforms of PKC and are expressed to a differing degree in ciliary muscle and trabecular meshwork, leading to differential responses when exposed to relaxing or contracting pharmacological agents. Some of these agents. like tyrosine kinase inhibitors and inhibitors of PKC. have been shown to relax trabecular meshwork while leaving ciliary muscle comparatively unaffected. This profile makes these substances appear as ideal drugs for simultaneously improving ocular outflow and retinal circulation, parameters that determine the time course of visual deterioration in glaucoma.

Animals↗
PubMed2000

[Morphological alterations of the trabecular meshwork in primary open angle glaucoma].

PURPOSE: In the present essay we have compared the morphology and structure of normal trabecular meshworks and glaucomatous trabecular meshworks with the purpose of obtaining information about the etiopathogeny of primary open angle glaucoma. METHODS: We have observed by conventional light microscopy and scanning electron microscopy a total amount of 20 trabecular meshworks from non-glaucomatous patients and 35 trabecular meshworks from surgical pieces of trabeculectomy performed in patients diagnosed of primary open angle glaucoma. RESULTS: We have observed that glaucomatous trabecular meshworks show morphological and structural alterations of their trabecular beams, as their enlarging, collapse, the partial loss of endothelial cells and the existence of plenty of material accumulated on them, like pigment granules and calcium precipitates. CONCLUSIONS: Glaucomatous trabecular meshworks present morphological and structural alterations which can be related to etiopathogeny of primary open angle glaucoma since they modify the normal conditions of drainage of aqueous humour to Schlemm's channel.

Adult↗
PubMed1995

Loss of cell-matrix cohesiveness after phagocytosis by trabecular meshwork cells.

PURPOSE: To investigate the response of trabecular meshwork cells to phagocytic events. METHODS: Cultured bovine trabecular meshwork cells were established and exposed to latex microspheres for 40 to 44 hours. After phagocytosis, the cohesiveness of cells to their underlying matrix was measured by the susceptibility to trypsin, as indicated by the time needed to be liberated from culture plates. The amounts of two cell attachment proteins, fibronectin and laminin, in both the phagocytically challenged and the control cultures were measured at various postphagocytosis time points with an enzyme-linked immunosorbent assay. The fibronectin and laminin network was visualized with immunostaining. The mRNA levels were analyzed by Northern blot. Zymography using gelatin-containing gels was also performed to examine the gelatinase activities. RESULTS: Compared with controls, cells in phagocytically challenged cultures were more sensitive to trypsin. At the 4- and 8-hour postphagocytosis time points, the trypsinization time needed to suspend cells from tissue culture plates was significantly shorter for phagocytically challenged cells. Also, at these two time points, reduced amounts of fibronectin and laminin, as well as disruption of the fibronectin-laminin network, were observed in the phagocytically challenged trabecular meshwork cultures. The mRNA level for fibronectin was reduced, and a slightly increased gelatinase activity was noted. The fibronectin and laminin levels returned to normal by 24 hours. CONCLUSIONS: Results suggest that after phagocytosis, trabecular meshwork cells exhibit a short-term loss in cell-matrix cohesiveness. Such a loss may be related to diminished levels of cell attachment proteins.

Animals↗
PubMed1998

Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells.

Expression of the trabecular meshwork inducible glucocorticoid response (TIGR) gene progressively increases from barely detectable levels to greater than 2% of total cellular mRNA over 10 days exposure of trabecular meshwork (TM) cells to dexamethasone. Cycloheximide blocked most of the TIGR mRNA induction, suggesting a requirement for ongoing protein synthesis. The genomic structure of TIGR (approximately 20 kilobases) consists of 3 exons, and a 5-kilobase promoter region that contains 13 predicted hormone response elements, including several glucocorticoid regulatory elements, and other potentially important regulatory motifs. TIGR cDNA encodes an olfactomedin-related glycoprotein of 504 amino acids with motifs for N- and O-linked glycosylation, glycosaminoglycan initiation, hyaluronic acid binding, and leucine zippers. Recombinant TIGR (rTIGR) showed oligomerization and specific binding to TM cells. Anti-rTIGR antibody detected multiple translational/post-translational forms of TIGR produced by the cells (including secreted 66 kDa/55 kDa glycoproteins/proteins in the media and 55 kDa cellular proteins), whereas Northern blot showed a single mRNA species. The findings suggest potential mechanisms by which TIGR could obstruct the aqueous humor fluid flow and participate in the pathogenesis of glaucoma.

Amino Acid Sequence↗