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Nonrandom distribution of coated pits and vesicles in the connective tissue cells of the trabecular meshwork of rabbit.

Coated pits (CPs) and coated vesicles (CVs) are distributed nonrandomly along the surface of the connective tissue cells of the rabbit trabecular meshwork. Morphometric and statistical analyses of the distances between consecutive structures reveal a tendency to cluster, which is apparently higher among CVs than among CPs. The spatial relationship between CVs and CPs is also demonstrated by the analysis of their association (presence/absence) in each cell. The data suggest the hypothesis that each cluster is formed by structures in the same stage of maturation. In addition to the recent demonstration of the clustering of CPs in transformed cells in vitro (Pfeiffer et al. 1980), our findings indicate that: (a) clustering is characteristic of both CVs and CPs; (b) it also occurs in normal tissue cells; (c) it represents a further peculiarity, which confirms the specific nature of receptor-mediated endocytosis; (d) it reflects, at a higher level, the clustering of the receptor molecules, which are responsible for the high selectivity of the endocytic process.

Animals↗

Existence of heme oxygenase-carbon monoxide-cyclic guanosine monophosphate pathway in human trabecular meshwork cells in vitro.

To confirm the existence of heme oxygenase (HO)- carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HT-MCs) in vitro, and to evaluate the inductive role of hemin on this pathway, HTMCs of the third to fourth generation were cultured in vitro. Reverse transcripase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry. Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA, HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma.

Carbon Monoxide↗

Interactions between endothelia of the trabecular meshwork and of Schlemm's canal: a new insight into the regulation of aqueous outflow in the eye.

PURPOSE: To test the hypothesis that trabecular meshwork endothelial cells (TMEs) regulate aqueous outflow by actively releasing ligands that upon binding to Schlemm's canal endothelial cells (SCEs) increase transendothelial flow, thereby facilitating the egress of aqueous. METHODS: We tested our hypothesis by (1) activating the TMEs in vitro using a laser procedure known to increase aqueous outflow in vivo; (2) demonstrating that lasered TMEs become activated at the genome-wide level and synthesize ligands; (3) ascertaining that media conditioned by laser-activated TMEs and ligands therein increase transendothelial flow when added to SCEs; and (4) determining that ligands identified as synthesized by TMEs increase permeability when added to SCEs. RESULTS: We find that adding either media conditioned by lasered TMEs or ligands synthesized by TMEs to naïve control SCEs increases permeability. Adding media boiled, diluted, or conditioned by nonlasered TMEs abrogates these permeability effects. Media conditioned by either lasered TMEs or SCEs (TME-cm/SCE-cm), when added to untreated controls of each cell type, induce congruous gene expression and flow effects: TME-cm induces far more differentially expressed genes (829 in control TMEs and 1,120 in control SCEs) than does the SCE-cm (12 in control TMEs and 328 in control SCEs), and TME-cm also increases flow much more (more than 11-fold in control TMEs and more than fourfold in control SCEs) than does the SCE-cm (fivefold in control TMEs and twofold in control SCEs). CONCLUSIONS: As postulated, the TMEs release factors that regulate SCE permeability. Derangement of this TME-driven process may play an important role in the pathogenesis of glaucoma. Ligands identified, which regulate permeability, have potential use for glaucoma therapy.

Aqueous Humor↗

Analysis of porcine optineurin and myocilin expression in trabecular meshwork cells and astrocytes from optic nerve head.

PURPOSE: To determine the cDNA sequences and analyze the expression of porcine optineurin and myocilin in trabecular meshwork cells (TMCs) and astrocytes from the optic nerve head under normal and experimental conditions. METHODS: Both porcine optineurin and myocilin were cloned to determine the cDNA sequences. Porcine TMCs and astrocytes were isolated and treated with dexamethasone (500 nM) for 2 weeks, incubated under hypoxic conditions (7% O(2)) for 72 hours, or exposed to 33 mm Hg hydrostatic pressure for 72 hours. A 10% mechanical stretch for 24 hours was also performed on TMCs. The expression level of the optineurin and myocilin transcripts was analyzed by real-time quantitative PCR. RESULTS: The sequences of porcine optineurin and myocilin cDNA were determined, and the expression of both genes was confirmed in both TMCs and astrocytes. Amino acid sequences of porcine optineurin and myocilin were homologous to those of humans by 84% and 82%, respectively, and shared protein motifs and modification sites. The expression of myocilin mRNA by TMCs and astrocytes was increased by 8.0- and 5.5-fold, respectively, after exposure to dexamethasone. In contrast, the expression of optineurin was suppressed to 68% in TMCs and 48% in astrocytes after exposure to dexamethasone. A significant reduction of myocilin expression was observed after 72 hours of incubation under hypoxic conditions in both types of cells, whereas optineurin was not affected. Hydrostatic pressure for 72 hours and mechanical stretching for 24 hours had minimal affects on gene expression of both optineurin and myocilin. CONCLUSIONS: The high homology of porcine optineurin and myocilin to the comparable human genes indicates that pigs can be used to study changes in gene expression in hypertensive eyes. The alterations in expression of myocilin but not of optineurin under stress suggest that different mechanisms in the phenotype of glaucoma associated with the two genes are involved in development of glaucoma.

Amino Acid Sequence↗

Differential expression of the human chloride channel genes in the trabecular meshwork under stress conditions.

Among other channels, voltage-gated chloride channels (ClC) regulate cell volume, membrane potential and cellular transport. Because changes in trabecular meshwork (TM) cell volume influence outflow facility and because the relative abundance of a gene's transcript is an indication of the relevance of the gene's function, we investigated the presence and relative expression of seven members of the CLCN gene family in the human TM. To elucidate the role of ClC-2 and ClC-3 in cell swelling, we studied changes in their mRNA levels after hypotonic shock. In addition, to examine the potential involvement of these two channels in conditions associated with glaucoma, we determined their transcripts levels in response to elevated intraocular pressure (IOP) and dexamethasone (DEX). For our evaluations, we used non-transformed human TM cells and perfused human anterior segments from post-mortem donors. For hypotonic shock, cells were exposed to 260 mOsm kg(-1) medium for 15 and 30 min. For DEX, cells were treated with 0.1 microm DEX for 1, 4 and 10 days. For elevated IOP, one eye of each pair of perfused human anterior segments was subjected to DeltaP 38+/-4 mm Hg for 1 hr, 4 and 7 days while the contralateral remained at baseline pressure as a control. ClCs transcripts were determined by relative quantitative RT-PCR. Our results showed that all transcripts but ClC-1 were detected in HTM cells. ClC-2 and ClC-3 were the most abundant and comprised about twice the amount of ClC-6 and ClC-7 and four times that of ClC-4 and ClC-5. Hypotonic conditions consistently up regulated CLCN2 and slightly up regulated CLCN3. After short periods of elevated pressure, ClC-2 and ClC-3 transcripts were increased but ClC-2 induction was significantly higher than that of ClC-3. In contrast, after long pressure insults (7 days), ClC-3 mRNA was significantly increased while CLCN2 was not changed. DEX treatment markedly down regulated CLCN3 and little, if any, reduced ClC-2. The extent of response of the CLCN2 and CLCN3 to these conditions was markedly affected by individual traits but at all times maintained the relative expression pattern of both genes. CLCN2 gene expression was predominantly influenced by cell volume regulation while that of CLCN3 was preferentially affected by conditions associated with TM pathology.

CLC-2 Chloride Channels↗

[Laser treatment for tightening the trabecular meshwork in open-angle glaucoma (trabeculoplasty)].

Forty eyes with medically uncontrolled open-angle glaucoma underwent argon laser therapy through 360 degrees of the trabecular meshwork. The mean pressure change in the treated eyes after two weeks showed a decrease of 9.95 mmHg. Thirty-five eyes (87.5%) were clinically controlled (tension less than or equal to 20 mmHg) either by laser treatment alone (25 eyes) or by continuation of previous therapy (10 eyes) over the various follow-up periods ranging from one to ten months (means = 3.31). Laser therapy showed no hypotensive reaction in five eyes. Increased pressure immediately after therapy seems to be the most severe side effect, which was of short duration in all cases but two.

Glaucoma, Open-Angle↗

Pharmacological and functional characterization of endothelin receptors in bovine trabecular meshwork and ciliary muscle.

To clarify the potential role of endothelin-1 (ET-1) in the pathogenesis of glaucoma, the endothelin receptors expressed in bovine trabecular meshwork (TM) and ciliary muscle (CM) were identified. TM and CM strips were subjected to ET-1 as well as to specific endothelin receptor antagonists. In both tissues BQ123, a specific ET-A receptor antagonist, substantially inhibited ET-1-induced contraction. BQ788, a specific ET-B receptor antagonist, showed only moderate effects. Both ET receptor types were detected in bovine TM and CM using Western blot analysis. ET-1 produced an increase in intracellular calcium in cultured TM cells. This effect was inhibited by BQ123, but not by BQ788. Thus, although both receptors are present, the ET-A receptor appears to play the predominant role in mediating contraction in both the TM and CM, while the ET-B receptor seems to contribute little to the overall ET-1 effect.

Animals↗

[Biochemical analysis of proteoglycan in bovine trabecular meshwork and its significance].

OBJECTIVE: To determine the kinds of proteoglycan (PG) monochain and their distribution in the cell layer and cultural medium of bovine trabecular meshwork (BTM) culture. METHODS: (3)H-glycosamine was incorporated in BTM cells in the third passage. PGs were extracted by 4 mol/L guanidine hydrochloride. The aliquots were chromatographed on Sephadex G-50 DEAE-Sephacel, Sepharose 4B and Sepharose CL-6B gel respectively. Glycosaminoglycan was obtained by basic hydrolysis and enzyme degradation, and scintillation counting was used for the assay of radioactivity. RESULTS: Four different PGs were analyzed. The composition of PGs in cell layer was hyaluronic acid PG 30.2%, heparin sulfate PG 20.9%, chondroitin sulfate PG 21.6%, dermatan sulfate PG 18.1% and others 9.2%, while in the medium was 24.2%, 20.1%, 25.7%, 23% and 7%, respectively. CONCLUSIONS: PGs are confirmed to be present in the extracellular matrix of BTM cells in vitro. BTM cells also have the ability to secrete these macromolecules into the medium. Abnormal synthesis, secretion, accumulation and changes of PG pattern in physiologic conditions and under any drugs may contribute to the pathogenesis and treatment of primary open-angle glaucoma.

Animals↗

[The effect of endothelial leukocyte-adhesion molecule-1 on the shape and cytoskeleton of porcine trabecular meshwork cells].

OBJECTIVE: To study the effects of endothelial leukocyte-adhesion molecule-1 (ELAM-1) on the shape and actin cytoskeleton of cultured porcine trabecular meshwork cells (PTCs). METHODS: The cultured PTCs were stimulated by interleukin-1 (IL-1) and conjugated by ELAM-1 antibody or further cross-linked by IgG. Immunocytochemical procedures were used to study the expression of ELAM-1 and FITC-phalloidin was used to stain the actin filaments on PTCs; phase contrast microscope was employed to observe the dynamic changes of cellular shape and the intercellular conjunction and confocal microscope was used to observe the changes of actin and cellular thickness. RESULTS: IL-1 treatment increased the expression of ELAM-1 in PTCs which resulted in enlarged intercellular space in PTCs with more rounded and stereoscopic morphology after specific antibody conjugation or IgG cross linking. In addition, actin filaments became sparse, cellular rigidity decreased, and the cellular thickness increased after these treatments. CONCLUSIONS: Our results demonstrated that IL-1 activated PTCs can express ELAM-1 and interaction of ELAM-1 with specific antibodies and cross linking with IgG, induced a rounding-up of PTCs. This change in cell shape may be due to its action on the actin cytoskeleton.

Actins↗

Endothelia of Schlemm's canal and trabecular meshwork: distinct molecular, functional, and anatomic features.

The purpose of this study was to compare human endothelial cells from Schlemm's canal (SCEs) and the trabecular meshwork (TMEs) in terms of ZO-1 isoform expression, hydraulic conductivity (HC) properties, and "giant" vacuole (GV) formation. The principal study methods were Western blot, RT-PCR, immunofluorescence, and perfusion chambers. Blot signals for alpha+ - and alpha- -isoforms were similar in SCEs but less intense for the alpha+ -relative to the alpha- -signal in TMEs. With the anti-alpha+ antibody used at 1/50 dilution, binding occurred at cell borders of both cell types, but only to SCEs when used at a >/=1/200 dilution in vitro and in vivo. SCEs were more resistive than TMEs (HC = 0.66 vs. 1.32 microl.min-1.mmHg-1.cm-2; P < 0.001) when perfused from apex to base. When perfused in the other direction, SCEs were again more resistive (5.23 vs. 9.04 microl.min-1.mmHg-1.cm-2; P < 0.01). GV formation occurred only in SCEs as a function of flow direction, perfusion pressure, and time. We conclude that SCEs and TMEs have distinctive phenotypic properties involving their content of ZO-1 isoforms, barrier function, and GV formation.

Actins↗

Rho-associated protein kinase inhibitor, Y-27632, induces alterations in adhesion, contraction and motility in cultured human trabecular meshwork cells.

We investigated the roles of Rho-associated protein kinase (ROCK) in regulating activities such as adhesion, contraction and migration in cultured human trabecular meshwork (TM) cells. Human TM cells in culture were treated with Y-27632, a specific ROCK inhibitor. Trypan blue exclusion test and TUNEL staining showed little or no direct toxicity of Y-27632 on TM cells. By MTT assay, Y-27632 did not significantly affect the proliferation of TM cells. The cell adhesion assay showed that Y-27632 promoted the cell adhesiveness to both fibronectin and collagen type I in a dose-dependent manner. Collagen gel contraction activity of TM cells was significantly inhibited by the treatment of Y-27632 in a dose-dependent manner. The addition of Y-27632 accelerated motility of TM cells in wound healing assay. Phosphorylated LIM kinase 2 and cofilin, related to actin bundling and integrin clustering, were dephosphorylated (activated) by Y-27632. In conclusion, Y-27632 elicits profound effects on TM cell activities including adhesion, gel contraction, and cell motility. These Y-27632-induced changes of TM cells may be relevance to the physiology of the aqueous outflow system.

Amides↗

Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells.

PURPOSE: To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the trabecular meshwork (TM). METHODS: Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS: The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 (in four of five cultures), MMP-3 (in four of five cultures), MMP-17 (in three of five cultures), MMP-24 (in all five cultures), TIMP-2, -3, and -4 expression (in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS: Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow.

Adult↗

Efferent and afferent innervation of primate trabecular meshwork and scleral spur.

PURPOSE: To determine the correlation between nerve terminals and cells or extracellular matrix (ECM) components in different portions of the primate trabecular meshwork (TM) and scleral spur (SS). METHODS: Serial sagittal and tangential sections through the anterior segments of 10 cynomolgus monkey eyes and 12 human eyes were investigated immunohistochemically with antibodies against the vesicular acetylcholine transporter (VACHT), vasoactive intestinal polypeptide (VIP), tyrosine-hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), and galanin (GAL) and with a reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) reaction. The distribution of the terminals was compared with that of alpha-smooth-muscle actin (SMA) staining in TM and SS. The relationship between terminals and adjacent cells or ECM components was also studied in ultrathin sections through the TM and SS of 11 monkey eyes cut in sagittal, tangential, and frontal planes. RESULTS: NADPHd-positive nerve terminals were present, especially in the outer portion of both human and monkey TM and in the SS. VACHT-immunoreactive (IR) fibers were found in human but not in monkey SS and TM. The fibers were most numerous in the elongated SS and posterior TM where most cells also stained for SMA. SP- and CGRP-IR nerve endings were also more numerous in the outer TM and SS than in the inner TM. Ultrastructurally, staining for SP was seen in nerve endings containing mitochondria and dense core vesicles and was in contact with the cribriform elastic network. In the posterior SS of monkey eyes were large terminals similar to those previously described in human eyes. CONCLUSIONS: The results show for the first time that in the primate TM and SS, there are cholinergic and nitrergic nerve terminals that could induce contraction and relaxation of TM and SS cells. Terminals in contact with the elastic-like network of the TM and containing SP-IR resemble afferent mechanoreceptor-like terminals in other parts of the body. These findings raise the possibility that the TM may have some ability to self-regulate aqueous humor outflow.

Actins↗

Primary lasertrabeculoplasty a comparison of 50 spots in 180 degrees and 100 spots in 360 degrees of the trabecular meshwork.

Primary LTP was performed in 20 eyes with 50 spots in 180 degrees and in 26 eyes with 100 spots in 360 degrees of the trabecular meshwork. These eyes had received no earlier glaucoma medication. They were followed prospectively for 12 months. Prelaser IOP was 36.3 +/- 8.0 mmHg in the 50 spot group and 35.9 +/- 6.6 mmHg in the 100 spot group. Treatment was considered successful if IOP was less than or equal to 22 mmHg with no medication and no further disk damage or loss of visual field. The success rate 12 months after LTP was 15% in the 50 spot group and 69% in the 100 spot group.

Aged↗

Human trabecular meshwork cells in culture: morphology and extracellular matrix components.

This study demonstrates the presence of laminin and collagen type IV in the extracellular space of human trabecular meshwork (HTM) cells in culture and its absence in cultures of fibroblasts from sclera adjacent to the outflow pathway. These basement membrane components can be detected by standard immunohistochemical techniques. Positive staining for these macromolecules is found only after the HTM cells have reached confluence. The presence of laminin and human collagen type IV in the early passages can serve as additional criteria for identification of HTM cells in culture. These cells provide a useful experimental system for studying the effects of drugs and other factors on the synthesis of components of the extracellular matrix.

Adolescent↗

The presence of macrophage migration inhibitory factor in human trabecular meshwork and its upregulatory effects on the T helper 1 cytokine.

PURPOSE: To investigate the expression and secretion of macrophage migration inhibitory factor (MIF) in human trabecular meshwork (HTM) and evaluate its role in ocular inflammation. METHODS: Tissue samples of HTM cells were isolated from donor human eyes or corneoscleral buttons, and the HTM cells were cultured. The expression of MIF on HTM cells was evaluated by RT-PCR, Western blot analysis, and ELISA. T-cell clones (TCCs) were established from ocular infiltrating cells of patients with uveitis. ELISA was used to evaluate the pathologic role of MIF, in relation to regulatory effects on cytokine production by T cells. RESULTS: MIF was detected in the HTM by RT-PCR and Western blot analysis. MIF was also shown by ELISA to be secreted by the HTM cells in culture. The HTM supernatant enhanced IFN-gamma production by TCCs, but not IL-10; and these effects were neutralized by anti-MIF antibodies. Similarly, recombinant MIF enhanced the IFN-gamma production by the TCCs. CONCLUSIONS: MIF is expressed and secreted in the HTM, and MIF has the capacity to enhance T helper 1 cytokines and may play a role as an inflammatory cytokine in the eye.

Adolescent↗

Beta1 and beta3 integrins cooperate to induce syndecan-4-containing cross-linked actin networks in human trabecular meshwork cells.

PURPOSE: To characterize the molecular composition of cross-linked actin networks (CLANs) and the regulation of their formation by integrins in normal human trabecular meshwork (TM) cells. CLANs have been observed in steroid-treated and glaucomatous TM cells and have been suggested to contribute to decreased outflow facility by altering the contractility of the TM. METHODS: Immunofluorescence microscopy was used to identify molecular components of CLANs and quantitate CLAN formation in HTM cells plated on coverslips coated with various extracellular matrix (ECM) proteins (fibronectin, types I and IV collagen, and vitronectin), vascular cell adhesion molecule (VCAM)-1, or activating antibodies against beta1, beta3, or alpha2beta1 integrins. These integrin antibodies were also used as soluble ligands. RESULTS: CLAN vertices contained the actin-binding proteins alpha-actinin and filamin and the signaling molecules syndecan-4 and PIP2. CLANs lacked Arp3 and cortactin. CLAN formation was dependent on the ECM substrate and was significantly higher on fibronectin and VCAM-1 compared with vitronectin, types I or IV collagen. Adsorbed beta1 integrin antibodies also induced CLANs, whereas adsorbed beta3 or alpha2beta1 integrin antibodies did not. Soluble beta3 integrin antibodies, however, induced CLANs and actually enhanced CLAN formation in cells spread on fibronectin, VCAM-1, type I or type IV collagen, or beta1 integrin antibodies. CONCLUSIONS: CLANs are unique actin-branched networks whose formation can be regulated by beta1 and beta3 integrin signaling pathways. Thus, integrin-mediated signaling events can modulate the organization of the actin cytoskeleton in TM cells and hence could participate in regulating cytoskeletal events previously demonstrated to be involved in controlling outflow facility.

Actin Cytoskeleton↗

Aqueous humor dynamics and trabecular meshwork and anterior ciliary muscle morphologic changes with age in rhesus monkeys.

PURPOSE: To determine in rhesus monkeys the age-dependence of uveoscleral outflow (Fu) and morphology of the trabecular meshwork (TM) and anterior ciliary muscle (CM). METHODS: Intraocular pressure (IOP) was measured by Goldmann applanation tonometry in monkeys under ketamine anesthesia. After anterior chamber cannulation under pentobarbital anesthesia, aqueous humor formation (AHF), anterior chamber volume, trabecular outflow, and Fu were determined isotopically. The CM and TM were examined by light and electron microscopy. RESULTS: IOP increased significantly with age in monkeys aged 3 to 29 years. AHF and anterior chamber volume were unchanged. Fu was decreased, and trabecular outflow increased in monkeys aged 25 to 29 years compared with the remaining monkeys. Morphologically, there was a significant increase in the thickness of the elastic fibers of the trabeculum ciliare covering the anterior tips of the CM, and an increase in extracellular material between the muscle tips. The number of TM cells decreased with age, whereas the amount of fibrillar material and sheath-derived plaques increased. This increase was less pronounced in the middle filtering portion of the cribriform region than in the anterior and posterior portions. CONCLUSIONS: The decline in Fu in very old rhesus monkeys with normal IOP parallels that seen in normotensive aging humans. This may be correlated with thickening of the elastic fiber sheath in the CM tips in addition to other morphologic changes. The TM findings are analogous to those in the aging human eye and are consistent with the age-related decrease in outflow facility reported in both humans and monkeys.

Aging↗