Wall Of Schlemm Research Articles

Digital spatial profiling of segmental outflow regions in trabecular meshwork reveals a role for ADAM15.

In this study we used a spatial transcriptomics approach to identify genes specifically associated with either high or low outflow regions in the trabecular meshwork (TM) that could potentially affect aqueous humor outflow in vivo. High and low outflow regions were identified and isolated from organ cultured human anterior segments perfused with fluorescently-labeled 200 nm FluoSpheres. The NanoString GeoMx Digital Spatial Profiler (DSP) platform was then used to identified genes in the paraffin embedded tissue sections from within those regions. These transcriptome analyses revealed that 16 genes were statistically upregulated in high outflow regions and 57 genes were statistically downregulated in high outflow regions when compared to low outflow regions. Gene ontology enrichment analysis indicated that the top three biological categories of these differentially expressed genes were ECM/cell adhesion, signal transduction, and transcription. The ECM/cell adhesion genes that showed the largest differential expression (Log2FC ±1.5) were ADAM15, BGN, LDB3, and CRKL. ADAM15, which is a metalloproteinase that can bind integrins, was upregulated in high outflow regions, while the proteoglycan BGN and two genes associated with integrin signaling (LDB3, and CRKL) were downregulated. Immunolabeling studies supported the differential expression of ADAM15 and showed that it was specifically upregulated in high outflow regions along the inner wall of Schlemm's canal and in the juxtacanalicular (JCT) region of the TM. In addition to these genes, the studies showed that genes for decorin, a small leucine-rich proteoglycan, and the α8 integrin subunit were enriched in high outflow regions. These studies identify several novel genes that could be involved in segmental outflow, thus demonstrating that digital spatial profiling could be a useful approach for understanding segmental flow through the TM. Furthermore, this study suggests that changes in the expression of genes involved in regulating the activity and/or organization of the ECM and integrins in the TM are likely to be key players in segmental outflow.

Decreased outflow facility and Schlemm's canal defects in a mouse model of glaucoma.

Previously we identified B6.EDA+/+ mice as a novel mouse model that presents with elevated IOP and trabecular meshwork damage. Here, we expand on our previous findings by measuring aqueous humor outflow facility and analyzing the integrity of the inner wall of Schlemm's canal. As expected, intraocular pressure (IOP) was increased, and outflow facility was decreased compared to C57BL/6J controls. B6.EDA+/+ mice had significantly increased expression of the adherens junction protein, VE-cadherin by the inner wall endothelium of Schlemm's canal. These data suggest that in addition to trabecular meshwork damage, there are changes in Schlemm's canal in B6.EDA+/+ mice that lead to aqueous outflow dysfunction and ocular hypertension.

Topographic distribution and phenotypic heterogeneity of Schlemm's canal endothelium in human donor eyes

Endothelium phenotype is known to be closely associated with flow shear stress. This study is to determine the topographic distribution of endothelial cells and the phenotype of different quadrants and regions of Schlemm's canal using human donor eyes. This study infers differences in flow dynamics based on cell shape and intracellular structure. The Schlemm's canal from 15 human donor eyes were either perfusion labelled using silver stain or dissected for float labeling with Phalloidin to enable visualization of endothelial cell border and intracellular structure. Data were acquired for endothelial cells from the outer and inner wall of Schlemm's canal and grouped according to quadrant of origin. Measurements included endothelial cell length, width, area, and aspect ratio and compared between quadrants. Endothelial cells are mostly spindle-shape and the cell size on the outer wall are larger and longer than those from the inner wall. Significant differences in endothelial cell size and shape were seen in different quadrants. The endothelial cells have varied shapes and orientations close to large ostia in the outer wall and remarkably long endothelial cells were found in the walls of collector channels. F-actin aggregation was found at all endothelial cell borders, and inside some of the endothelial cytoplasm. The presence of various spindle shapes, significant phenotype heterogeneity and F-actin aggregation of endothelial cells indicates aqueous humor flow likely creates variations in shear stress within Schlemm's canal. Further investigation of the relationship between the phenotype heterogeneity and hydrodynamics of aqueous flow may help us understand the mechanisms of outflow resistance changes in glaucoma.

Combined Circumferential Canaloplasty and Trabeculotomy Ab Interno with the OMNI Surgical System

In the normal eye the conventional outflow pathway is responsible for the majority of aqueous humor egress and plays a key role in the maintenance of healthy intraocular pressure. However, in the glaucomatous eye pathologic changes to the pathway in the trabecular meshwork, Schlemm’s canal, and collector channel ostia can introduce abnormal resistance to outflow with consequent increase in intraocular pressure. The OMNI Surgical System (Sight Sciences, Menlo Park, CA USA) is a relatively new surgical device and the only one that combines two ab interno minimally invasive treatments in a single procedure, canaloplasty and trabeculotomy. This new technology allows surgeons to address outflow resistance wherever it may be, both proximally (juxtacanalicular trabecular meshwork and inner wall of Schlemm’s canal), and distally (Schlemm’s canal and the collector channels). This review covers several recent clinical studies of the OMNI device with the aim of collating what is known and what remains to be learned.

Observation of Gonio Structures during Microhook Ab Interno Trabeculotomy Using a Novel Digital Microscope with Integrated Intraoperative Optical Coherence Tomography.

Purpose Observation of ocular structures using microscope-integrated intraoperative optical coherence tomography (iOCT) has been adopted. Using the novel digital ophthalmic microscope, ARTEVO 800 with iOCT, we tested the feasibility of trabecular meshwork (TM) imaging during microhook ab interno trabeculotomy, a minimally invasive glaucoma surgery. Methods The nasal and temporal sides of the TM/inner wall of Schlemm's canal were incised more than 3 clock hours in 14 glaucomatous eyes of 10 patients. To observe the trabeculotomy site, iOCT was performed with the real-time five-line scan mode under observation using a Swan-Jacob gonioprism lens. The success of the imaging and visibility of the trabeculotomy cleft and its incisional patterns (i.e., anterior, middle, or posterior pattern) were determined by reviewing the iOCT video files. Results OCT images of the region of interest were acquired successfully in 100% of the 28 nasal or temporal sides in 14 eyes, although the trabeculotomy cleft was not visualized in four (14%) sides due to blockage of the OCT signal by a blood clot. Based on the predominant locations of the TM flaps in 24 of the acquired images, the trabeculotomy clefts were classified as anterior incisional patterns in 13 (54%), middle incisional patterns in nine (38%), and posterior incisional patterns in two (8%). Conclusion Intraoperative imaging of the gonio structures including the trabeculotomy cleft was feasible using the ARTEVO 800 with iOCT in combination with a gonioprism.

Circumferential canal surgery: a brief history.

Purpose of reviewMost microinvasive glaucoma surgery (MIGS) procedures bypass outflow resistance residing proximally in the trabecular meshwork and inner wall of Schlemm's canal. A novel procedure combining trabeculotomy with viscodilation adds to this by also addressing distal resistance of the canal and collector channel ostia. This review examines the development and evidence for both trabeculotomy and canaloplasty separately and the combination in a single procedure.Recent findingsRecent aqueous angiography studies have confirmed the segmental nature of outflow through Schlemm's canal highlighting the need to address distal outflow pathway resistance. Combined trabeculotomy and viscodilation ab interno is a novel approach with a new purpose-designed device (OMNI Surgical System) becoming available to surgeons in early 2018. Recent results as both a standalone and combined with cataract procedure demonstrate significant intraocular pressure reductions with an average 41% reduction from baseline in the pseudophakic group.SummaryTargeting both distal as well as proximal points of outflow resistance in the conventional pathway may prove to be a highly efficacious MIGS modality. Additional large prospective studies are currently ongoing to confirm these preliminary results.

Increased stiffness and flow resistance of the inner wall of Schlemm’s canal in glaucomatous human eyes

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ∼1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model

Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm's canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.

SB772077B, A New Rho Kinase Inhibitor Enhances Aqueous Humour Outflow Facility in Human Eyes

We investigated the effect of a new Rho kinase inhibitor, SB772077B (SB77) on aqueous outflow facility (OF) in human eyes using human organ-cultured anterior segment (HOCAS). IOP was monitored for 24 h post-treatment with either SB77 (0.1/10/50 µM) or vehicle after a stable baseline pressure. The hydrodynamic pattern of aqueous outflow was analysed by labelling outflow pathway with red fluorescent microspheres. The effect of SB77 on cell morphology, actin stress fibers, focal adhesions, ECM, status of RhoA activation and myosin light chain phosphorylation (p-MLC) were evaluated and compared with Y27632, by immunostaining using primary human trabecular meshwork (HTM) cells. Following 24 h treatment, SB77 increased OF by 16% at 0.1 µM (N = 6), 29% at 10 µM (N = 8; p = 0.018) and 39% at 50 µM (N = 8; p = 0.004) in human eyes. There was an overall increase in tracer quantity and in area along inner wall of Schlemm’s canal. Treatment with SB77 showed no evidence of cytotoxicity and caused a significant reduction in the expression of fibrotic markers compared to Y27632. The present findings indicate that SB77 treatment was effective in enhancing OF and reducing fibrotic markers in an ex vivo model. Thus SB77 may be a potential clinical candidate for the management of glaucoma.

Microhook ab interno trabeculotomy, a novel minimally invasive glaucoma surgery.

Trabeculotomy (LOT) is performed to reduce the intraocular pressure in patients with glaucoma, both in children and adults. It relieves the resistance to aqueous flow by cleaving the trabecular meshwork and the inner walls of Schlemm’s canal. Microhook ab interno LOT (µLOT), a novel minimally invasive glaucoma surgery, incises trabecular meshwork using small hooks that are inserted through corneal side ports. An initial case series reported that both µLOT alone and combination of µLOT and cataract surgery normalize the intraocular pressure during the early postoperative period in Japanese patients with glaucoma. Microhook can incise the inner wall of Schlemm’s canal without damaging its outer wall easier than the regular straight knife that is used during goniotomy. Advantages of µLOT include: a wider extent of LOT (two-thirds of the circumference), a simpler surgical technique, being less invasiveness to the ocular surface, a shorter surgical time than traditional ab externo LOT, and no requirement for expensive devices. In this paper, the surgical technique of µLOT and tips of the technique are introduced.

Stiffness characterization of anisotropic trabecular meshwork

Elevation of intraocular pressure has been correlated to changes in stiffness of trabecular meshwork (TM) in glaucomatous eyes although mechanical properties of the TM remain to be quantitatively determined. Data in the literature suggest that the TM cannot be considered mechanically as a uniform layer of isotropic elastic material, because the value of its Young’s modulus depends on the methods of measurements and can vary up to five orders of magnitude. To this end, we proposed a new theoretical framework for mechanical analysis of the TM, in which the inner wall of Schlemm’s canal and the juxtacanalicular tissue in the TM were treated as a uniform layer of isotropic elastic material, and the rest of the TM, i.e., the uveal and corneoscleral meshworks, were modeled as a uniform layer of transversely isotropic material. Using the model, we demonstrated that the large discrepancy in the apparent Young’s modulus reported in the literature could be caused by the anisotropy of the meshwork that was significantly stiffer in the longitudinal direction than in the transverse direction. The theoretical framework could be used to integrate existing data of the stiffness, investigate anisotropic behaviors of the tissues, and develop new methods to measure mechanical properties of the TM.

Ab interno Schlemm's Canal Surgery.

In primary open-angle glaucoma, the site of greatest resistance to aqueous outflow is thought to be the trabecular meshwork (TM) and inner wall of Schlemm's canal. Augmentation of the conventional (trabecular) outflow pathway can facilitate physiologic outflow and subsequently lower intraocular pressure. The most recent approach to enhancing the conventional outflow pathway is via an internal approach to the TM and Schlemm's canal. Ab interno Schlemm's canal surgery includes 4 novel surgical approaches: (1) removal of the TM and inner wall of Schlemm's canal by an internal approach (ab interno trabeculectomy), (2) implantation of a microstent to bypass the TM, (3) disruption of the TM and inner wall of Schlemm's canal via an internal approach (ab interno trabeculotomy), and (4) dilation of Schlemm's canal via an internal approach (ab interno canaloplasty). The first category includes the Trabectome (Neomedix, Tustin, CA, USA), and Kahook Dual Blade (New World Medical, Rancho Cucamonga, CA, USA). The second category includes the iStent (Glaukos, Laguna Hills, CA, USA), as well as the investigational Hydrus Microstent implant (Ivantis, Irvine, CA, USA). The third category includes gonioscopic-assisted transluminal trabeculotomy (iSciences catheter; Ellex, Adelaide, Australia), and 360° suture trabeculotomy (TRAB360, Sight Sciences, Menlo Park, CA, USA). The fourth category includes ab interno canaloplasty or AbiC (Ellex), and Visco360 (Sight Sciences). In contrast to external filtration surgeries, such as trabeculectomy and aqueous tube shunt, these procedures are categorized as internal filtration surgeries and are performed from an internal approach via gonioscopic guidance. Published results suggest that these surgical procedures are both safe and efficacious for the treatment of open-angle glaucoma.

Deep Sclerectomy.

Filtering surgery evolved from the classic trabeculectomy, in which penetration into the anterior chamber is a necessary step, toward nonpenetrating deep sclerectomy. The first procedure presents several serious complications, such as durable hypotony, hyphema, flat anterior chamber, choroidal detachment, endophthalmitis, and surgery-induced cataract. To avoid such drawbacks, a novel nonpenetrating technique was designed to improve the predictability of the intraocular pressure (IOP)-lowering action, while reducing the incidence of the immediate postoperative complications encountered with the penetrating method. This surgery works by building up new outflow pathways for the drainage of the aqueous humor while maintaining the integrity of the anterior chamber. Deep sclerectomy acts at the bulk of main resistance to aqueous humor egress, located at the juxtacanalicular meshwork and at the inner wall of Schlemm's canal. It consists of dissection of these two structures while keeping a thin filtering membrane through which aqueous humor is drained. The membrane prevents overfiltration and ensures a reproducible postoperative IOP. This surgery is indicated for most glaucomas, with the exception of angle closure and neovascular cases. The procedure consists in opening the conjunctiva and Tenon's capsule and creating a 5 × 5-mm limbus-based superficial scleral flap. A deeper scleral flap measuring about 4 × 4 mm is dissected and the roof of Schlemm's canal is removed. A space maintainer is inserted and the flap and conjunctiva are closed. Results after 10 years are good, with an IOP of 12.2 ± 4.7 mmHg and an overall success rate of 77.6% with few complications.

Optical Coherence Tomography Observation of Gonio Structures during Microhook Ab Interno Trabeculotomy.

Introduction Intraoperative observation of ocular structures using microscope-integrated optical coherence tomography (iOCT) has been adopted recently. I report my initial feasibility assessment of iOCT for the incised trabecular meshwork observation during microhook ab interno trabeculotomy. Case Series Both the nasal and temporal sides or either side of the trabecular meshwork/inner wall of Schlemm's canal was incised more than 3 clock hours. After then, under observation using a Swan-Jacob gonioprism lens with the real-time 5-line scan mode, OCT images of the area were successfully acquired in 10 (83%) of 12 sides in nine eyes. Based on the appearance of the acquired images of the 10 sides, the trabeculotomy cleft could be classified into three incisional patterns, that is, six (60%) anterior-opening patterns (posterior-based flap), three (30%) middle-opening patterns (posterior- and anterior-based flaps), and one (10%) posterior-opening pattern (anterior-based flap), according to the predominant locations of the trabecular meshwork flaps. Conclusion Intraoperative observation of the gonio structures including the trabeculotomy cleft was feasible using the RESCAN 700 in combination with a gonioprism.

Ab interno trabeculectomy: patient selection and perspectives.

Ab interno trabeculectomy is one among several recently introduced minimally invasive glaucoma surgeries that avoid a conjunctival incision and full-thickness sclerostomy involved in traditional glaucoma surgery. Ablation of the trabecular meshwork and inner wall of Schlemm’s canal is performed in an arcuate fashion via a clear corneal incision, alone or in combination with phacoemulsification cataract surgery. Intraocular pressure reduction following ab interno trabeculectomy is limited by resistance in distal outflow pathways and generally stabilizes in the mid-to-high teens. Relief of medication burden has been demonstrated by some studies. A very low rate of complications, most commonly transient hyphema and intraocular pressure elevations in the immediate postoperative period, have been reported. However, available data are derived from small retrospective and prospective case series. Randomized, controlled trials are needed to better elucidate the potential merits of ab interno trabeculectomy in the combined setting versus phacoemulsification cataract surgery alone and to compare it with other minimally invasive glaucoma surgeries.

Expression Profiling of Human Schlemm's Canal Endothelial Cells From Eyes With and Without Glaucoma.

Ocular hypertension is a major risk factor for glaucoma and the inner wall of Schlemm's canal (SC) endothelia participates in the regulation of aqueous humor outflow resistance. This study aimed to identify differentially expressed genes in primary cultures of SC cells from glaucoma patients. This study examined SC samples from three glaucoma cases and four controls. Schlemm's canal cells were isolated from eight different postmortem human eyes. Total RNA was extracted, labeled, and hybridized to Illumina HumanWG-6 BeadChips containing probes for approximately 47,000 human transcripts. After extracting the data using Illumina GenomeStudio software, the data were normalized and analyzed using the R package limma in Bioconductor. Using Protein ANalysis THrough Evolutionary Relationships (PANTHER) software, gene ontology analysis of highly expressed genes was executed in controls and glaucoma groups separately. Pathway analysis was performed with differentially expressed genes using WebGestalt (WEB-based GEne SeT AnaLysis Toolkit). Selected genes were validated using droplet digital PCR (ddPCR). Gene ontology analysis indicated similar functional categories in cases and controls. Differential analysis identified a total of 113 genes with at least 2-fold expression changes in cases. Pathway analysis indicated significant enrichment of genes in cell adhesion, heparin binding, glycosaminoglycan binding, filopodium, and extracellular matrix remodeling. Eighteen selected genes with differential expression were successfully validated using ddPCR. This study represents the first genome-wide expression study of human primary SC cells from glaucoma patients and provides a potential list of targets regulating SC cell stiffness and pore formation, eventually the outflow resistance in glaucoma individuals.

Channelography and mechanism of action in canaloplasty

Canaloplasty lowers the intraocular pressure (IOP) by restoring the natural outflow system. The success of canaloplasty depends on the function of this system. To evaluate the natural outflow system regarding canaloplasty by two clinical tests, provocative gonioscopy and channelography and to describe the mechanism of action of canaloplasty. Provocative gonioscopy evaluates the pattern of blood reflux which is induced by ocular hypotension as the result of a reversed pressure gradient between the episcleral venous pressure and IOP following paracentesis. In channelography the transtrabecular diffusion and the filling properties of the episcleral venous system are assessed by a microcatheter and a fluorescein tracer. Blood reflux varied greatly in glaucomatous eyes and showed an inverse correlation with the preoperative IOP. The higher the IOP, the poorer the blood reflux. The filling qualities of the episcleral venous system and diffusion through the trabecular meshwork were different. Poor trabecular passage and good episcleral fluorescein outflow indicates patent distal outflow pathways, poor trabecular passage and poor episcleral fluorescein outflow indicates obstructed trabecular meshwork and closed collector channels and good trabecular passage together with poor episcleral fluorescein outflow suggests that the site of impairment is mainly in the distal outflow system. The quality of blood reflux and the characteristics of the episcleral filling and the transtrabecular diffusion by fluorescein represent the clinical state of the outflow pathway and help in the prediction of the surgical outcome in canaloplasty. The mechanism for canaloplasty is not yet completely clarified; currently under discussion are circumferential viscodilation, permanent distension of the inner wall of Schlemm's canal using a suture and a Stegmann canal expander.

Suture Distension of Schlemm's Canal in Canaloplasty: An Anterior Segment Imaging Study.

Purpose. The object of this study was to investigate the role of the suture stent regarding its impact on reduction of intraocular pressure (IOP) in canaloplasty based on the distension of the inner wall of Schlemm's canal. Methods. Nineteen glaucoma patients who underwent canaloplasty with successful positioning of the tensioning suture were included. The measurements were analyzed using linear mixed models, with the means adjusted to IOP, age, cup-to-disc ratio, and time of follow-up. Results. Mean follow-up time was 27.6 months (SD 10.5). Mean intraocular pressure (IOP) was 24.6 mmHg (SD 5.29), 13.8 (SD 2.65), and 14.5 (SD 0.71) before surgery, at 12 months, and at 36 months after surgery, respectively. 57.9% of patients had no medication at last evaluation. Differences and variations of measurements between the devices over a time of 12 months were not significant (p = 0.15 to 0.98). Some angles of distension associated with the suture stent inside SC were predictive for IOP reduction (p < 0.03 to < 0.001), but not for final IOP (p = 0.64 to 0.96). Conclusion. The angles of the inner wall of Schlemm's canal generated by the suture stent were comparable between OCT and UBM and did not change significantly over time. There was a tendency towards a greater distension of Schlemm's canal, when the difference was larger between pre- and postoperative IOP, suggesting the tensioning suture may contribute to IOP reduction.

Prospective, noncomparative, nonrandomized case study of short-term outcomes of 360° suture trabeculotomy ab interno in patients with open-angle glaucoma.

BackgroundIn this paper, we describe 360° suture trabeculotomy (360°LOT) ab interno and the short-term course in patients who underwent this procedure.MethodsWe prospectively studied 12 patients (12 eyes) with open-angle glaucoma who underwent 360°LOT ab interno at the Sato Eye Clinic between February and July 2014. The surgical procedure involved making a 1.7 mm temporal corneal incision, exposing an approximately 15° opening in the inner wall of Schlemm’s canal (nasal side) using a Trabectome with a gonioscope, and inserting a 5-0 nylon suture rounded at the tip into Schlemm’s canal opened via the anterior chamber. The suture was then threaded around Schlemm’s canal, and the tip of the suture that emerged on the other side was then advanced through the opening to make a circumferential incision. Intraocular pressure (IOP), number of anti-glaucoma medications used, complications, and the surgery completion rate were prospectively studied.ResultsMean IOP, which was 19.4 mmHg at baseline, showed a significant decrease at each of the monthly observation points, reaching 13.8 mmHg at 6 months after surgery (P=0.0004, paired t-test). The mean number of anti-glaucoma medications decreased from 3.2 at baseline to 1.1 at 6 months after surgery. IOP spikes ≥30 mmHg were seen in 25% of patients, but there were no other serious complications and the surgery completion rate was 92%.ConclusionThe 360°LOT ab interno procedure preserves the conjunctiva and sclera, and has a high surgery completion rate when using the anterior chamber approach, and could therefore be an effective short-term treatment of open-angle glaucoma.

Finite element analysis of the pressure-induced deformation of Schlemm's canal endothelial cells.

The endothelial cells lining the inner wall of Schlemm's canal (SC) in the eye are relatively unique in that they support a basal-to-apical pressure gradient that causes these cells to deform, creating giant vacuoles and transendothelial pores through which the aqueous humor flows. Glaucoma is associated with an increased resistance to this flow. We used finite element modeling and estimates of cell modulus made using atomic force microscopy to characterize the pressure-induced deformation of SC cells and to estimate the maximum pressure drop that SC cells can support. We examined the effects of cell geometry, cell stiffness, and the contribution of the cell cortex to support the pressure-generated load. We found that the maximum strain generated by this loading occurs at the points of cell-substrate attachment and that the cortex of the cells bears nearly all of this load. The ability of these cells to support a significant transcellular pressure drop is extremely limited (on the order of 5mmHg or less) unless these cells either stiffen very considerably with increasing deformation or have substantial attachments to their substratum away from their periphery. This puts limits on the flow resistance that this layer can generate, which has implications regarding the site where the bulk of the flow resistance is generated in healthy and glaucomatous eyes.