Trabecular Meshwork Schlemm's Canal Research Articles

To discuss the minimally invasive glaucoma surgery related to trabeculotomy from the perspective of physiological function of trabecular meshwork drainage pathway

The advent of minimally invasive glaucoma surgery (MIGS) has broadened the therapeutic options for managing glaucoma. In recent years, MIGS procedures targeting the trabecular meshwork-Schlemm's canal aqueous outflow resistance site have garnered significant attention. This focus has extended to the pathophysiological changes occurring within the aqueous outflow pathway. However, questions persist regarding the efficacy of near-peripheral or peripheral trabeculotomy in achieving the anticipated reduction of outflow resistance and the suitability of MIGS surgery for patients with primary open-angle glaucoma. By integrating clinical experience with pertinent clinical research, this paper advocates for a reevaluation of MIGS procedures to aid clinicians in making informed decisions regarding various glaucoma surgical interventions.

Integrin Crosstalk and Its Effect on the Biological Functions of the Trabecular Meshwork/Schlemm’s Canal

Integrins are a family of heterodimeric receptors composed of an α- and β-subunit that mediate cell-adhesion to a number of extracellular matrix (ECM) proteins in the Trabecular Meshwork/Schlemm’s canal (TM/SC) of the eye. Upon binding an ECM ligand, integrins transmit signals that activate a number of signaling pathways responsible for regulating actin-mediated processes (i.e phagocytosis, cell contractility, and fibronectin fibrillogenesis) that play an important role in regulating intraocular pressure (IOP) and may be involved in glaucoma. An important function of integrin-mediated signaling events is that the activity of one integrin can affect the activity of other integrins in the same cell. This creates a crosstalk that allows TM/SC cells to respond to changes in the ECM presumably induced by the mechanical forces on the TM/SC, aging and disease. In this review, we discuss how integrin crosstalk influences the function of the human TM/SC pathway. In particular, we will discuss how different crosstalk pathways mediated by either the αvβ3 or α4β1 integrins can play opposing roles in the TM when active and therefore act as on/off switches to modulate the cytoskeleton-mediated processes that regulate the outflow of aqueous humor through the TM/SC.

Efficacy and safety of adding ripasudil to existing treatment regimens for reducing intraocular pressure.

Ripasudil accelerates aqueous humour drainage along the trabecular meshwork-Schlemm's canal route and has been approved for clinical use in Japan. We retrospectively investigated the efficacy and safety of adding ripasudil to existing treatment regimens to reduce intraocular pressure (IOP) in patients with glaucoma. A total of 119 eyes from 119 subjects (61 men, 58 women) with primary open-angle glaucoma or ocular hypertension who had ripasudil added to their treatment regimens between December 2014 and June 2015 were included. An average of 3.8±1.0 anti-glaucoma medications was in use before adding ripasudil. Subjects were divided into four groups based on the number of medications included in the original treatment regimen: ≤2, 3, 4, or ≥5 medications. The IOP was compared before and after 1 and 3 months of treatment with ripasudil for all subjects and between groups. Patients for whom ripasudil use was discontinued within 3months were also examined. The IOP was significantly lower in all patients after 1month (17.5±4.5mmHg) and 3months (16.8±4.2mmHg) of treatment than it was before (19.8±5.3mmHg, p<0.0001). All groups were equivalent in the rate and magnitude of IOP change. Ripasudil administration was discontinued in five patients (4.2%) prior to the end of the study: three were lost to follow-up and two underwent glaucoma surgery. Adding ripasudil to existing glaucoma treatment regimens is effective and safe in reducing IOP, regardless of the number of medications in use.

Mathematical Modeling of Outflow Facility Increase With Trabecular Meshwork Bypass and Schlemm Canal Dilation.

To mathematically model the conventional aqueous humor outflow system with trabecular meshwork (TM) bypass and Schlemm canal (SC) dilation. The SC was modeled as a rectangular channel with the TM modeled as a permeable membrane. The collector channels (CCs) were modeled as fluid sinks distributed along the outer wall of SC. Two different implants were investigated in this study. The Hydrus Microstent (scaffold) was modeled with a TM bypass and a dilated region in SC that was 7 or 15 mm long and approximately 5-fold larger than the normal height of SC (h0). The iStent trabecular microbypass was modeled with a similar structure except that the dilated region in SC was 1 mm long and 25% larger than h0. Creation of a TM bypass structure would increase the pressure in the surrounding regions inside the SC and make it close to the intraocular pressure. SC dilation would increase the pressure more uniformly in the dilated region. The pressure increase led to higher flow rates in SC and CCs, and subsequently increased outflow facility (C). If CCs were uniformly distributed, the increase in C was the smallest after implantation of 1 microbypass, compared with that after implantation of 2 microbypasses or 1 scaffold. If CCs were nonuniformly distributed, the magnitude of increase in C was sensitive to the location of implant, and the sensitivity was higher for the microbypass than the scaffold. The study showed that creation of TM bypass and SC dilation significantly increased outflow facility, and the amount of increase correlated with the length of dilated regions in SC.

Adenosine 3′,5′-cyclic-monophosphate and outflow facility in monkey eyes with intact and retrodisplaced ciliary muscle

Bolus intracameral infusion of 100 micrograms cAMP, corresponding to an initial intracameral concentration of 3 mM, significantly increased total outflow facility in cynomolgus monkey eyes with intact or disinserted-retrodisplaced ciliary muscles by 41% and 37% respectively. Lower cAMP doses had little or no effect in both types of eyes, as did dibutyryl cAMP doses of 1-100 micrograms (20 microM-2mM). In eyes with intact ciliary muscles, intracameral infusion (1 and 10 micrograms) of the cAMP analog 8-methylthio cAMP (0.25 mM and 2.5 mM) significantly increased facility by 55% and 69% respectively, while 100 micrograms of the inactive cAMP metabolite 5'AMP (3 mM) did not alter facility. The facility increases produced by cAMP and 8-methylthio cAMP represented a constant percentage of starting facility independent of the absolute value of starting facility. These findings indicate that the facility increase produced by cAMP and appropriate analogs is not mediated by ciliary-muscle contraction and that the disinsertion procedure itself does not compromise the ability of the outflow pathways to respond to cAMP. The facility increase probably represents a cAMP effect directly on the endothelial cells of the trabecular meshwork-Schlemm's canal inner wall.

Glaucoma in Sturge-Weber Syndrome

Trabeculectomy specimens from three eyes with Sturge-Weber syndrome were examined histopathologically. Changes in the trabecular meshwork-Schlemm's canal system were similar to findings in old age and in primary open-angle glaucoma. Two mechanisms for glaucoma are theorized. In cases with buphthalmos and congenital glaucoma, the chamber angle is often anomalous, as in other types of congenital glaucoma. In later onset juvenile cases, the chamber angle more often appears normal. A premature aging of the trabecular meshwork Schlemm's canal complex, as shown by us histopathologically, is a primary cause of juvenile glaucoma. It is suggested that both mechanisms relate to the abnormal hemodynamics of episclera and chamber angle, due to persistance of Streeter's primordial vascular plexus.