Schlemm\'s canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvβ3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced β-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin β3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvβ3 signaling to improve SC functionality.

OBJECTIVE: To perform an in vivo evaluation of the changes in Schlemm\'s canal (SC) among patients with primary angle-closure disease (PACD) using swept-source optical coherence tomography (SS-OCT).
METHODS: Patients diagnosed with PACD who had not undergone surgery were recruited. The SS-OCT quadrants scanned herein included the nasal and temporal sections at 3 and 9 o\'clock, respectively. The diameter and cross-sectional area of the SC were measured. A linear mixed-effects model was performed to analyze the effects of parameters on the SC changes. The hypothesis of interest was related to the angle status (iridotrabecular contact, ITC/open angle, OPN), which was further explored with pairwise comparisons of the estimated marginal means (EMMs) of the SC diameter and SC area. In the ITC regions, the relationship between the trabecular-iris contact length (TICL) percentage and SC parameters was also studied by a mixed model.
RESULTS: A total of 49 eyes of 35 patients were included for measurements and analysis. The percentage of observable SCs in the ITC regions was only 58.5% (24/41), whereas it was 86.0% (49/57) in the OPN regions (χ2 = 9.44, p = 0.002). ITC was significantly associated with a decreasing SC size. The EMMs for the diameter and cross-sectional area of SC at the ITC and OPN regions were 203.34 μm versus 261.41 μm (p = 0.006) and 3174.43 μm2 versus 5347.63 μm2 (p = 0.022), respectively. Sex, age, spherical equivalent refraction, intraocular pressure, axial length, extent of angle closure, history of acute attack and treatment with LPI were not significantly associated with SC parameters. In the ITC regions, a larger TICL percentage was significantly associated with a decrease in SC diameter and area (p = 0.003 and 0.019, respectively).
CONCLUSIONS: The morphologies of SC could be affected by the angle status (ITC/OPN) in patients with PACD, and ITC was significantly associated with a decreasing SC size. These changes in SC as described by OCT scans might help to elucidate the progression mechanisms of PACD.

BACKGROUND: The purpose of this study was to establish a novel and reversible experimental ocular hypertension primate model by blocking Schlemm\'s canal.
METHODS: A model was induced in adult cynomolgus monkeys (n = 4) by blocking Schlemm\'s canal with an inserted microcatheter (200 μm diameter); it was removed 6 weeks later from one monkey to reverse the elevated intraocular hypertension. All animals were monitored for 11 months; weekly measurements of intraocular pressure and biweekly examinations with spectral domain optical coherence tomography and disc photography were performed. Histopathology of the eye and retinal ganglion cell counts were completed at the end of the study.
RESULTS: The intraocular pressure of the blocked eyes was significantly higher than that of the contralateral eyes at 1 month after the blockage (p < 0.001); the mean intraocular pressure was similar to the contralateral eye from 1 week to 11 months after the microcatheter was removed in monkey A (p = 0.170). The mean intraocular pressure of the blocked eyes of the remaining monkeys was significantly higher than that of the contralateral eyes throughout the follow-up period (p < 0.001). The fundus imaging showed decreases in the retinal nerve fibre layer thickness, and localized defects were observed in two blocked eyes. A histological examination demonstrated that the number of retinal ganglion cells in the blocked eyes of monkeys A, B, and C was significantly decreased compared with the control.
CONCLUSIONS: Schlemm\'s canal blockage alone in the monkey model produces sustained elevation of intraocular pressure, which presents a novel animal model for studying the pathogenesis of glaucoma.

暂无摘要。

UNASSIGNED: This study aimed to investigate the clinical application of laser as a knife in Ab externo Schlemm\'s canal (SC) surgery and compare the efficacy and safety of the CO2 laser with the conventional procedure using a surgical knife.
UNASSIGNED: Patients who underwent either canaloplasty or trabeculotomy with CO2 laser system which was used to locate and ablate the outer wall of SC at the time interval between May 2020 and May 2021 were identified, their medical files were reviewed, and their results were compared with conventional surgery group who underwent canaloplasty or trabeculotomy with conventional surgical knife at the same time period. The following datas were conducted and compared: age, sex, intraocular pressure (IOP), number of drugs, best-corrected visual acuity (BCVA), mean deviation and pattern standard deviation of visual field examination, SC opening related complications.
UNASSIGNED: A total of 49 patients (49 eyes) were included in this study, including 23 in the Laser surgery group and 26 in the conventional surgery group. Time for SC opening was 49.33 ± 25.23 s and 116.50 ± 31.79 s for laser surgery group and conventional surgery group, respectively. This difference between the two groups was statistically significant (P < 0.01). Hemorrhage occurred in five eyes during ablation for the laser surgery group and in 24 eyes for the conventional surgery group. In addition, anterior chamber penetration occurred in two cases for the laser surgery group and in six cases for the conventional surgery group. The success rate of identifying and opening outer wall of SC was 91.30% (21 eyes) for the laser surgery group and 76.92% (20 eyes) for the conventional surgery group. The difference between preoperative and postoperative intraocular pressure for each group was statistically significant (P < 0.01), and there were no statistically significant differences across the two groups in terms of postoperative IOP (P = 0.238) and BCVA (P = 0.389).
UNASSIGNED: Compared with the conventional procedure using a surgical knife, CO2 laser-assisted ablation of the outer wall of SC was less time-consuming and less technically challenging. CO2 laser-assisted ablation also resulted in fewer complications. Furthermore, it had a shorter learning curve and a higher success rate of identifying and opening SC.

OBJECTIVE: To observe the changes in Schlemm\'s canal (SC), trabecular meshwork (TM), and anterior chamber relevant parameters after small incision lenticule extraction (SMILE) of myopia patients.
METHODS: A total of 58 eyes from 30 patients who underwent SMILE were divided into a low and moderate myopia group (group A, 32 eyes) and a high myopia group (group B, 26 eyes). The diameter and area of the SC, the width and thickness of TM obtained by CIRRUS HD-OCT5000, and the related anterior chamber parameters obtained by Pentacam anterior segment analysis system, accommodation amplitude (AMP) were observed pre- and postoperatively. The preoperative intraocular pressure (IOP) and postoperative correction of intraocular pressure (IOPcc) were measured.
RESULTS: The diameter and area of the SC in the two groups were significantly increased postoperatively (all P<0.01). The TM width of the patients in the two groups were increased at 1mo after surgery (both P<0.01), but the TM thickness did not change (P>0.05). The corneal curvature, central anterior chamber depth, and anterior chamber volume decreased after SMILE surgery (all P<0.01). There was a weak negative correlation between the SC area change and AMP change in group A (r=-0.362, P<0.01). The postoperative IOP decreased after correction by Shah formula (P<0.05).
CONCLUSIONS: SC and TM in myopia patients change in the early postoperative stage of SMILE and the IOP is decline.

OBJECTIVE: To evaluate the ocular outcomes and to elucidate possible mechanisms underlying intraocular pressure (IOP) change following the head-down tilt (HDT) test.
METHODS: The study included 21 participants at the Department of Ophthalmology of Tongji Hospital. Subjects received the test of I-care tonometry, enhanced depth imaging optical coherence tomography and heart rate variability (HRV) analysis before and after 15min HDT test. The lumen area of Schlemm\'s canal (SCAR), IOP, HRV were calculated.
RESULTS: IOP increased significantly after 20° head down position from 14.0±3.0 to 17.0±3.3 mm Hg (P<0.001). SCAR decreased from 13449.0±5454.9 µm2 at sitting condition to 9576.6±4130.9 µm2 post 15min HDT test. High frequency (HF) indices increased significantly from 1462±865 Hz at baseline to 2128±824 Hz. Heart rate (HR) decreased significantly from 76±11.48 to 70±11.52 bpm after the HDT. The linear regression analysis showed that the difference of HF and SCAR significantly correlated with each other during the HDT (R2 =20%, P=0.04).
CONCLUSIONS: These outcomes perform the first evidence of the activation of autonomic nervous system of HDT may cause the collapse of Schlemm\'s canal lumen, which in turn leading to the increased IOP.

OBJECTIVE: Elevated intraocular pressure is primarily induced by the increased resistance of conventional outflow of aqueous humor. Dysfunction of the juxtacanalicular region of trabecular meshwork (TM) and Schlemm\'s canal (SC) endothelium, as the main conventional outflow tissue, have been implicated as the major reasons for the increased resistance. Integrins are widespread in these tissues, especially alpha8 integrin (ITGA8). We aim to investigate the properties of cells expressing ITGA8 in the conventional outflow tissue.
METHODS: Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to detect the mRNA and protein levels of ITGA8 in human conventional outflow tissue. ITGA8-positive cells were isolated from the cultured human TM cells through a magnetic bead-based approach. Flow Cytometry was used to determine the purification efficiency. The expressions of TM and SC biomarkers and dexamethasone-induced myocilin secretion capacity of ITGA8-positive cells was assessed by Real-time PCR, IF and Western blot. A gel contraction assay was performed to evaluate contractility of ITGA8-positive cells after endothelin 1 treatment.
RESULTS: ITGA8 was found with robust expression near the inner wall of SC endothelium. After purification, the proportion of ITGA8-positive cells were increased by about 10%. ITGA8-positive cells were identified with the properties as SC endothelial cells, such as more robust expressions of SC biomarkers, less dexamethasone-inducible myocilin expression, and stronger contractility.
CONCLUSIONS: This study demonstrated that cells expressing ITGA8 in SC region possess more properties as SC endothelial cells. Our data implicate a crucial role of ITGA8 in aqueous humor (AH) outflow resistance regulation.

Schlemm\'s canal (SC) is a ring structure responsible for maintaining fluid homeostasis in the anterior chamber of the eye by draining aqueous humor (AH) from the trabecular meshwork (TM) into the collecting channel (CC). Obstruction of the AH flow in this conventional pathway leads to an elevation of intraocular pressure in glaucoma, which is internationally recognized as the most common cause of blindness. Although there are obvious morphological differences between patients and healthy individuals, the AH drainage capacity of SC with specific parameters is difficult to quantitatively evaluate due to the limitations of analyses or experimental technologies. In this paper, the AH flow dynamic features under various SC morphological parameters are studied by numerical simulations of 3D models. The axis length of the SC cross-section and the level of openness are chosen as the main morphological factors according to the clinical data. The flow features, including the velocity, streamline and wall shear stress, are analyzed. This study aimed not only to explore the feasibility of 3D numerical modeling in evaluating the SC drainage capacity, but also to reveal the relationship between SC morphological parameters and the dynamic features of AH drainage.

Aerobic exercise (AE) has been reported to decrease intraocular pressure (IOP) in healthy subjects and there are concomitant morphological changes in the anterior segment of the eye including the Schlemm\'s canal (SC). However, its effects on IOP and SC morphology in glaucoma patients had not been studied before. We aim to investigate the effect of AE on the IOP and SC dimension in both healthy and primary open-angle glaucoma (POAG) eyes.
The area and diameter of SC and IOP were measured in 35 primary open-angle glaucoma (POAG) patients (59 eyes) and 36 healthy subjects (72 eyes) before and after performing moderate intensity of AE by running on a treadmill for 30 min. SC was imaged by swept-source optical coherence tomography (SS-OCT) for evaluation.
In comparison with baseline values, mean IOP decreased significantly following AE in both POAG and healthy eyes (both P < 0.001), in which POAG eyes showed a greater degree of reduction compared to healthy eyes (P = 0.002). In comparison with baseline values, in both POAG and healthy eyes, the average cross-sectional area (POAG: 80.48 +/- 59.54 vs. 99.20 +/- 54.87 pixels; healthy: 151.84 +/- 52.76 vs. 198.23 +/- 53.70 pixels; both P < 0.001) and diameter (POAG: 3.73 +/- 1.69 vs. 4.33 +/- 1.74 pixels; healthy: 5.61 +/- 1.02 vs. 6.47 +/- 1.20 pixels; both P < 0.001) of SC significantly increased after AE. In POAG, both treated and untreated with IOP-lowering medications, a significant reduction in mean IOP and increase in SC dimensions following AE were observed (all P < 0.05), and there were no significant differences of such measurements between the two subgroups (all P > 0.05).
AE-induced reduction in IOP and an increase in SC dimensions in POAG eyes as in healthy eyes. Further studies to evaluate the long-term effect of AE on IOP control and SC morphology in POAG seem warranted.