scholarly journals Mechanical responsiveness of the endothelial cell of Schlemm's canal: scope, variability and its potential role in controlling aqueous humour outflow

2011 ◽  
Vol 9 (71) ◽  
pp. 1144-1155 ◽  
Author(s):  
E. H. Zhou ◽  
R. Krishnan ◽  
W. D. Stamer ◽  
K. M. Perkumas ◽  
K. Rajendran ◽  
...  

Primary open-angle glaucoma is associated with elevated intraocular pressure, which in turn is believed to result from impaired outflow of aqueous humour. Aqueous humour outflow passes mainly through the trabecular meshwork (TM) and then through pores formed in the endothelium of Schlemm's canal (SC), which experiences a basal-to-apical pressure gradient. This gradient dramatically deforms the SC endothelial cell and potentially contributes to the formation of those pores. However, mechanical properties of the SC cell are poorly defined. Using optical magnetic twisting cytometry and traction force microscopy, here we characterize the mechanical properties of primary cultures of the human SC cell, and for the first time, the scope of their changes in response to pharmacological agents that are known to modulate outflow resistance. Lysophosphatidic acid, sphingosine-1-phosphate (S1P) and thrombin caused an increase in cell stiffness by up to 200 per cent, whereas in most cell strains, exposure to latrunculin A, isoproterenol, dibutryl cyclic-AMP or Y-27632 caused a decrease in cell stiffness by up to 80 per cent, highlighting that SC cells possess a remarkably wide contractile scope. Drug responses were variable across donors. S1P, for example, caused 200 per cent stiffening in one donor strain but only 20 per cent stiffening in another. Isoproterenol caused dose-dependent softening in three donor strains but little or no response in two others, a finding mirrored by changes in traction forces and consistent with the level of expression of β 2 -adrenergic receptors. Despite donor variability, those drugs that typically increase outflow resistance systematically caused cell stiffness to increase, while in most cases, those drugs that typically decrease outflow resistance caused cell stiffness to decrease. These findings establish the endothelial cell of SC as a reactive but variable mechanical component of the aqueous humour outflow pathway. Although the mechanism and locus of increased outflow resistance remain unclear, these data suggest the SC endothelial cell to be a modulator of outflow resistance.

2021 ◽  
Vol 10 (3) ◽  
pp. 401
Author(s):  
Tomoki Sato ◽  
Takahiro Kawaji

We evaluated the effects of ripasudil on the distal aqueous outflow tract in patients with open-angle glaucoma (OAG) who underwent a 360° suture trabeculotomy ab interno followed by ripasudil treatment beginning 1 month postoperatively. We compared 27 of these patients, by using propensity score analysis, with 27 patients in a matched control group who had no ripasudil treatment. We assessed the changes in the mean intraocular pressure (IOP) and the relationship between the IOP changes and background factors. All eyes had a complete 360° Schlemm’s canal incision and phacoemulsification. The mean IOP at 1 and 3 months after ripasudil administration were significantly reduced by −1.7 ± 1.9 mmHg (p < 0.0001) and −1.3 ± 2.3 mmHg (p = 0.0081) in the ripasudil group, respectively, but IOP in the control group was not significantly reduced. The IOP reduction was significantly associated with the IOP before ripasudil treatment (p < 0.001). In conclusion, the use of ripasudil for patients with OAG after circumferential incision of the Schlemm’s canal produced significant IOP reductions. Ripasudil may affect the distal outflow tract, thereby leading to the IOP reduction.


2021 ◽  
Vol 10 (14) ◽  
pp. 3181
Author(s):  
Naoki Okada ◽  
Kazuyuki Hirooka ◽  
Hiromitsu Onoe ◽  
Yumiko Murakami ◽  
Hideaki Okumichi ◽  
...  

We compared surgical outcomes in patients with either primary open-angle glaucoma or exfoliation glaucoma after undergoing combined phacoemulsification with either a 120° or 180° incision during a Schlemm’s canal microhook ab interno trabeculotomy (μLOT-Phaco). This retrospective comparative case series examined 52 μLOT-Phaco eyes that underwent surgery between September 2017 and December 2020. Surgical qualified success was defined as an intraocular pressure (IOP) of ≤20 mmHg, ≥20% IOP reduction with IOP-lowering medications, and no additional glaucoma surgery. Success rates were evaluated by Kaplan-Meier survival analysis. The number of postoperative IOP-lowering medications and occurrence of complications were also assessed. Mean preoperative IOP in the 120° group was 16.9 ± 7.6 mmHg, which significantly decreased to 10.9 ± 2.7 mmHg (p < 0.01) and 11.1 ± 3.1 mmHg (p = 0.01) at 12 and 24 months, respectively. The mean number of preoperative IOP-lowering medications significantly decreased from 2.8 ± 1.4 to 1.4 ± 1.4 (p < 0.01) at 24 months. Mean preoperative IOP in the 180° group was 17.1 ± 7.0 mmHg, which significantly decreased to 12.1 ± 3.2 mmHg (p = 0.02) and 12.9 ± 1.4 mmHg (p = 0.01) at 12 and 24 months, respectively. The mean number of preoperative IOP-lowering medications significantly decreased from 2.9 ± 1.2 to 1.4 ± 1.5 (p < 0.01) at 24 months. The probability of qualified success at 24 months in the 120° and 180° groups was 50.4% and 54.6%, respectively (p = 0.58). There was no difference observed for hyphema formation or IOP spikes. Surgical outcomes were not significantly different between the 120° and 180° incisions in Schlemm’s canal.


2013 ◽  
Vol 54 (3) ◽  
pp. 1698 ◽  
Author(s):  
Vikas Gulati ◽  
Shan Fan ◽  
Cassandra L. Hays ◽  
Thomas W. Samuelson ◽  
Iqbal Ike K. Ahmed ◽  
...  

2017 ◽  
Vol 1 (3) ◽  
pp. 100-111
Author(s):  
Anup D. Pant ◽  
Larry Kagemann ◽  
Joel S. Schuman ◽  
Ian A. Sigal ◽  
Rouzbeh Amini

Aim/Purpose: Previous studies have shown that the trabecular meshwork (TM) is mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is believed that elevated TM stiffness increases resistance to the aqueous humor outflow, producing increased intraocular pressure (IOP).It would be advantageous to measure TM mechanical properties in vivo, as these properties are believed to play an important role in the pathophysiology of glaucoma and could be useful for identifying potential risk factors.  The purpose of this study was to develop a method to estimate in-vivo TM mechanical properties using clinically available exams and computer simulations.Design: Inverse finite element simulationMethods: A finite element model of the TM was constructed from optical coherence tomography (OCT) images of a healthy volunteer before and during IOP elevation. An axisymmetric model of the TM was then constructed. Images of the TM at a baseline IOP level of 11, and elevated level of 23 mmHg were treated as the undeformed and deformed configurations, respectively. An inverse modeling technique was subsequently used to estimate the TM shear modulus (G). An optimization technique was used to find the shear modulus that minimized the difference between Schlemm’s canal area in the in-vivo images and simulations.Results: Upon completion of inverse finite element modeling, the simulated area of the Schlemm’s canal changed from 8,889 μm2 to 2,088 μm2, similar to the experimentally measured areal change of the canal (from 8,889 μm2 to 2,100 μm2). The calculated value of shear modulus was found to be 1.93 kPa,  (implying an approximate Young’s modulus of 5.75 kPa), which is consistent with previous ex-vivo measurements.Conclusion: The combined imaging and computational simulation technique provides a unique approach to calculate the mechanical properties of the TM in vivo without any surgical intervention. Quantification of such mechanical properties will help us examine the mechanistic role of TM biomechanics in the regulation of IOP in healthy and glaucomatous eyes. 


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-Hye Park ◽  
Hyun Woo Chung ◽  
Eun Gyu Yoon ◽  
Min Jung Ji ◽  
Chungkwon Yoo ◽  
...  

AbstractGlaucoma treatment is usually initiated with topical medication that lowers the intraocular pressure (IOP) by reducing the aqueous production, enhancing the aqueous outflow, or both. However, the effect of topical IOP-lowering medications on the microstructures of the aqueous outflow pathway are relatively unknown. In this retrospective, observational study, 56 treatment-naïve patients with primary open-angle glaucoma were enrolled. Images of the nasal and temporal corneoscleral limbus were obtained using anterior segment optical coherence tomography (AS-OCT). The conjunctival vessels and iris anatomy were used as landmarks to select the same limbal area scan, and the trabecular meshwork (TM) width, TM thickness, and Schlemm’s canal (SC) area were measured before and after using the IOP-lowering agents for 3 months. Among the 56 patients enrolled, 33 patients used prostaglandin (PG) analogues, and 23 patients used dorzolamide/timolol fixed combination (DTFC). After 3 months of DTFC usage, the TM width, TM thickness, and SC area did not show significant changes in either the nasal or temporal sectors. Conversely, after prostaglandin analog usage, the TM thickness significantly increased, and the SC area significantly decreased (all P < 0.01). These findings warrant a deeper investigation into their relationship to aqueous outflow through the conventional and unconventional outflow pathways after treatment with PG analogues.


Author(s):  
Jianbo Zhou ◽  
Gregory T. Smedley

An ocular outflow model is proposed to theorize the effect of Schlemm’s canal (SC) and/or collector channel (CC) dilation combined with a trabecular bypass on elevated intraocular pressure (IOP) in glaucomatous eyes. The dilated height of the elliptic SC is largest at the bypass and linearly deceases to the non-dilated height over the dilated circumferential length. The CC dilation is modeled with a reduced outflow resistance of second order polynomial. Equations governing the pressure and flow in SC are solved numerically. The model predicts that the IOP is reduced substantially with moderate dilation from the normal 20 μm to 40 μm at the bypass. SC dilation is more effective for eyes with smaller SC. The dilation of CC can also significantly lower the IOP. With the trabecular bypass alone, the elevated IOP is expected to drop to the mid-to-high teens. The IOP can be further reduced by another 3 to 6 mmHg with moderate SC and CC dilation.


Ophthalmology ◽  
2015 ◽  
Vol 122 (7) ◽  
pp. 1283-1293 ◽  
Author(s):  
Norbert Pfeiffer ◽  
Julian Garcia-Feijoo ◽  
Jose M. Martinez-de-la-Casa ◽  
Jose M. Larrosa ◽  
Antonio Fea ◽  
...  

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