Differential P1-purinergic modulation of human Schlemm's canal inner-wall cells

2005 ◽  
Vol 288 (4) ◽  
pp. C784-C794 ◽  
Author(s):  
Mike O. Karl ◽  
Johannes C. Fleischhauer ◽  
W. Daniel Stamer ◽  
Kim Peterson-Yantorno ◽  
Claire H. Mitchell ◽  
...  

Intraocular pressure is directly dependent on aqueous humor flow into, and resistance to flow out of, the eye. Adenosine has complex effects on intraocular pressure. Stimulation of A1and A2Aadenosine receptors changes intraocular pressure oppositely, likely through opposing actions on the outflow of aqueous humor. While the cellular sites regulating outflow resistance are unknown, the cells lining the inner wall of Schlemm's canal (SC) are a likely regulatory site. We applied selective adenosine receptor agonists to SC cells in vitro to compare the responses to A1and A2Astimulation. Parallel studies were conducted with human inner-wall SC cells isolated by a novel enzyme-assisted technique and with cannula-derived mixed inner- and outer-wall SC cells. A1agonists increased whole cell currents of both inner-wall and cannula-derived SC cells. An A2Aagonist reduced currents most consistently in specifically inner-wall SC cells. Those currents were also increased by A2B, but not consistently affected by A3, stimulation. A1, A2A, and A3agonists all increased SC-cell intracellular Ca2+. The electrophysiological results are consistent with the possibility that inner-wall SC cells may mediate the previously reported modulatory effects of adenosine on outflow resistance. The results are also consistent with the presence of functional A2B, as well as A1, A2A, and A3adenosine receptors in SC cells.

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.


Author(s):  
Annelies W. de Kater ◽  
R. Rand Allingham ◽  
Doug S. Bowman ◽  
Fredric S. Fay

Aqueous humor exits the anterior chamber of the eye through the trabecular meshwork into Schlemm's canal, a vessel which drains into the systemic circulatory system. The aqueous humor crosses the endothelial lining of Schlemm's canal by means of focal invaginations which form pores and allow digress of fluid into the canal. The trabecular meshwork provides a resistance to fluid flow resulting in a physiologic intraocular pressure in normal eyes. The region adjacent to Schlemm's canal appears to be the site of highest resistance to fluid flow in both normal and glaucomatous eyes. In eyes with primary open angle glaucoma (POAG) the resistance to fluid flow through the trabecular meshwork is abnormally high, causing an elevated intraocular pressure (IOP), which can lead to irreversible damage of the optic nerve and blindness. A definitive morphologic correlate of this disease has not been discovered. Immunohistochemical studies localizing fibronectin in unfixed frozen sections of human eyes have shown elevated levels of fibronectin in the eyes with glaucoma, however the specific distribution of this protein has not been determined due to poor tissue preservation.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mariela Subileau ◽  
Niyazi Acar ◽  
Alison Carret ◽  
Lionel Bretillon ◽  
Isabelle Vilgrain ◽  
...  

Abstract Aqueous humor drainage is essential for the regulation of intraocular pressure (IOP), a major risk factor for glaucoma. The Schlemm’s canal and the non-conventional uveoscleral pathway are known to drain aqueous humor from the eye anterior chamber. It has recently been reported that lymphatic vessels are involved in this process, and that the Schlemm’s canal responds to some lymphatic regulators. We have previously shown a critical role for bone morphogenetic protein 9 (BMP9) in lymphatic vessel maturation and valve formation, with repercussions in drainage efficiency. Here, we imaged eye lymphatic vessels and analyzed the consequences of Bmp9 (Gdf2) gene invalidation. A network of lymphatic vessel hyaluronan receptor 1 (LYVE-1)-positive lymphatic vessels was observed in the corneolimbus and the conjunctiva. In contrast, LYVE-1-positive cells present in the ciliary bodies were belonging to the macrophage lineage. Although enlarged conjunctival lymphatic trunks and a reduced valve number were observed in Bmp9-KO mice, there were no morphological differences in the Schlemm’s canal compared to wild type animals. Moreover, there were no functional consequences on IOP in both basal control conditions and after laser-induced ocular hypertonia. Thus, the BMP9-activated signaling pathway does not constitute a wise target for new glaucoma therapeutic strategies.


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

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):  
Andrew C. Crichton

Nonpenetrating glaucoma surgery encompasses techniques that involve a deep dissection to the level of Descemet’s membrane, allowing aqueous seepage. The major techniques covered by the term “nonpenetrating surgery” are deep sclerectomy with or without implant and viscocanalostomy. In large meta-analyses comparing nonpenetrating procedures to trabeculectomy, trabeculectomy resulted in lower intraocular pressures (IOP) but a higher risk of postoperative complications. Although nonpenetrating surgery is successful in lowering IOP, the amount of IOP lowering is typically not as low as can be achieved with trabeculectomy. Consequently, patient selection with regard to the target IOP is important in the decision of whether or not to perform a nonpenetrating procedure. The goal of nonpenetrating procedures is to lower IOP with fewer complications than are seen with trabeculectomy. The complications that can occur can be easily understood and predicted by an understanding of the techniques and modifications, as well as knowledge and mechanisms of the adjustments that can be used postoperatively to enhance success. After appropriate anesthetic, the techniques involve a deep dissection in the sclera to the limbus. In the case of deep sclerectomy, after the initial half-thickness flap is fashioned, a second deeper flap is created and excised. This dissection is taken to the level of Descemet’s membrane, allowing controlled flow of aqueous. A fine forceps may be used to strip the outer wall of Schlemm’s canal, further enhancing the flow. The space created by the excision can then be filled with an implant, such as collagen (AquaFlow™ Collagen Glaucoma Drainage Device; STAAR® Surgical Company, Monrovia, California) or hyaluronate (SK Gel®; Corneal Laboratories, Paris, France). For viscocanalostomy, Schlemm’s canal is identified and dilated by using viscoelastic. With deep sclerectomy, intraoperative or postoperative antimetabolites may be used to try to increase success rates by limiting the inflammatory response. Goniopuncture to the Descemet’s window is often required postoperatively (in up to 67% of cases) to enhance flow and lower IOP. The available evidence on complications of nonpenetrating glaucoma surgery is relatively sparse and may be challenging to interpret. Comparative studies between trabeculectomy and nonpenetrating surgery would seem to show fewer complications in the nonpenetrating group.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wei Chen ◽  
Zhiqi Chen ◽  
Yan Xiang ◽  
Chaohua Deng ◽  
Hong Zhang ◽  
...  

AbstractThis study aimed to investigate changes in Schlemm’s canal, intraocular pressure and ocular blood circulation following the activation of the sympathetic nervous system. Twenty healthy volunteers were enrolled in this study. The cold pressor test (CPT) was adopted. Cross-sectional area of Schlemm’s canal (SCAR), superficial and deep retinal vessel densities (s-RVD;d-RVD), pupil diameter (PD), intraocular pressure (IOP), mean ocular perfusion pressure (MOPP) and heart rate variability (HRV) were measured at three time-points: baseline (T0) and 5 min (T1) and 10 min (T2) after the CPT. After cold stimulation, LF/HF index (the ratio of low frenquency and high frenquency) increased significantly. IOP decreased from 16.9 ± 1.9 mmHg at baseline to 16.4 ± 2.7 mmHg at T1 and to 15.2 ± 2.7 mmHg at T2. The nasal cross-sectional area of SCAR (SCAR-n) increased from 6283.9 ± 2696.2 µm2 at baseline to 8392.9 ± 3258.7 µm2 at T1 and to 10422.0 ± 3643.8 µm2 at T2. The temporal cross-sectional area of SCAR (SCAR-t) increased from 6414.5 ± 2218.7 µm2 at baseline to 8610.8 ± 2317.1 µm2 at T1 and to 11544.0 ± 4129.2 µm2 at T2. The expansion of Schlemm’s canal was observed after the CPT might be caused by sympathetic nerve stimulation, subsequently leading to decreased IOP.


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