scholarly journals Trabecular meshwork's collagen network formation is inhibited by non‐pigmented ciliary epithelium‐derived extracellular vesicles

Author(s):  
Saray Tabak ◽  
Sofia Schreiber‐Avissar ◽  
Elie Beit‐Yannai
2006 ◽  
Vol 14 ◽  
pp. S35
Author(s):  
Y.M. Jenniskens ◽  
W. Koevoet ◽  
A.C. De Bart ◽  
J.A. Verhaar ◽  
H. Weinans ◽  
...  

2020 ◽  
Vol 21 (17) ◽  
pp. 6105 ◽  
Author(s):  
Natalie Lerner ◽  
Itay Chen ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai

The importance of extracellular vesicles (EVs) as signaling mediators has been emphasized for several pathways with only limited data regarding their role as protective messages during oxidative stress (OS). The ocular drainage system is unique by being continuously exposed to OS and having a one-way flow of the aqueous humor carrying EVs taking role in glaucoma disease. Here, we aimed to examine the ability of EVs derived from the non-pigmented ciliary epithelium (NPCE)—the aqueous humor producing cells exposed to OS—to deliver protecting messages to the trabecular meshwork (TM)—the aqueous humor draining cells—a process with significance to the pathophysiology of glaucoma disease. EVs extracted from media of NPCE cells exposed to non-lethal OS and their unstressed control were incubated with TM cells. The effects of EVs derived from oxidative stressed cells on the activation of the nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 (Nrf2-Keap1), a major OS pathway, and of the Wnt pathway, known for its role in primary open-angle glaucoma, were evaluated. EVs derived from oxidized NPCE cells significantly protected TM cells from direct OS. The TM cells uptake of EVs from oxidized NPCE and their cytosolic Nrf2 levels were significantly higher at 8 h post-exposure. EVs derived from oxidized NPCE cells significantly attenuated Wnt protein expression in TM cells and activated major antioxidant genes as measured by qRT-PCR. TM cells exposed to EVs derived from oxidized NPCE cells exhibited significantly lower OS and higher super oxide dismutase and catalase activity. Finally, we were able to show that carbonylated proteins and products of oxidized protein are presented in significantly higher levels in EVs derived from oxidized NPCE cells, supporting their suggested role in the signaling process. We hypothesize that these findings may have implications beyond understanding the pathophysiology of glaucoma disease and that transmitting signals that activate the antioxidant system in target cells represent a broad response common to many tissues communication.


2019 ◽  
Vol 400 (5) ◽  
pp. 565-574 ◽  
Author(s):  
Yuexin Wu ◽  
Gaoxiang Ge

Abstract Collagens form complex networks in the extracellular space that provide structural support and signaling cues to cells. Network-forming type IV collagens are the key structural components of basement membranes. In this review, we discuss how the complexity of type IV collagen networks is established, focusing on collagen α chain selection in type IV collagen protomer and network formation; covalent crosslinking in type IV collagen network stabilization; and the differences between solid-state type IV collagen in the extracellular matrix and soluble type IV collagen fragments. We further discuss how complex type IV collagen networks exert their physiological and pathological functions through cell surface integrin and nonintegrin receptors.


2009 ◽  
Vol 379 (2) ◽  
pp. 222-226 ◽  
Author(s):  
Yvonne M. Bastiaansen-Jenniskens ◽  
Wendy Koevoet ◽  
Kaspar M.B. Jansen ◽  
Jan A.N. Verhaar ◽  
Jeroen DeGroot ◽  
...  

ChemInform ◽  
2010 ◽  
Vol 31 (11) ◽  
pp. no-no
Author(s):  
Hirokazu Sudo ◽  
Kaori Kijima ◽  
Hideaki Otsuka ◽  
Toshinori Ide ◽  
Eiji Hirata ◽  
...  

2021 ◽  
Vol 14 (9) ◽  
pp. 858
Author(s):  
Saray Tabak ◽  
Valeria Feinshtein ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai

Primary open-angle glaucoma is established by the disruption of trabecular meshwork (TM) function. The disruption leads to increased resistance to the aqueous humor (AH), generated by the non-pigmented ciliary epithelium (NPCE). Extracellular vesicles (EVs) participate in the communication between the NPCE and the TM tissue in the ocular drainage system. The potential use of NPCE-derived EVs to deliver siRNA to TM cells has scarcely been explored. NPCE-derived EVs were isolated and loaded with anti-fibrotic (SMAD7) siRNA. EV’s structural integrity and siRNA loading efficiency were estimated via electron microscopy and fluorescence. Engineered EVs were added to pre-cultured TM cells and qRT-PCR was used to verify the transfer of selected siRNA to the cells. Western blot analysis was used to evaluate the qualitative effects on Wnt-TGFβ2 proteins’ expression. EVs loaded with exogenous siRNA achieved a 53% mRNA knockdown of SMAD7 in TM cells, resulting in a significant elevation in the levels of β-Catenin, pGSK3β, N-Cadherin, K-Cadherin, and TGFβ2 proteins in TM cells. NPCE-derived EVs can be used for efficient siRNA molecule delivery into TM cells, which may prove to be beneficial as a therapeutic target to lower intraocular pressure (IOP).


1999 ◽  
Vol 47 (9) ◽  
pp. 1341-1343 ◽  
Author(s):  
Hirokazu SUDO ◽  
Kaori KIJIMA(nee YUASA) ◽  
Hideaki OTSUKA ◽  
Toshinori IDE ◽  
Eiji HIRATA ◽  
...  

2008 ◽  
Vol 16 ◽  
pp. S22
Author(s):  
Y.M. Bastiaansen-Jenniskens ◽  
W. Koevoet ◽  
K.M. Jansen ◽  
J.A. Verhaar ◽  
J. DeGroot ◽  
...  

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