Hyperbranched Cationic Glycogen Derivative-Mediated IκBα Gene Silencing Regulates the Uveoscleral Outflow Pathway in Rats
Joint Authors
Zeng, Rui
Li, Jinmiao
Gong, Haijun
Luo, Jiahao
Li, Zijing
Ou, Zhaoxing
Zhang, Si
Yang, Liqun
Lan, Yuqing
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-12-18
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
The role of the IκB/NF-κB signaling pathway in the uveoscleral outflow pathway was investigated with IκBα gene silencing mediated by the 3-(dimethylamino)-1-propylamine-conjugated glycogen (DMAPA-Glyp) derivative.
The IκBα-siRNA-loaded DMAPA-Glyp complex was transfected into the ciliary muscles of rats by intracameral injection (labeled as the DMAPA-Glyp+siRNA group).
The Lipofectamine™ 2000 (Lipo)/siRNA complex and the naked siRNA were set as the controls.
The mRNA and protein expression of IκBα, NF-κBp65, and MMP-2 were analyzed by real-time PCR, western blotting, and in situ gelatin zymography.
Nuclear translocation of NF-κBp65 was analyzed by immunofluorescence.
Rat intraocular pressure (IOP) was monitored pre- and postinjection.
Gene transfection efficiency and toxicity of the DMAPA-Glyp derivative were also evaluated.
After RNA interference (RNAi), IκBα mRNA and protein expression were significantly inhibited.
NF-κBp65 mRNA and protein expression showed no significant differences.
Nevertheless, nuclear translocation of NF-κBp65 occurred in the DMAPA-Glyp+siRNA group.
Both mRNA expression and activity of MMP-2 increased, with the largest increase in the DMAPA-Glyp+siRNA group.
IOP in the DMAPA-Glyp+siRNA group fell to the lowest level on day 3 after RNAi.
The levels of Cy3-siRNA in the ciliary muscle of the DMAPA-Glyp+siRNA group did not significantly decrease over time.
At 7 and 14 d after RNAi, no significant pathological damage was detectable in the eyes injected with the DMAPA-Glyp derivative or the DMAPA-Glyp/siRNA complex.
Taken together, our results suggest that downregulation of IκBα expression in the ciliary muscle plays a crucial role in reducing the IOP values of rats.
IκBα may become a new molecular target for lowering IOP in glaucoma.
The DMAPA-Glyp derivative is safe and feasible as an effective siRNA vector in rat eyes.
American Psychological Association (APA)
Zeng, Rui& Li, Jinmiao& Gong, Haijun& Luo, Jiahao& Li, Zijing& Ou, Zhaoxing…[et al.]. 2020. Hyperbranched Cationic Glycogen Derivative-Mediated IκBα Gene Silencing Regulates the Uveoscleral Outflow Pathway in Rats. BioMed Research International،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1137354
Modern Language Association (MLA)
Zeng, Rui…[et al.]. Hyperbranched Cationic Glycogen Derivative-Mediated IκBα Gene Silencing Regulates the Uveoscleral Outflow Pathway in Rats. BioMed Research International No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1137354
American Medical Association (AMA)
Zeng, Rui& Li, Jinmiao& Gong, Haijun& Luo, Jiahao& Li, Zijing& Ou, Zhaoxing…[et al.]. Hyperbranched Cationic Glycogen Derivative-Mediated IκBα Gene Silencing Regulates the Uveoscleral Outflow Pathway in Rats. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1137354
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1137354