Polymeric micelle gene delivery of bcl-XL via eye drop reduced corneal apoptosis following epithelial debridement

Stromal keratocyte apoptosis triggered by epithelial injury is one mechanism of corneal disorders. A model of epithelial injury by epithelial debridement is established, and keratocyte apoptosis is evidenced by DNA fragmentation and cellular morphological changes in the anterior stroma underlying th...

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Veröffentlicht in:Journal of controlled release 2010-10, Vol.147 (1), p.76-83
Hauptverfasser: TONG, Yaw-Chong, CHANG, Shwu-Fen, KAO, Winston W.-Y, LIU, Chia-Yang, LIAW, Jiahorng
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container_issue 1
container_start_page 76
container_title Journal of controlled release
container_volume 147
creator TONG, Yaw-Chong
CHANG, Shwu-Fen
KAO, Winston W.-Y
LIU, Chia-Yang
LIAW, Jiahorng
description Stromal keratocyte apoptosis triggered by epithelial injury is one mechanism of corneal disorders. A model of epithelial injury by epithelial debridement is established, and keratocyte apoptosis is evidenced by DNA fragmentation and cellular morphological changes in the anterior stroma underlying the injured epithelium. Delivery of plasmid (pCMV-bcl-x(L)-eGFP) encoding an anti-apoptotic gene, the bcl-x(L) with a nano-carrier, polymeric micelles (PM) via eye drop to cornea after epithelial debridement, the mRNA level of bcl-x(L) was significantly increased (2.2-fold, P
doi_str_mv 10.1016/j.jconrel.2010.06.006
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A model of epithelial injury by epithelial debridement is established, and keratocyte apoptosis is evidenced by DNA fragmentation and cellular morphological changes in the anterior stroma underlying the injured epithelium. Delivery of plasmid (pCMV-bcl-x(L)-eGFP) encoding an anti-apoptotic gene, the bcl-x(L) with a nano-carrier, polymeric micelles (PM) via eye drop to cornea after epithelial debridement, the mRNA level of bcl-x(L) was significantly increased (2.2-fold, P&lt;0.05) at 48 h and the eGFP mRNA was detected (4571.7 ± 1194.5 copies/μg total RNA). The bcl-x(L)-eGFP fusion protein was also detected in wounded cornea at 48 h after delivery, accompanying with decreased DNA fragmentation and lower caspase-3 activity (P&lt;0.05). In conclusion, eye drop of pCMV-bcl-x(L)-eGFP/PM reduced corneal apoptosis following epithelial debridement.</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2010.06.006</identifier><identifier>PMID: 20600407</identifier><identifier>CODEN: JCREEC</identifier><language>eng</language><publisher>Kidlington: Elsevier</publisher><subject>Animals ; Apoptosis ; bcl-X Protein - biosynthesis ; bcl-X Protein - genetics ; Biological and medical sciences ; Corneal Diseases - therapy ; Cytomegalovirus - genetics ; Drug Carriers - chemistry ; Epithelium, Corneal - injuries ; Epithelium, Corneal - metabolism ; Epithelium, Corneal - pathology ; Gene Transfer Techniques ; General pharmacology ; Genetic Vectors - chemistry ; Green Fluorescent Proteins - genetics ; In Situ Nick-End Labeling ; Male ; Medical sciences ; Mice ; Mice, Nude ; Micelles ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; Ophthalmic Solutions ; Pharmaceutical technology. 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In conclusion, eye drop of pCMV-bcl-x(L)-eGFP/PM reduced corneal apoptosis following epithelial debridement.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>bcl-X Protein - biosynthesis</subject><subject>bcl-X Protein - genetics</subject><subject>Biological and medical sciences</subject><subject>Corneal Diseases - therapy</subject><subject>Cytomegalovirus - genetics</subject><subject>Drug Carriers - chemistry</subject><subject>Epithelium, Corneal - injuries</subject><subject>Epithelium, Corneal - metabolism</subject><subject>Epithelium, Corneal - pathology</subject><subject>Gene Transfer Techniques</subject><subject>General pharmacology</subject><subject>Genetic Vectors - chemistry</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>In Situ Nick-End Labeling</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Micelles</subject><subject>Microscopy, Electron, Transmission</subject><subject>Microscopy, Fluorescence</subject><subject>Ophthalmic Solutions</subject><subject>Pharmaceutical technology. 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Pharmaceutical industry</topic><topic>Pharmacology. 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A model of epithelial injury by epithelial debridement is established, and keratocyte apoptosis is evidenced by DNA fragmentation and cellular morphological changes in the anterior stroma underlying the injured epithelium. Delivery of plasmid (pCMV-bcl-x(L)-eGFP) encoding an anti-apoptotic gene, the bcl-x(L) with a nano-carrier, polymeric micelles (PM) via eye drop to cornea after epithelial debridement, the mRNA level of bcl-x(L) was significantly increased (2.2-fold, P&lt;0.05) at 48 h and the eGFP mRNA was detected (4571.7 ± 1194.5 copies/μg total RNA). The bcl-x(L)-eGFP fusion protein was also detected in wounded cornea at 48 h after delivery, accompanying with decreased DNA fragmentation and lower caspase-3 activity (P&lt;0.05). 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subjects Animals
Apoptosis
bcl-X Protein - biosynthesis
bcl-X Protein - genetics
Biological and medical sciences
Corneal Diseases - therapy
Cytomegalovirus - genetics
Drug Carriers - chemistry
Epithelium, Corneal - injuries
Epithelium, Corneal - metabolism
Epithelium, Corneal - pathology
Gene Transfer Techniques
General pharmacology
Genetic Vectors - chemistry
Green Fluorescent Proteins - genetics
In Situ Nick-End Labeling
Male
Medical sciences
Mice
Mice, Nude
Micelles
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Ophthalmic Solutions
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Plasmids
Polyethylene Glycols - chemistry
Promoter Regions, Genetic
Propylene Glycols - chemistry
Recombinant Fusion Proteins - biosynthesis
Recombinant Fusion Proteins - genetics
title Polymeric micelle gene delivery of bcl-XL via eye drop reduced corneal apoptosis following epithelial debridement
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