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 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<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<0.05). In conclusion, eye drop of pCMV-bcl-x(L)-eGFP/PM reduced corneal apoptosis following epithelial debridement.
Tong
Yaw-Chong
YC
College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Chang
Shwu-Fen
SF
Kao
Winston W-Y
WW
Liu
Chia-Yang
CY
Liaw
Jiahorng
J
D000818:Animals; D017209:Apoptosis; D003316:Corneal Diseases / Q000628:therapy; D003587:Cytomegalovirus / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D019573:Epithelium, Corneal / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009883:Ophthalmic Solutions; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D011409:Propylene Glycols / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics*; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics*
C494812:Bcl2l1 protein, mouse; D004337:Drug Carriers; D008823:Micelles; D009883:Ophthalmic Solutions; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols