Regulation of corneal repair by particle-mediated gene transfer of opioid growth factor receptor complementary DNA. Journal   Archives of ophthalmology. Citation   Arch Ophthalmol. 124(11):1620-4 Publication date   2006 Nov Authors   Zagon IS Sassani JW Malefyt KJ McLaughlin PJ Investigators   Patricia J. McLaughlin Joseph W. Sassani Ian S. Zagon Grant agencies   National Eye Institute Grants   NEI EY13734 MeSH headings   Cornea DNA, Complementary Eye Injuries Gene Therapy Receptors, Opioid Wound Healing Wounds, Nonpenetrating MeSH qualifiers   injuries genetics therapy Abstract   OBJECTIVE: To determine whether molecular manipulation of the opioid growth factor receptor (OGFr) alters corneal reepithelialization following central corneal abrasion in rats. METHODS: The plasmid pcDNA3.1 + OGFr, carrying the rat OGFr complementary DNA in both the sense and antisense orientations, and empty vector (EV), were delivered by gene gun to the rat cornea. After 24 hours, corneas were abraded and reepithelialization was documented by fluorescein photography. Twenty-four hours after wounding, DNA synthesis (with bromodeoxyuridine) was examined. RESULTS: Eyes transfected with sense constructs of OGFr had corneal defects that were 24%, 52%, and 50% larger than the EV group at 16, 24, and 28 hours, respectively. Conversely, corneas transfected with antisense constructs of OGFr had corneal defects that were 56% and 48% smaller than the EV group at 16 and 24 hours, respectively. Bromodeoxyuridine labeling in the basal and suprabasal layers of the antisense group were increased 3.3- and 3.7-fold, respectively, in DNA synthesis from corresponding EV layers; DNA synthesis was comparable in the sense and EV groups. CONCLUSIONS: Excess OGFr delays reepithelialization, whereas attenuation of OGFr accelerates repair of the corneal surface. Clinical Relevance Inhibition of opioid growth factor action using gene therapy could be important in the treatment of corneal diseases such as nonhealing and recurrent erosions, diabetic keratopathy, and neurotrophic keratitis.