Regulation of corneal repair by particle-mediated gene transfer of opioid growth factor receptor complementary DNA

Research output: Contribution to journalArticle

25 Citations (Scopus)

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,DNAsynthesis (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.

Original languageEnglish (US)
Pages (from-to)1620-1624
Number of pages5
JournalArchives of Ophthalmology
Volume124
Issue number11
DOIs
StatePublished - Nov 1 2006

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Complementary DNA
Genes
Cornea
Bromodeoxyuridine
Corneal Diseases
Keratitis
Photography
DNA
Firearms
methionine-enkephalin receptor
Fluorescein
Genetic Therapy
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
Plasmids

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

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title = "Regulation of corneal repair by particle-mediated gene transfer of opioid growth factor receptor complementary DNA",
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,DNAsynthesis (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.",
author = "Ian Zagon and Joseph Sassani and Malefyt, {Kristin J.} and Patricia McLaughlin",
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Regulation of corneal repair by particle-mediated gene transfer of opioid growth factor receptor complementary DNA. / Zagon, Ian; Sassani, Joseph; Malefyt, Kristin J.; McLaughlin, Patricia.

In: Archives of Ophthalmology, Vol. 124, No. 11, 01.11.2006, p. 1620-1624.

Research output: Contribution to journalArticle

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T1 - Regulation of corneal repair by particle-mediated gene transfer of opioid growth factor receptor complementary DNA

AU - Zagon, Ian

AU - Sassani, Joseph

AU - Malefyt, Kristin J.

AU - McLaughlin, Patricia

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N2 - 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,DNAsynthesis (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.

AB - 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,DNAsynthesis (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.

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