Regulation of connexin43 gap junction protein triggers vascular recovery and healing in human ocular persistent epithelial defect wounds.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 0211301 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1424 (Electronic) Linking ISSN: 00222631 NLM ISO Abbreviation: J Membr Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, Springer.
    • Subject Terms:
      Connexin 43/*metabolism ; Connexins/*metabolism ; Corneal Diseases/*drug therapy ; Epithelium, Corneal/*drug effects ; Epithelium, Corneal/*metabolism ; Oligodeoxyribonucleotides, Antisense/*therapeutic use; Adult ; Connexin 43/antagonists & inhibitors ; Connexins/antagonists & inhibitors ; Corneal Diseases/metabolism ; Epithelium, Corneal/pathology ; Humans ; Male ; Middle Aged ; Wound Healing/drug effects
    • Abstract:
      Transiently blocking the expression of the gap junction protein connexin43 using antisense oligodeoxynucleotides or blocking hemichannels with connexin mimetic peptides has been shown to significantly improve outcomes in a range of acute wound models. Less is known about their likely effects in nonhealing wounds. In the eye, prolonged inflammation and lack of epithelial recovery in nonhealing corneal epithelial wounds may lead to corneal opacity, blindness or enucleation. We report here the first human applications of antisense oligodeoxynucleotides that transiently block translation of connexin43 in a prospective study of five eyes with severe ocular surface burns (persistent epithelial defects), which were unresponsive to established therapy for 7 days to 8 weeks prior to treatment. Connexin43-specific antisense oligodeoxynucleotide was delivered in cold, thermoreversible Poloxamer407 gel under either an amniotic membrane graft or a bandage contact lens. The connexin43-specific antisense application reduced inflammation within 1-2 days, and in all five eyes complete and stable corneal reepithelialization was obtained. Recovery of the vascular bed and limbal reperfusion appeared to precede corneal epithelial recovery. We conclude that connexin modulation provides a number of benefits for nonhealing ocular burn wounds, one of which is to promote vascular recovery.
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    • Accession Number:
      0 (Connexin 43)
      0 (Connexins)
      0 (Oligodeoxyribonucleotides, Antisense)
    • Publication Date:
      Date Created: 20120717 Date Completed: 20121204 Latest Revision: 20211021
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/s00232-012-9460-4
    • Accession Number:
      22797940