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Delivery of ciliary neurotrophic factor via lentiviral-mediated transfer protects axotomized retinal ganglion cells for an extended period of time.

Abstract
Ciliary neurotrophic factor (CNTF) has recently been demonstrated to be one of the most promising neurotrophic factors to improve both the survival and regeneration of injured retinal ganglion cells (RGCs). In the present study, we used optic nerve transection as an in vivo model to evaluate the effectiveness of a self-inactivating, replication-deficient lentiviral-mediated transfer of human ciliary neurotrophic factor (SIN-PGK-CNTF) on the survival of axotomized adult rat RGCs. Counts of dextran-fluorescein isothiocyanate conjugated (D-FITC)-retrogradely labeled RGCs revealed that the percentage of RGCs was drastically reduced (<90% cell death) 21 days after optic nerve transection. Retinal sections stained with X-gal revealed that intravitreal injection of the control LacZ-expressing lentiviral vector (LV-LacZ) resulted in the transduction of RGCs and retinal pigment epithelium (RPE) cells. A single intravitreal injection of LV-CNTF at the time of axotomy significantly enhanced RGC survival at 14 and 21 days postaxotomy compared to controls. These results demonstrate for the first time that rapid and prolonged delivery of CNTF using lentiviral-mediated gene transfer to the retina is an effective treatment for rescuing axotomized RGCs for an extended period of time. These results suggest that early and continuous administration of CNTF could serve as a potential treatment for retinal disorders involving optic neuropathy and RGC injury such as in glaucoma.
AuthorsBrian A van Adel, Corinne Kostic, Nicole Déglon, Alexander K Ball, Yvan Arsenijevic
JournalHuman gene therapy (Hum Gene Ther) Vol. 14 Issue 2 Pg. 103-15 (Jan 20 2003) ISSN: 1043-0342 [Print] United States
PMID12614562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Ciliary Neurotrophic Factor
Topics
  • Animals
  • Axotomy
  • Cell Survival
  • Ciliary Neurotrophic Factor (genetics, metabolism)
  • Female
  • Gene Transfer Techniques
  • Genes, Reporter
  • Genetic Vectors
  • Lentivirus
  • Microscopy, Confocal
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells (metabolism)
  • Time Factors

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