April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Iontophoretic Delivery of an Anti-Connective Tissue Growth Factor Antisense Oligonucleotide Into the Cornea Following Excimer Ablation Reduced Corneal Haze
Author Affiliations & Notes
  • D. J. Gibson
    Biochemistry and Molecular Biology,
    University of Florida, Gainesville, Florida
  • S. S. Tuli
    University of Florida, Gainesville, Florida
  • G. S. Schultz
    University of Florida, Gainesville, Florida
  • Footnotes
    Commercial Relationships  D.J. Gibson, US 61/175,331, P; S.S. Tuli, US 61/175,331, P; G.S. Schultz, US 61/175,331, P.
  • Footnotes
    Support  NIH Grant EY05587 and an NEI T32 Grant
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 398. doi:
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      D. J. Gibson, S. S. Tuli, G. S. Schultz; Iontophoretic Delivery of an Anti-Connective Tissue Growth Factor Antisense Oligonucleotide Into the Cornea Following Excimer Ablation Reduced Corneal Haze. Invest. Ophthalmol. Vis. Sci. 2010;51(13):398.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To test the anti-fibrotic effects of an iontophoretically delivered anti-Connective Tissue Growth Factor (CTGF) antisense oligonucleotide (ASO) following excimer ablation.

Methods: : Five rabbits were anesthetized with isoflurane:oxygen and corneas were treated with tetracaine eye drops. A 6 mm diameter central wound was created in 9 of the 10 eyes using an excimer laser, with one eye reserved as a normal eye standard. The initial and post-wounding corneal thicknesses were measured by ultrasonic pachymetry. Buffered, dual-phase, iontophoresis was performed for 5 min at 4 mA (3 rabbits) or 0 mA (1 rabbit) with either a scrambled or anti-CTGF ASO (2 mg/ml). Following iontophoresis, wound size/location and corneal thickness were measured daily until wounds re-epithelialized by macrophotography of fluorescein staining and by ultrasonic pachymetry. Additional examinations were performed on days 8, 9, & 14 to measure corneal thickness and haze. Briefly, haze was quantified by reflectivity measurements using anti-red light macrophotography.

Results: : Iontophoresis was well tolerated with no signs of inflammation or burns noted in any eyes. All eyes were reepithelialized by day 4 with no difference noted between the rates of epithelial healing for the three treatment groups. Corneal edema was significantly reduced in eyes iontophoresed with ASO to CTGF compared to eyes receiving scrambled ASO on days 2 and 3 (p=0.0383; p=0.0284, respectively). Similarly, there was a strong trend for reduced average levels of quantified corneal haze at day 14 in corneas treated with ASO to CTGF compared to control corneas (n=3, avg. intensity = 53.08 vs. 62.82; p=0.19).

Conclusions: : Iontophoretic delivery of CTGF ASO to rabbit corneas following excimer ablation using an improved buffered, dual phase technique resulted in significantly decreased levels of corneal edema compared to the scrambled ASO and also produced a trend for reduced amount of quantified corneal haze.

Keywords: gene transfer/gene therapy • wound healing • imaging/image analysis: clinical 

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