Abstract
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