Abstract
Purpose: :
To evaluate C-type natriuretic peptide (CNP) gene expression delivered via ultrasound-microbubble mediated gene transfection and its effects on rabbit and monkey intraocular pressure (IOP).
Methods: :
Mixture (80 µl), containing plasmids (150 ng/µl) encoding CNP or copGFP dissolved in SonoVue® microbubble, was injected into the anterior chamberof New Zealand white rabbits or Tibetan monkeys after equal volume of aqueous humor was drawn. The limbus corneae was then exposed to ultrasound for 1 min (Frequency = 1 MHz, Intensity = 1 W/cm2, Duty Cycle = 20%) . IOP was monitored daily for 2 weeks by the TonoLab rebound tonometer. Frozen sections for rabbit limbus corneaes were prepared to confirm gene expression.
Results: :
CNP gene transfer significantly (P<0.05) lowered rabbit and monkey IOP starting 48 h after treatment. In rabbits, the maximum reduction (1.85±0.51 mm Hg) was shown on day 5. In monkeys, the maximum reduction (3.17±0.95 mm Hg) was observed on day 3. The rabbit IOP change correlated with gene expression at the angle of anterior chamber, as well as the vicinal cornea and sclera.
Conclusions: :
Ultrasound-microbubble mediated transfection of CNP gene lowered IOP and may be a safe and effective means for glaucoma gene therapy.
Keywords: gene transfer/gene therapy • intraocular pressure