Prolonged protective effect of basic fibroblast growth factor-impregnated nanoparticles in royal college of surgeons rats

Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3381-7. doi: 10.1167/iovs.06-1242.

Abstract

Purpose: To investigate the protective effect of intravitreal injection of basic fibroblast growth factor-impregnated nanoparticles (bFGF-NPs) against photoreceptor degeneration in Royal College of Surgeons (RCS) rats.

Methods: Three-week-old RCS rats received intravitreal injection of PBS, blank NPs, bFGF (2.5 microg), or bFGF-NPs (2.5 microg). Eyes were assessed by morphologic, immunohistochemical, and physiological analyses for the following 8 weeks. Cell death was examined using the TUNEL assay, and bFGF protein levels in the retina were measured by Western blot analysis. Rhodamine (Rh)-labeled bFGF-NPs were injected intravitreally and visualized by confocal microscopy to determine the localization of the nanoparticles in the retina.

Results: Intravitreally injected Rh-labeled bFGF-NPs were found in the outer nuclear layer 6 and 8 weeks after injection. ERG a- and b-wave amplitudes in bFGF-NP-treated retinas were greater than amplitudes in retinas receiving other treatment. Immunocytochemical analysis showed consistently greater opsin preservation in bFGF-NP-treated retinas, and a significantly higher number of photoreceptors and significantly fewer TUNEL-positive cells were present after bFGF-NP treatment than after bFGF treatment. Western blot analysis showed a significant increase in the bFGF level in bFGF-NP-treated retinas.

Conclusions: The results suggest that intravitreally injected bFGF-NPs prevent photoreceptor degeneration by inhibiting apoptosis in the RCS rat retina because of targeting and sustained release of bFGF. This novel drug delivery system for bFGF may serve as a potential short-term treatment for photoreceptor degeneration in humans.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Death
  • Disease Models, Animal*
  • Drug Carriers*
  • Electroretinography
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Fibroblast Growth Factor 2 / metabolism
  • Gelatin
  • In Situ Nick-End Labeling
  • Injections
  • Microscopy, Confocal
  • Nanoparticles*
  • Rats
  • Rats, Mutant Strains
  • Retina / metabolism
  • Retina / pathology
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Retinal Degeneration / prevention & control*
  • Rhodamines / metabolism
  • Vitreous Body

Substances

  • Drug Carriers
  • Rhodamines
  • Fibroblast Growth Factor 2
  • Gelatin