Prolonged protective effect of basic fibroblast growth factor-impregnated nanoparticles in royal college of surgeons rats.
OBJECTIVE
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.
Sakai
Tsutomu
T
Department of Ophthalmology, Jikei University School of Medicine, Nishishinbashi, Tokyo, Japan. tstmski@jikei.ac.jp
Kuno
Noriyuki
N
Takamatsu
Fumihiko
F
Kimura
Erika
E
Kohno
Hideo
H
Okano
Kiichiro
K
Kitahara
Kenji
K
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D004195:Disease Models, Animal; D004337:Drug Carriers; D004596:Electroretinography; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000378:metabolism; D005780:Gelatin; D020287:In Situ Nick-End Labeling; D007267:Injections; D018613:Microscopy, Confocal; D053758:Nanoparticles; D051381:Rats; D011922:Rats, Mutant Strains; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012235:Rhodamines / Q000378:metabolism; D014822:Vitreous Body
D004337:Drug Carriers; D012235:Rhodamines; D016222:Fibroblast Growth Factor 2; D005780:Gelatin