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Tsutomu Sakai, Noriyuki Kuno, Fumihiko Takamatsu, Erika Kimura, Hideo Kohno, Kiichiro Okano, Kenji Kitahara; Prolonged Protective Effect of Basic Fibroblast Growth Factor–Impregnated Nanoparticles in Royal College of Surgeons Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(7):3381-3387. doi: 10.1167/iovs.06-1242.
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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 μg), or bFGF-NPs (2.5 μg). 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.
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