IOVS Journal of Neuroscience
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(Investigative Ophthalmology and Visual Science. 2007;48:3381-3387.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1242
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Prolonged Protective Effect of Basic Fibroblast Growth Factor–Impregnated Nanoparticles in Royal College of Surgeons Rats

Tsutomu Sakai,1 Noriyuki Kuno,2 Fumihiko Takamatsu,2 Erika Kimura,2 Hideo Kohno,1 Kiichiro Okano,1 and Kenji Kitahara1

1From the Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; and the 2Research and Development Center, Santen Pharmaceutical Co., Ltd., Nara, Japan.

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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Copyright © 2007 by the Association for Research in Vision and Ophthalmology