Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 14, Issue 7, Pages 1998-2005Publisher
WILEY
DOI: 10.1111/j.1582-4934.2009.00786.x
Keywords
cell-penetrating peptide; fibroblast growth factor; ischemia and reperfusion injury; retina; transactivator of transcription peptide
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Funding
- Zhejiang Province Extremely Key Subject Building
- Zhejiang province key Natural Science Foundation [Z205755]
- National Natural Scientific Foundation of China [30670541]
- New Century Excellent Talents in University
- Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
- National Basic Research Program of China [2005CB522603]
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The development of non-invasive ocular drug delivery systems is of practical importance in the treatment of retinal disease. In this study, we evaluated the efficacy of transactivator of transcription protein transduction domain (TAT-PTD, TAT(49-57)) as a vehicle to deliver acidic FGF (aFGF) to retina in rats. TAT-conjugated aFGF-His (TAT-aFGF-His) exhibited efficient penetration into the retina following topical administration to the ocular surface. Immunochemical staining with anti-His revealed that TAT-aFGF-His proteins were readily found in the retina (mainly in the ganglion cell layer) at 30 min. and remained detectable for at least 8 hrs after administration. In contrast, His+ proteins were undetectable in the retina after topical administration of aFGF-His, indicating that aFGF-His cannot penetrate the ocular barrier. Furthermore, TAT-aFGF-His, but not aFGF-His, mediated significant protection against retinal ischemia-reperfusion (IR) injury. After IR injury, retina from TAT-aFGF-His-treated rats showed better-maintained inner retinal layer structure, reduced apoptosis of retinal ganglion cells and improved retinal function compared to those treated with aFGF-His or PBS. These results indicate that conjugation of TAT to aFGF-His can markedly improve the ability of aFGF-His to penetrate the ocular barrier without impairing its biological function. Thus, TAT(49-57) provides a potential vehicle for efficient drug delivery in the treatment of retinal disease.
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