Wang, YiLin, HaihuanLin, ShaoqiangQu, JiaXiao, JianHuang, YadongXiao, YechenFu, XiaobingYang, YongguangLi, Xiaokun2015-05-042009Wang, Yi, Haihuan Lin, Shaoqiang Lin, Jia Qu, Jian Xiao, Yadong Huang, Yechen Xiao, Xiaobing Fu, Yongguang Yang, and Xiaokun Li. 2009. “Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia–reperfusion injury in rats.” Journal of Cellular and Molecular Medicine 14 (7): 1998-2005. doi:10.1111/j.1582-4934.2009.00786.x. http://dx.doi.org/10.1111/j.1582-4934.2009.00786.x.1582-1838http://nrs.harvard.edu/urn-3:HUL.InstRepos:15034964Abstract 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, TAT49–57) 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, TAT49–57 provides a potential vehicle for efficient drug delivery in the treatment of retinal disease.en-UScell-penetrating peptidefibroblast growth factorischemia and reperfusion injuryretinatransactivator of transcription peptideJournal Article2015-05-0410.1111/j.1582-4934.2009.00786.x