Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia-reperfusion injury in rats.
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.
Key Laboratory of Biotechnology Pharmaceutical Engineering of Zhejiang Province, School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou, PR China.
Yi
Y
Wang
Haihuan
H
Lin
Shaoqiang
S
Lin
Jia
J
Qu
Jian
J
Xiao
Yadong
Y
Huang
Yechen
Y
Xiao
Xiaobing
X
Fu
Yongguang
Y
Yang
Xiaokun
X
Li
D000818:Animals; D005346:Fibroblast Growth Factors / Q000008:administration & dosage*; D015696:Gene Products, tat / Q000008:administration & dosage*; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D012160:Retina / Q000378:metabolism*
D015696:Gene Products, tat; D005346:Fibroblast Growth Factors