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.
Wang
Yi
Y
Key Laboratory of Biotechnology Pharmaceutical Engineering of Zhejiang Province, School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou, PR China.
Lin
Haihuan
H
Lin
Shaoqiang
S
Qu
Jia
J
Xiao
Jian
J
Huang
Yadong
Y
Xiao
Yechen
Y
Fu
Xiaobing
X
Yang
Yongguang
Y
Li
Xiaokun
X
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