Open AccessCell‐penetrating peptide TAT‐mediated delivery of acidic FGF to retina and protection against ischemia–reperfusion injury in rats
Author(s) -
Wang Yi,
Lin Haihuan,
Lin Shaoqiang,
Qu Jia,
Xiao Jian,
Huang Yadong,
Xiao Yechen,
Fu Xiaobing,
Yang Yongguang,
Li Xiaokun
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00786.x
Subject(s) - retina , ganglion cell layer , retinal , reperfusion injury , apoptosis , biology , microbiology and biotechnology , outer nuclear layer , inner nuclear layer , ischemia , medicine , biochemistry , neuroscience
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.