Retina protective effect of acidic fibroblast growth factor after canceling its mitogenic activity.
OBJECTIVE
The aim of this study was to investigate the effect of mutant of acidic fibroblast growth factor (MaFGF) on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in Sprague-Dawley rats.


METHODS
Fifty (50)-day-old female Sprague-Dawley rats were given a single intraperitoneal injection of normal saline (NS) or 60 mg x kg(-1) body weight of MNU, and then NS or different doses of MaFGF were injected intravitreally twice at 0 and 12 h after NS or MNU treatment. After NS or MNU treatment for different times, the apoptotic index of the photoreceptor cell was detected by TUNEL labeling, whereas the mRNA expressions and the protein levels of antiapoptotic Bcl-2 and proapoptotic Bax were determined by reverse transcriptase polymerase chain reaction and Western blotting, respectively. Retinal damage was evaluated based on retinal thickness.


RESULTS
MNU-induced retinal damage was partially protected by MaFGF in a dose-independent manner in rats. MaFGF at doses of 1.25 and 2.5 microg could partially suppress photoreceptor cell loss, whereas MaFGF at a dose of 5.0 mug had no protective effect on photoreceptor cell. The apoptotic index at 24 h post-MNU in the peripheral retina was 38.1 +/- 3.6%, whereas 1.25 and 2.5 mug MaFGF markedly reduced it to 27.5 +/- 2.0 and 21.1 +/- 1.9% (P = <0.001), respectively. As compared with the MNU-treated group, MaFGF significantly upregulated the expression of Bcl-2 mRNA and protein and downregulated the expression of Bax mRNA and protein (P = <0.001).


CONCLUSIONS
MaFGF could counteract MNU-induced retinal damage and may be a therapeutic agent for the treatment of retinal degeneration.
Xu
Hua
H
Pharmacy College, Jinan University, Guangzhou, China. huax-mail@163.com
Yang
Jin-Nan
JN
Li
Xiao-Kun
XK
Zheng
Qing
Q
Zhao
Wen
W
Su
Zhi-Jian
ZJ
Huang
Ya-Dong
YD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000494:pharmacology*; D008770:Methylnitrosourea; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016220:Fibroblast Growth Factor 1; D008770:Methylnitrosourea