Activation of AP-1 and increased synthesis of MMP-9 in the rabbit retina induced by lipid hydroperoxide.
OBJECTIVE
We identified the temporal expression of activator protein-1 (AP-1) and matrix metalloproteinases (MMPs) after linoleic acid hydroperoxide (LHP) induction of retinal neovascularization.


METHODS
After injection of LHP into the vitreous of rabbits, samples were collected for AP-1 binding activity and mRNA for MMP-9 and MMPs activity. AP-1 binding activity was measured by electrophoretic mobility shift assay. MMP-9 activity was measured by zymography and mRNA by quantitative RT-PCR.


RESULTS
AP-1 binding activity was increased at 1-3 hr. MMP-9 mRNA levels were increased at 3 hr in the neural retina and by 12 hr in the retinal pigment epithelium (RPE) layer. MMP-9 proteolytic activity was elevated within the neural retina and within the vitreous and in the RPE-interphotoreceptor matrix (IPM) at 12 hr and peaked at 24 hr or 4 days.


CONCLUSIONS
LHP increases the transcription factor AP-1 which in turn may regulate retinal MMP-9 synthesis during neovascularization.
Iwai
Shinichi
S
Departement of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Florida, USA. shinichi@med.showa-u.ac.jp
Aljada
Ahmad
A
Higa
Akira
A
Nakanishi-Ueda
Takako
T
Fukuda
Shohei
S
Kamegawa
Maki
M
Iwabuchi
Shigehiro
S
Ueda
Toshihiko
T
Caballero
Sergio
S
Browne
Richard
R
Afzal
Aqeela
A
Grant
Maria
M
Yasuhara
Hajime
H
Koide
Ryohei
R
Oguchi
Katsuji
K
Dandona
Paresh
P
Armstrong
Donald
D
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D024202:Electrophoretic Mobility Shift Assay; D007267:Injections; D008041:Linoleic Acids / Q000633:toxicity*; D008054:Lipid Peroxides / Q000633:toxicity*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D015861:Retinal Neovascularization / Q000139:chemically induced* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014822:Vitreous Body
D008041:Linoleic Acids; D008054:Lipid Peroxides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D020780:Matrix Metalloproteinase 9