Retinal pigment epithelium produces matrix metalloproteinases after laser treatment.
OBJECTIVE
To evaluate production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) after panretinal photocoagulation (PRP) of human retinal pigment epithelium (RPE) explants.


METHODS
Treated explants were subjected to substrate zymography to differentiate MMP-2 from MMP-9 and dot immunoblot analysis to quantify MMP-3 and TIMP activity. Tritiated thymidine uptake by RPE cells was measured to document evidence of cellular division in the laser-treated versus control explants.


RESULTS
We detected MMP-2, MMP-3, and TIMP-1. MMP-2 and MMP-3 secretion increased to twice the control values. TIMP decreased until day 4 and then increased by day 6. Tritiated thymidine uptake increased 2.5-fold until day 6, returning to baseline by day 8.


CONCLUSIONS
PRP disturbs MMP/TIMP balance, inhibiting the initiation and maintenance required for active neovascularization. The efficacy of PRP may be due to changes in the expression pattern of metalloproteinases and inhibitors. This model elucidates the possible contribution of PRP to neovascularization regression by demonstrating the effect of laser on TIMP/MMP balance. The effects of PRP may be much more complex than currently understood and most likely involve more than vascular endothelial growth factor and other ischemia-related factors.
Flaxel
Christina
C
Glaucoma Service, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97239-4197, USA. flaxelc@ohsu.edu
Bradle
John
J
Acott
Ted
T
Samples
John R
JR
D000368:Aged; D015153:Blotting, Western; D002455:Cell Division; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D017075:Laser Coagulation; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D009924:Organ Culture Techniques; D010857:Pigment Epithelium of Eye / Q000201:enzymology* / Q000601:surgery*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases