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Susan Majka, Paul McGuire, Sage Colombo, Arup Das; The Balance between Proteinases and Inhibitors in a Murine Model of Proliferative Retinopathy. Invest. Ophthalmol. Vis. Sci. 2001;42(1):210-215.
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purpose. To examine the expression of matrix metalloproteinases (MMPs) and their
inhibitors during the development of retinal neovascularization (NV) in
a mouse model.
methods. A well-characterized murine model of retinal NV was used to study the
expression of specific MMPs (MMP-2, MMP-9, and MT1-MMP) and tissue
inhibitor of metalloproteinases (TIMPs types 1, 2, and 3). NV of the
retina was induced in mice by exposure to 75% O2 from
postnatal day (P)7 to P12, followed by return to room air from P12 to
P17. Expression of MMP mRNA was analyzed by reverse
transcription–polymerase chain reaction (RT-PCR). In addition, retinal
tissue removed from control (without NV) and experimental animals (with
NV) was analyzed for the expression of TIMP-1, TIMP-2, and TIMP-3 mRNA
and protein using RT-PCR and Western blot analysis.
results. During the angiogenic period from P13 to P17, MMP-2 and -9, and MT1-MMP
message expression increased in experimental retinas compared with
control samples. The TIMP-2 message and protein levels increased
steadily in the retina of control animals until P17. This was in
contrast to that seen in the retinas of the experimental animals in
which TIMP-2 message and protein remained low and significantly less
than in control samples. There were no significant changes in TIMP-3
message levels in retinal tissues, and TIMP-1 message and protein were
conclusions. Correlation was made at the mRNA and protein levels of TIMP expression
compared with that of MMPs in a murine model of retinal NV, which
suggests a temporal role for MMP-2 and -9, MT1-MMP, and TIMP-2 in new
vessel formation in response to hypoxic
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