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(Investigative Ophthalmology and Visual Science. 2001;42:210-215.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

The Balance between Proteinases and Inhibitors in a Murine Model of Proliferative Retinopathy

Susan Majka1, Paul McGuire1,2, Sage Colombo1 and Arup Das1,3

1 From the Department of Surgery, Division of Ophthalmology, and the 2 Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque; and the 3 Division of Ophthalmology, Veterans Administration Medical Center, Albuquerque, New Mexico.

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 undetectable.

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 stimulation.




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