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Updated: May 3, 2026
Retinal Detachment Model in Rodents by Subretinal Injection of Sodium Hyaluronate
Published on: September 11, 2013
Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 expression in murine experimental retinal detachment
Bongsu Kim1, Mohamed H Abdel-Rahman, Tiffany Wang
1Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States.
Purpose:
Matrix metalloproteinases (MMPs) and their inhibitors play a role in the pathobiology of retinal detachment (RD) and proliferative vitreoretinopathy (PVR). Proliferative vitreoretinopathy is facilitated by chronic retinal detachment and involves excessive deposition of extracellular matrix (ECM) proteins. Matrix metalloproteinase-2 and -13 are important modulators of the ECM which have not been evaluated in RD. The purpose of this study was to investigate the retinal expression of select MMPs, including MMP-12, MMP-13, and associated inhibitors in a murine model of retinal detachment.
Methods:
Transient or chronic retinal detachments (RDs) were induced by subretinal injection of either saline (SA) or hyaluronic acid (HA) in C57BL/6 mice. To confirm that the HA-RD model has features consistent with PVR-like changes, glial activation and subretinal fibrosis were evaluated with immunofluorescence, dilated fundus examination, and spectral-domain optical coherence tomography (SD-OCT). Gene expression was quantified by qRT-PCR. Proteins were assayed by immunoblot and immunohistochemistry.
Results:
Hyaluronic acid RD eyes developed gliosis and subretinal fibrosis on dilated exam, SD-OCT, and immunofluorescence analysis. Gene expression of Mmp-12 and Mmp-13, and Timp-1 was strongly upregulated at all time points in RD compared with controls. Timp-2, Mmp-2, and Mmp-9 expression was modest. Hyaluronic acid RDs exhibited more MMP and TIMP expression than SA-RDs. MMP-12, -13, and TIMP-1 proteins were elevated in RDs compared with controls. Immunohistochemistry revealed moderate to strong MMP-13 levels in subretinal space macrophages.
Conclusions:
Fibrosis can develop in the HA-RD model. There is an upregulation of select MMPs that may modulate the wound healing process following RD.
Insights
Matrix metalloproteinases (MMPs) and their inhibitors are upregulated following retinal detachment (RD). This study investigated MMP-12, MMP-13, and TIMP-1 in a murine RD model, revealing their potential role in modulating wound healing.
Area of Science:
- Ophthalmology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) and their inhibitors are crucial in extracellular matrix (ECM) remodeling.
- Proliferative vitreoretinopathy (PVR), a severe complication of retinal detachment (RD), involves excessive ECM deposition.
- The role of specific MMPs, such as MMP-12 and MMP-13, in RD pathogenesis remains underexplored.
Purpose of the Study:
- To investigate the retinal expression of matrix metalloproteinases (MMPs) -12, -13, and associated inhibitors in a murine model of retinal detachment (RD).
- To evaluate the potential role of these MMPs in the pathobiology of RD and PVR-like changes.
Main Methods:
- Retinal detachment (RD) was induced in C57BL/6 mice using subretinal injections of saline or hyaluronic acid (HA).
- PVR-like changes, including glial activation and subretinal fibrosis, were assessed using immunofluorescence and SD-OCT.
- Gene expression (qRT-PCR) and protein levels (immunoblot, immunohistochemistry) of MMPs and tissue inhibitors of metalloproteinases (TIMPs) were quantified.
Main Results:
- Hyaluronic acid-induced RDs exhibited significant gliosis and subretinal fibrosis.
- Gene expression of MMP-12, MMP-13, and TIMP-1 was markedly upregulated in RD eyes compared to controls.
- Elevated protein levels of MMP-12, MMP-13, and TIMP-1 were observed, with MMP-13 localized to macrophages in the subretinal space.
Conclusions:
- The hyaluronic acid-induced RD model demonstrates features consistent with PVR, including fibrosis.
- Upregulation of specific MMPs, particularly MMP-12 and MMP-13, suggests their involvement in the wound healing response following retinal detachment.
