title: Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 expression in murine experimental retinal detachment.
abstract: OBJECTIVE
  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.
authors: Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University, Columbus, Ohio, United States.
authors: Bongsu
authors: B
authors: Kim
authors: Mohamed H
authors: MH
authors: Abdel-Rahman
authors: Tiffany
authors: T
authors: Wang
authors: Severin
authors: S
authors: Pouly
authors: Ashraf M
authors: AM
authors: Mahmoud
authors: Colleen M
authors: CM
authors: Cebulla
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis / Q000235:genetics*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000201:enzymology / Q000473:pathology; D012163:Retinal Detachment / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics*; D041623:Tomography, Optical Coherence
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D012313:RNA; D053509:Matrix Metalloproteinase 13; D053508:Matrix Metalloproteinase 12
keywords: MMP-12; MMP-13; TIMP-1; TIMP-2; extracellular matrix; matrix metalloproteinase; proliferative vitreoretinopathy; retinal detachment; spectral-domain optical coherence tomography; tissue inhibitor metalloproteinase