Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 Expression in Murine Experimental Retinal Detachment

Kim, Bongsu; Abdel‐Rahman, Mohamed H.; Wang, Tiffany; Pouly, Severin; Mahmoud, Ashraf M.; Cebulla, Colleen M.

doi:10.1167/iovs.13-13374

Cited by 23 publications

(29 citation statements)

References 45 publications

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“…After WTC dust exposure, we also found that MMP-12 increased in the lung 7 d post-exposure. However, as MMP-12 promotes both inflammation and wound repair, its role in WTC dust-induced lung injury and disease pathogenesis is unclear (Nenan et al, 2005; Iwanami et al, 2009; Kim et al, 2014). Findings that the risk of developing WTC dust induced lung disease is reduced in exposed individuals with elevated serum levels of MMP-12 suggest that it may be protective (Kwon et al, 2013); however, this remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung

Sunil

Vayas

Fang

et al. 2017

Experimental and Molecular Pathology

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Exposure to World Trade Center (WTC) dust has been linked to respiratory disease in humans. In the present studies we developed a rodent model of WTC dust exposure to analyze lung oxidative stress and inflammation, with the goal of elucidating potential epigenetic mechanisms underlying these responses. Exposure of mice to WTC dust (20 μg, i.t.) was associated with upregulation of heme oxygenase-1 and cyclooxygenase-2 within 3 days, a response which persisted for at least 21 days. Whereas matrix metalloproteinase was upregulated 7 days post-WTC dust exposure, IL-6RA1 was increased at 21 days; conversely, expression of mannose receptor, a scavenger receptor important in particle clearance, decreased. After WTC dust exposure, increases in methylation of histone H3 lysine K4 at 3 days, lysine K27 at 7 days and lysine K36, were observed in the lung, along with hypermethylation of Line-1 element at 21 days. Alterations in pulmonary mechanics were also observed following WTC dust exposure. Thus, 3 days post-exposure, lung resistance and tissue damping were decreased. In contrast at 21 days, lung resistance, central airway resistance, tissue damping and tissue elastance were increased. These data demonstrate that WTC dust-induced inflammation and oxidative stress are associated with epigenetic modifications in the lung and altered pulmonary mechanics. These changes may contribute to the development of WTC dust pathologies.

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Section: Discussionmentioning

confidence: 99%

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung

Sunil

Vayas

Fang

et al. 2017

Experimental and Molecular Pathology

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“…In animal PVR models, gas compression and vitrectomy are 2 main methods to disturb the vitreous, usually before intravitreal injection or other surgical manipulations [49, 65-68]. A direct way to mimic advanced PVR is the development of chronic RD simply by subretinal injection [69, 70]. This model develops some features of PVR, including activation of the Müller glia and extension of glial processes below the external limiting membrane [69].…”

Section: Design Of Pvr Animal Models For Pharmaceutical Investigationmentioning

confidence: 99%

“…A direct way to mimic advanced PVR is the development of chronic RD simply by subretinal injection [69, 70]. This model develops some features of PVR, including activation of the Müller glia and extension of glial processes below the external limiting membrane [69]. …”

Section: Design Of Pvr Animal Models For Pharmaceutical Investigationmentioning

confidence: 99%

“…Different combinations of cells or factors also can be injected along with these surgical manipulations to stimulate PVR. Recently, a chronic RD murine model was developed by subretinal injection to mimic the advanced stage of PVR [69, 70]. One thing should be kept in mind when artificial trauma is involved in model establishment: the PVR that occurs after penetrating trauma differs from PVR following RD surgery in many aspects.…”

Section: Application Of Pvr Models For Pharmaceutical Investigationmentioning

confidence: 99%

“…Compared to other cell types, PVR development with the macrophage injection model seems slower. The chronic RD model, in contrast, bypasses all early pathologic steps [69, 70]. Thus, use of this model in drug screening is rare.…”

Section: Limitation Of Current Animal Models Research Needs and Futmentioning

confidence: 99%

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Animal Models of Proliferative Vitreoretinopathy and Their Use in Pharmaceutical Investigations

2018

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Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system

Lemmens

Bollaerts

Bhumika

et al. 2015

J of Comparative Neurology

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Overcoming the failure of axon regeneration in the mammalian central nervous system (CNS) after injury remains a major challenge, which makes the search for proregenerative molecules essential. Matrix metalloproteinases (MMPs) have been implicated in axonal outgrowth during CNS development and show increased expression levels during vertebrate CNS repair. In mammals, MMPs are believed to alter the suppressive extracellular matrix to become more permissive for axon regrowth. We investigated the role of MMPs in axonal regeneration following optic nerve crush (ONC) in adult zebrafish, which fully recover from such injuries due to a high intrinsic axon growth capacity and a less inhibitory environment. Lowering general retinal MMP activity through intravitreal injections of GM6001 after ONC strongly reduced retinal ganglion cell (RGC) axonal regrowth, without influencing RGC survival. Based on a recently performed transcriptome profiling study, the expression pattern of four MMPs after ONC was determined via combined use of western blotting and immunostainings. Mmp-2 and -13a were increasingly present in RGC somata during axonal regrowth. Moreover, Mmp-2 and -9 became upregulated in regrowing RGC axons and inner plexiform layer (IPL) synapses, respectively. In contrast, after an initial rise in IPL neurites and RGC axons during the injury response, Mmp-14 expression decreased during regeneration. Altogether, a phase-dependent expression pattern for each specific MMP was observed, implicating them in axonal regrowth and inner retina remodeling after injury. In conclusion, these data suggest a novel, neuron-intrinsic function for multiple MMPs in axon regrowth that is distinct from breaking down environmental barriers. J. Comp. Neurol. 524:1472-1493, 2016. © 2015 Wiley Periodicals, Inc.

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Retinal MMP-12, MMP-13, TIMP-1, and TIMP-2 Expression in Murine Experimental Retinal Detachment

Abstract: Fibrosis can develop in the HA-RD model. There is an upregulation of select MMPs that may modulate the wound healing process following RD.

Cited by 23 publications

References 45 publications

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung

World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung

Animal Models of Proliferative Vitreoretinopathy and Their Use in Pharmaceutical Investigations

Matrix metalloproteinases as promising regulators of axonal regrowth in the injured adult zebrafish retinotectal system

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