MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

Hove, Inge Van; Lefevere, Evy; Groef, Lies De; Sergeys, Jurgen; Salinas‐Navarro, Manuel; Libert, Claude; Vandenbroucke, Roosmarijn E.; Moons, Lieve

doi:10.3390/ijms17111825

Cited by 31 publications

(26 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot and immunohistochemical stainings for MMP‐3 confirmed this elevated expression at early time points after ONC (Figure 3b–f). Notably, and in agreement with previous studies in the mouse retina (De Groef, Andries, Lemmens, Van Hove, & Moons, 2015; Hu et al, 2016; Van Hove et al, 2016), MMP‐3 was found to be expressed in the end feet and radial processes of Müller glia/astrocytes, as shown by co‐localization of MMP‐3 and the Müller glia/astrocyte marker glutamine synthetase (GS) (Figure 3c′). Importantly, these astrocytic and Müller glia end foot processes constitute the glia limitans of the retinal NVU.…”

Section: Resultssupporting

confidence: 93%

See 1 more Smart Citation

Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury

Lefevere

Salinas‐Navarro

Andries

et al. 2020

Glia

Self Cite

View full text Add to dashboard Cite

Increasing evidence suggests that functional impairments at the level of the neurovascular unit (NVU) underlie many neurodegenerative and neuroinflammatory diseases. While being part of the NVU, astrocytes have been largely overlooked in this context and only recently, tightening of the glia limitans has been put forward as an important neuroprotective response to limit these injurious processes. In this study, using the retina as a central nervous system (CNS) model organ, we investigated the structure and function of the glia limitans, and reveal that the blood-retina barrier and glia limitans function as a coordinated double barrier to limit infiltration of leukocytes and immune molecules. We provide in vitro and in vivo evidence for a protective response at the NVU upon CNS injury, which evokes inflammation-induced glia limitans tightening. Matrix metalloproteinase-3 (MMP-3) was found to be a crucial regulator of this process, thereby revealing its beneficial and immunomodulatory role in the CNS. in vivo experiments in which MMP-3 activity was deleted via genetic and pharmacological approaches, combined with a comprehensive study of tight junction molecules, glial end feet markers, myeloid cell infiltration, cytokine expression and neurodegeneration, show that MMP-3 attenuates neuroinflammation and neurodegeneration by tightening the glia limitans, thereby pointing to a prominent role of MMP-3 in preserving the integrity of the NVU upon injury. Finally, we gathered promising evidence to suggest that IL1b, which is also regulated by MMP-3, is at least one of the molecular messengers that induces glia limitans tightening in the injured CNS.

show abstract

Section: Resultssupporting

confidence: 93%

“…Adherent leukocytes in the retinal vessels were visualized as previously reported (Van Hove et al, 2016). Briefly, mice were transcardially perfused with saline and heparin (140 mg/L), followed by FITC‐Concanavalin A lectin (FITC‐ConA, 40 μg/ml in PBS 1×, pH 7.5, Vector Labs).…”

Section: Methodsmentioning

confidence: 99%

Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury

Lefevere

Salinas‐Navarro

Andries

et al. 2020

Glia

Self Cite

View full text Add to dashboard Cite

show abstract

“…High quality representative pictures were taken on a confocal microscope (Olympus FV1000; Olympus Corp., Tokyo, Japan). 44…”

Section: Leukostasismentioning

confidence: 99%

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Sergeys

Étienne

Hove

et al. 2019

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

The goal of this study was to perform an extensive temporal characterization of the early pathologic processes in the streptozotocin (STZ)-induced diabetic retinopathy (DR) mouse model, beyond the vascular phenotype, and to investigate the potential of clinically relevant compounds in attenuating these processes. METHODS. Visual acuity and contrast sensitivity (CS) were studied in the mouse STZ model until 24 weeks postdiabetes onset. ERG, spectral domain optical coherence tomography (SD-OCT), leukostasis, and immunohistochemistry were applied to investigate neurodegeneration, inflammation, and gliosis during early-, mid-and late-phase diabetes. Aflibercept or triamcinolone acetonide (TAAC) was administered to investigate their efficacy on the aforementioned processes. RESULTS. Visual acuity and CS loss started at 4 and 18 weeks postdiabetes onset, respectively, and progressively declined over time. ERG amplitudes were diminished and OP latencies increased after 6 weeks, whereas SD-OCT revealed retinal thinning from 4 weeks postdiabetes. Immunohistochemical analyses linked these findings to retinal ganglion and cholinergic amacrine cell loss at 4 and 8 weeks postdiabetes onset, respectively, which was further decreased after aflibercept administration. The number of adherent leukocytes was augmented after 2 weeks, whereas increased micro-and macroglia reactivity was present from 4 weeks postdiabetes. Aflibercept or TAAC showed improved efficacy on inflammation and gliosis. CONCLUSIONS. STZ-induced diabetic mice developed early pathologic DR hallmarks, from which inflammation seemed the initial trigger, leading to further development of functional and morphologic retinal changes. These findings indicate that the mouse STZ model is suitable to study novel integrative non-vascular therapies to treat early DR.

show abstract

“…In addition, MMPs play a central role in the direct activation of signaling molecules, such as tumor necrosis factor (TNF) and other cytokines; MMPs therefore contribute to various aspects of immunity [ 48 ]. A detailed classification of MMPs and TIMPs, based on their substrates, general biological effect, localization in the eye, and processes in which they take part, is provided in the Supplementary Table S1 [ 16 , 17 , 32 , 38 , 41 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Extracellular Matrix In the Eye And The Metalloproteinasementioning

confidence: 99%

Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD)

García-Onrubia

Valentín-Bravo

Coco‐Martín

et al. 2020

IJMS

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is the leading cause of vision loss and legal blindness among the elderly. Although the pathogenesis of AMD is still barely understood, recent studies have reported that disorders in the regulation of the extracellular matrix (ECM) play an important role in its etiopathogenesis. The dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). The present review focuses on the crucial processes that occur at the level of the Bruch’s membrane, with special emphasis on MMPs, TIMPs, and the polymorphisms associated with increased susceptibility to AMD development. A systematic literature search was performed, covering the years 1990–2020, using the following keywords: AMD, extracellular matrix, Bruch’s membrane, MMPs, TIMPs, and MMPs polymorphisms in AMD. In both early and advanced AMD, the pathological dynamic changes of ECM structural components are caused by the dysfunction of specific regulators and by the influence of other regulatory systems connected with both genetic and environmental factors. Better insight into the pathological role of MMP/TIMP complexes may lead to the development of new strategies for AMD treatment and prevention.

show abstract

MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

Cited by 31 publications

References 89 publications

Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury

Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD)

Contact Info

Product

Resources

About