A Naturally Fluorescent <i>Mgp</i> Transgenic Mouse for Angiogenesis and Glaucoma Longitudinal Studies

Asokan, Priyadarsini; Mitra, Riten; Periasamy, Ramesh; Han, Zongchao; Borrás, Teresa

doi:10.1167/iovs.17-22992

Cited by 14 publications

(23 citation statements)

References 37 publications

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“…Our key finding was that even with multiple adjustments applied CRAE and AVR at follow-up were smaller with higher circulating levels of dp-ucMGP at baseline. Our findings are compatible with studies showing expression of MGP in capillaries and small arterioles 15 and in particular in the glaucoma-relevant tissues of the eye and the retinal microvasculature 16 – 20 . Our findings underscore the pivotal role of activated MGP in maintaining ocular homeostasis and are in line with our previous report, which showed that high dp-ucMGP predicted adverse health outcomes, including total, non-cancer and cardiovascular mortality in 2318 FLEMENGHO participants followed up for a median of 14.1 years 11 .…”

Section: Discussionsupporting

confidence: 93%

“…A novel MGP transgenic mouse model allows visualising angiogenesis- and glaucoma-relevant tissues by natural fluorescence 20 . These mice have normal intra-ocular pressure.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, MGP is abundantly expressed in the eye 16 – 19 , where it takes part in preserving the structural integrity of the trabecular meshwork (TM)16,17, the sclera 18 and the retinal ganglion cells 19 . A naturally fluorescent MGP transgenic mouse model also demonstrated MGP expression in the retinal vasculature 20 . In view of these observations 13 – 20 , we hypothesised that retinal microvascular traits, as exemplified by retinal arteriolar and venular diameters, might be associated with inactive dp-ucMGP.…”

Section: Introductionmentioning

confidence: 91%

“…A naturally fluorescent MGP transgenic mouse model also demonstrated MGP expression in the retinal vasculature 20 . In view of these observations 13 – 20 , we hypothesised that retinal microvascular traits, as exemplified by retinal arteriolar and venular diameters, might be associated with inactive dp-ucMGP. We assessed in the Flemish Study on Environment, Genes, and Health Outcomes (FLEMENGHO) 11 , 14 whether circulating inactive dp-ucMGP predicted retinal microvascular diameters 11 years after the measurement of the biomarker.…”

Section: Introductionmentioning

confidence: 91%

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Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Wei

Huang

Zhang

et al. 2018

Sci Rep

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Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confidence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03 µm (CI, −1.96 to −0.11; P = 0.028) and −0.007 (CI, −0.011 to −0.002; P = 0.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates −0.91 µm (CI, −1.82 to −0.01; P = 0.048) and −0.006 (95% CI, −0.011 to −0.001; P = 0.014), respectively. Circulating inactive dp–ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.

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Section: Discussionsupporting

confidence: 93%

“…A novel MGP transgenic mouse model allows visualising angiogenesis- and glaucoma-relevant tissues by natural fluorescence 20 . These mice have normal intra-ocular pressure.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 91%

See 2 more Smart Citations

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Wei

Huang

Zhang

et al. 2018

Sci Rep

View full text Add to dashboard Cite

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“…Released active MGP acts as a local inhibitor of calcification [233,234]. MGP is also ubiquitously expressed in multiple organs, and it is likely that this widespread expression of MGP has considerably more functions than are known for local inhibitor of calcification [235][236][237][238][239]. Recently, plasma dephospho-uncarboxylated MGP (dp-ucMGP) is used as a biomarker reflecting pool vitamin K status.…”

Section: Matrix Gla Protein (Mgp)mentioning

confidence: 99%

Vascular Calcification—New Insights into Its Mechanism

Lee

Jeon

2020

IJMS

283

254

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Vascular calcification (VC), which is categorized by intimal and medial calcification, depending on the site(s) involved within the vessel, is closely related to cardiovascular disease. Specifically, medial calcification is prevalent in certain medical situations, including chronic kidney disease and diabetes. The past few decades have seen extensive research into VC, revealing that the mechanism of VC is not merely a consequence of a high-phosphorous and -calcium milieu, but also occurs via delicate and well-organized biologic processes, including an imbalance between osteochondrogenic signaling and anticalcific events. In addition to traditionally established osteogenic signaling, dysfunctional calcium homeostasis is prerequisite in the development of VC. Moreover, loss of defensive mechanisms, by microorganelle dysfunction, including hyper-fragmented mitochondria, mitochondrial oxidative stress, defective autophagy or mitophagy, and endoplasmic reticulum (ER) stress, may all contribute to VC. To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, we provide this review of a detailed updated molecular mechanism of VC. This encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.

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Deletion of transcription factor AP‐2β from the developing murine trabecular meshwork region leads to progressive glaucomatous changes

Taiyab

Akula

Dham

et al. 2021

J of Neuroscience Research

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Glaucoma is one of the leading causes of irreversible blindness and can result from abnormalities in anterior segment structures required for aqueous humor outflow, including the trabecular meshwork (TM) and Schlemm's canal (SC). Transcription factors such as AP‐2β play critical roles in anterior segment development. Here, we show that the Mgp‐Cre knock‐in (Mgp‐Cre.KI) mouse can be used to target the embryonic periocular mesenchyme giving rise to the TM and SC. Fate mapping of male and female mice indicates that AP‐2β loss causes a decrease in iridocorneal angle cells derived from Mgp‐Cre.KI‐expressing populations compared to controls. Moreover, histological analyses revealed peripheral iridocorneal adhesions in AP‐2β mutants that were accompanied by a decrease in expression of TM and SC markers, as observed using immunohistochemistry. In addition, rebound tonometry showed significantly higher intraocular pressure (IOP) that was correlated with a progressive significant loss of retinal ganglion cells, reduced retinal thickness, and reduced retinal function, as measured using an electroretinogram, in AP‐2β mutants compared with controls, reflecting pathology described in late‐stage glaucoma patients. Importantly, elevated IOP in AP‐2β mutants was significantly reduced by treatment with latanoprost, a prostaglandin analog that increases unconventional outflow. These findings demonstrate that AP‐2β is critical for TM and SC development, and that these mutant mice can serve as a model for understanding and treating progressive human primary angle‐closure glaucoma.

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A Naturally Fluorescent Mgp Transgenic Mouse for Angiogenesis and Glaucoma Longitudinal Studies

Cited by 14 publications

References 37 publications

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Vascular Calcification—New Insights into Its Mechanism

Deletion of transcription factor AP‐2β from the developing murine trabecular meshwork region leads to progressive glaucomatous changes

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