Cross-Inhibition of Norrin and TGF-β Signaling Modulates Development of Retinal and Choroidal Vasculature

Seitz, R; Weber, G.; Albrecht, Sebastian; Fuchshofer, Rudolf; Tamm, Ernst R.; Ohlmann, Andreas

doi:10.1167/iovs.17-23403

Cited by 8 publications

(7 citation statements)

References 59 publications

(85 reference statements)

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“…The tunel staining and immunohistochemistry procedures were adapted from a previous study with slight modification. 24,25 The paraffinembedded tissue was subjected to standard procedures for embedding, sectioning, and dehydration. Subsequently, the tissue was treated with a proteinase K working solution for repair, followed by the addition of a membrane-breaking working solution to cover the tissue.…”

Section: Biochemical Indicator Analysismentioning

confidence: 99%

Beneficial effect of ζ-carotene-like compounds on acute UVB irradiation by alleviating inflammation and regulating intestinal flora

Zhang,

Wang,

Liang

et al. 2023

Food Funct.

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Section: Biochemical Indicator Analysismentioning

confidence: 99%

Beneficial effect of ζ-carotene-like compounds on acute UVB irradiation by alleviating inflammation and regulating intestinal flora

Zhang,

Wang,

Liang

et al. 2023

Food Funct.

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“…In addition, norrin has weak sequence homology with TGF-β family proteins, and maternal Xenopus norrin is suggested as an antagonist of BMP4/TGF-β activities (Xu et al, 2012). Cross-inhibition of norrin and TGFβ was also reported in transgenic mice over-expressing either norrin or TGF-β in the lens (Seitz et al, 2018), suggesting that loss of inhibition of TGF-β may contribute in part to Norrie disease (Xu et al, 2012). So far no genetic mutations in either angiopoetin-2 or TGFβ mutations have been linked with human FEVR.…”

Section: Which Factors Drive Wnt-related Retinal Vascular Defects?mentioning

confidence: 99%

Wnt Signaling in vascular eye diseases

Wang

Liu

Huang

et al. 2019

Progress in Retinal and Eye Research

137

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The Wnt signaling pathway plays a pivotal role in vascular morphogenesis in various organs including the eye. Wnt ligands and receptors are key regulators of ocular angiogenesis both during the eye development and in vascular eye diseases. Wnt signaling participates in regulating multiple vascular beds in the eye including regression of the hyaloid vessels, and development of structured layers of vasculature in the retina. Loss-of-function mutations in Wnt signaling components cause rare genetic eye diseases in humans such as Norrie disease (ND), and familial exudative vitreoretinopathy (FEVR) with defective ocular vasculature. On the other hand, experimental studies in the more prevalent vascular eye diseases, such as wet age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), and corneal neovascularization, suggest that aberrantly increased Wnt signaling is one of the causations for pathological ocular neovascularization, indicating the potential of modulating Wnt signaling to ameliorate pathological angiogenesis in eye diseases. This review recapitulates the key roles of the Wnt signaling pathway during ocular vascular development and in vascular eye diseases, and pharmaceutical approaches targeting the Wnt signaling as potential treatment options.

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“…Strong evidence for antiangiogenic function of TGF-β in nAMD derives from in-vivo studies that are not based on LI-CNV ( Figure 3 ). In a transgenic mouse model, ocular overexpression of active TGF-β1 induced the atrophy of choriocapillaris without any sign of CNV [ 69 , 70 ]. Specularly, in the developing eyes of mice lacking Tgf-β2 (Tgfb2 −/− ), persistent vitreous vessels could be detected [ 50 ].…”

Section: Evidence For Antiangiogenic Function Of Tgf-β In Namdmentioning

confidence: 99%

The Controversial Role of TGF-β in Neovascular Age-Related Macular Degeneration Pathogenesis

Tosi

Orlandini

Galvagni

2018

IJMS

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The multifunctional transforming growth factors-beta (TGF-βs) have been extensively studied regarding their role in the pathogenesis of neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Despite this, their effect remains somewhat controversial. Indeed, both pro- and antiangiogenic activities have been suggested for TGF-β signaling in the development and progression of nAMD, and opposite therapies have been proposed targeting the inhibition or activation of the TGF-β pathway. The present article summarizes the current literature linking TGF-β and nAMD, and reviews experimental data supporting both pro- and antiangiogenic hypotheses, taking into account the limitations of the experimental approaches.

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Cross-Inhibition of Norrin and TGF-β Signaling Modulates Development of Retinal and Choroidal Vasculature

Abstract: High amounts of TGF-β in the eye cause a substantial reduction in the activity of Wnt/β-catenin signaling. This effect is inhibited in the presence of high amounts of Norrin, which further induce the expression of SMAD7 to inhibit TGF-β signaling.

Cited by 8 publications

References 59 publications

Beneficial effect of ζ-carotene-like compounds on acute UVB irradiation by alleviating inflammation and regulating intestinal flora

Beneficial effect of ζ-carotene-like compounds on acute UVB irradiation by alleviating inflammation and regulating intestinal flora

Wnt Signaling in vascular eye diseases

The Controversial Role of TGF-β in Neovascular Age-Related Macular Degeneration Pathogenesis

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