Wnt signaling in age-related macular degeneration: human macular tissue and mouse model

Tuo, Jingsheng; Wang, Yujuan; Cheng, Rui; Li, Yichao; Chen, Mei; Qiu, Fangfang; Qian, Haohua; Shen, Defen; Peñalva, Rosana; Xu, Heping; Xing, Jian; Chan, Chi Chao

doi:10.1186/s12967-015-0683-x

Cited by 38 publications

(49 citation statements)

References 56 publications

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“…For example, the Wnt signaling pathway, which is important for osteoblast differentiation and bone formation, can affect the progression of AMD. 44,45 In the present study, no significant results were derived for men, possibly because of the low prevalence of osteoporosis and AMD. An increased prevalence of drusen and neovascular AMD in women has been documented in previous reports.…”

Section: Discussioncontrasting

confidence: 66%

Association Between Osteoporosis and Age-Related Macular Degeneration: The Korea National Health and Nutrition Examination Survey

Yoo

Kim

Kwak

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Previous studies have reported a possible link between low bone mineral density and AMD. The aim of the present study was to investigate the association between osteoporosis and AMD in a South Korean cohort. METHODS. This cross-sectional, nationwide study included 3496 women and 2789 men who had participated in the Korean National Health and Nutrition Examination Survey from 2008 to 2011. All retinal photographs were graded using an international classification and grading system. Osteoporosis was assessed using dual-energy x-ray absorptiometry. Multivariate logistic regression analysis was performed to examine the relationship between osteoporosis and AMD after adjustment for potential confounders, including age, the body mass index, dietary calcium intake, and the serum vitamin D level. The odds ratios (OR) for other agingrelated eye diseases, including cataract, open-angle glaucoma, and diabetic retinopathy, were analyzed in accordance with the presence of osteoporosis. RESULTS. Multivariate regression analysis revealed that osteoporosis was significantly associated with all types of AMD (early and late: OR, 1.31; P ¼ 0.017) and early AMD (OR, 1.36; P ¼ 0.007) in women. Late AMD was not associated with osteoporosis (OR, 0.84; P ¼ 0.670). In men, osteoporosis was not associated with any type of AMD. In women, the status of osteoporosis in the femoral neck showed a linear relationship with AMD (P ¼ 0.004). Although osteoporosis was associated with AMD in women, it showed no association with other age-related eye diseases; this suggested a disease-specific association. CONCLUSIONS. Our findings suggest that osteoporosis plays a role in AMD development in postmenopausal women.

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Section: Discussioncontrasting

confidence: 66%

Association Between Osteoporosis and Age-Related Macular Degeneration: The Korea National Health and Nutrition Examination Survey

Yoo

Kim

Kwak

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Wnt/β-catenin signaling pathway is reported to play key roles in the production of inflammatory and angiogenic molecules in the diabetic retina. 31 In retinal vascular complications, the Wnt ligand binds to its receptor Fz (frizzled) and co-receptor LRP-5 or LRP-6 to inactivate GSK-3β, resulting in the stabilization and cytosolic accumulation β-catenin that leads to its nuclear translocation and subsequent upregulation in the transcription of the pro-inflammatory genes VEGF, HIF-1α, and ICAM-1 32 . In our study, diabetic mice had significantly ( p < 0.05) lower expression of LRP-1, but higher ( p < 0.05) LRP-6, β-catenin, and related pro-inflammatory molecules compared to non-diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

LRP-1 Pathway Targeted Inhibition of Vascular Abnormalities in the Retina of Diabetic Mice

Hossain

Tauhid

Davenport

et al. 2016

Current Eye Research

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Purpose The cell surface LDL (low-density lipoprotein) receptor-related protein-1 (LRP-1) is important for lipid transport and several cell signaling processes. Human apolipoprotein E (apoE) is a ligand of LRP-1. We previously reported that a short peptide (apoEdp) mimicking the LRP-1 binding region of apoE prevents hyperglycemia-induced retinal endothelial cell dysfunction in vitro. The in-vivo outcome of apoE-based peptidomimetic inhibition of LRP-1 in the treatment of diabetic retinopathy is unknown. Methods Six months after streptozotocin induction of diabetes, male C57Bl/6 mice were intravitreally inoculated with apoEdp in a controlled release formulation. On the 15th day post-apoEdp treatment, mouse retinas were harvested to examine (1) blood–retinal–barrier (BRB) permeability by Evans blue dye, inflammatory leukostasis by concanavalin staining of leukocytes and LRP-1 pathway-related protein expression by Western blot analysis and gelatin zymography. Results Intravitreal apoEdp treatment of diabetic mice significantly reduced Evans blue extravasation and the number of adherent leukocytes in the diabetic mouse retinas. ApoEdp treatment inhibited the expression of extracellular matrix (ECM) degrading proteases heparanase and MMP-2, and restores the BRB tight junction proteins occludin and ZO-1. ApoEdp treatment also inhibited Wnt/β-catenin-related expression of pro-inflammatory molecules ICAM-1, HIF-1α, and VEGF through negative regulation by LRP-1. Conclusion Intravitreal apoEdp treatment of diabetic mice resulted a significant decrease in retinal vascular abnormalities through downregulation of LRP-1-related ECM protein degradation and Wnt/β-catenin-related pro-angiogenic molecules.

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“…Transcriptomic profiling of AMD retinas further revealed upregulation of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1(NUCKS1), which acts as a substrate for CDK1 during mitosis [128]. In addition, elevated mRNA expression levels of cyclin-D as a proliferation associated altered Wnt signalling pathway regulation was reported in both animal models and macular tissues from AMD patients [129].…”

Section: Glaucoma and Age-related Retinal Disordersmentioning

confidence: 99%

Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development

Joseph¹,

Mangani²,

Gupta³

et al. 2020

Aging and disease

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Cell cycle dysregulation has been implicated in the pathogenesis of neurodegenerative disorders. Specialised function obligates neuronal cells to subsist in a quiescent state of cell cycle once differentiated and therefore the circumstances and mechanisms underlying aberrant cell cycle activation in post-mitotic neurons in physiological and disease conditions remains an intriguing area of research. There is a strict requirement of concurrence to cell cycle regulation for neurons to ensure intracellular biochemical conformity as well as interrelationship with other cells within neural tissues. This review deliberates on various mechanisms underlying cell cycle regulation in neuronal cells and underscores potential implications of their non-compliance in neural pathology. Recent research suggests that successful duplication of genetic material without subsequent induction of mitosis induces inherent molecular flaws that eventually assert as apoptotic changes. The consequences of anomalous cell cycle activation and subsequent apoptosis are demonstrated by the increased presence of molecular stress response and apoptotic markers. This review delineates cell cycle events under normal physiological conditions and deficits amalgamated by alterations in protein levels and signalling pathways associated with cell-division are analysed. Cell cycle regulators essentially, cyclins, CDKs, cip/kip family of inhibitors, caspases, bax and p53 have been identified to be involved in impaired cell cycle regulation and associated with neural pathology. The pharmacological modulators of cell cycle that are shown to impart protection in various animal models of neurological deficits are summarised. Greater understanding of the molecular mechanisms that are indispensable to cell cycle regulation in neurons in health and disease conditions will facilitate targeted drug development for neuroprotection.

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Wnt signaling in age-related macular degeneration: human macular tissue and mouse model

Cited by 38 publications

References 56 publications

Association Between Osteoporosis and Age-Related Macular Degeneration: The Korea National Health and Nutrition Examination Survey

Association Between Osteoporosis and Age-Related Macular Degeneration: The Korea National Health and Nutrition Examination Survey

LRP-1 Pathway Targeted Inhibition of Vascular Abnormalities in the Retina of Diabetic Mice

Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development

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