Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions

Lipécz, Ágnes; Miller, Lauren R.; Kovács, Illés; Czakó, Cecília; Csípő, Tamás; Baffi, Judit; Csiszár, Anna; Tarantini, Stefano; Ungvári, Zoltán; Yabluchanskiy, Andriy; Conley, Shannon M.

doi:10.1007/s11357-019-00138-3

Cited by 53 publications

(39 citation statements)

References 300 publications

(351 reference statements)

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“…Combined with the metaregression results, whether to adjust for hepatitis B infection may be the source of heterogeneity. Some studies have shown that hepatitis B infection is also a risk factor for AMD [ 32 ], and only a study by Shin et al [ 21 ] adjusted this confounding factor; smoking, hypertension, and CVD are common risk factors for PD and AMD [ 6 , 33 ]. The results of the subgroup analysis show that the above three factors may cooperate with PD to increase the risk of AMD; diabetes is also a common risk factor for PD and AMD [ 11 , 34 ], but our subgroup analysis results show that after adjusting for the confounding factor of diabetes, the correlation between PD and AMD was higher.…”

Section: Discussionmentioning

confidence: 99%

Periodontal Disease and Age-Related Macular Degeneration: A Meta-Analysis of 112,240 Participants

Fang

et al. 2020

BioMed Research International

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Objective. Epidemiological studies have shown a correlation between periodontal disease (PD) and age-related macular degeneration (AMD). However, the results have been inconsistent, and no relevant meta-analysis has been performed on this topic. Hence, we performed a meta-analysis to evaluate whether the two diseases are related. Material and Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to April 20, 2020, for related articles. Two authors independently conducted literature screening and data extraction and then used the Stata 15.1 software to calculate the relative risk (RRs) and 95% confidence intervals (CIs) to assess the association between PD and AMD. Results. A total of 5 observational studies involving 112,240 participants and 5,005 AMD patients were included. The results of meta-analysis using the random-effects model showed that the incidence of AMD in PD patients was 1.35 times that of non-PD patients; the difference was statistically significant ( RR = 1.35 , 95 % CI = 1.07 – 1.70 , P = 0.011 ). Sensitivity analysis showed that the results were stable. Conclusions. PD patients have a higher risk of AMD, but the causal relationship between PD and AMD has not been confirmed. Further research should be carried out to verify the exact relationship between the two.

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Section: Discussionmentioning

confidence: 99%

Periodontal Disease and Age-Related Macular Degeneration: A Meta-Analysis of 112,240 Participants

Fang

et al. 2020

BioMed Research International

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“…On the other hand, recent two comprehensive review articles substantiate the evidence for microvascular contributions to age-related vascular pathobiology that affect microvascular density, and also the recent findings showing the role of exercise in the reversal in microvascular rarefaction is potentially mediated by insulin-like growth factor-1 (IFG-1) [ 35 , 36 ]. Accumulating clinical and laboratory evidence indicate the role of exercise-induced increases in blood flow in improving vascular integrity and stimulating neovascularization via the actions of IGF-1 in aged humans and animals.…”

Section: Discussionmentioning

confidence: 89%

Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice

Yue

Jiang

et al. 2020

Stem Cells International

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Background. Aging is a major risk factor for cardiovascular disease. Cysteine protease cathepsin K (CatK) has been implicated in the process of angiogenesis, but the exact roles of individual CatK in vessel formation during aging are poorly understood. Methods and Results. To study the putative role of CatK in ischemia-induced angiogenesis, we applied a hindlimb ischemia model to aged wild-type (CatK+/+) and CatK-deficient (CatK−/−) mice. A serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in the aged CatK−/−mice was impaired throughout the follow-up period. On postoperative day 14, CatK deficiency had also impaired capillary formation. CatK deficiency reduced the levels of cleaved Notch1, phospho-Akt, and/or vascular endothelial growth factor (VEGF) proteins in the ischemic muscles and bone marrow-derived c-Kit+ cells. A flow cytometry analysis revealed that CatK deficiency reduced the numbers of endothelial progenitor cell (EPC)-like CD31+/c-Kit+ cells in the peripheral blood as well as the ischemic vasculature. In vitro experiments, CatK−/− impaired bone-derived c-Kit+ cellular functions (migration, invasion, proliferation, and tubulogenesis) in aged mice. Our findings demonstrated that aging impaired the ischemia-induced angiogenesis associated with the reductions of the production and mobilization of CD31+/c-Kit+ cells in mice. Conclusions. These findings established that the impairment of ischemia-induced neovascularization in aged CatK−/− mice is due, at least in part, to the reduction of EPC mobilization and the homing of the cells into vasculature that is associated with the impairment of Notch1 signaling activation at advanced ages.

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“…Since 2010, AMD has become the 3rd most common cause of blindness and the 4th leading cause of visual impairment worldwide (23). IGFs, the family of important proteins that regulate various cellular processes, including proliferation, differentiation, apoptosis and neovascularization, may be involved in molecular mechanisms that contribute to the pathogenesis of aMd, involving oxidative stress, mitochondrial dysfunction and impaired resistance to molecular stressors in the choriocapillaris (24)(25)(26)(27)(28)(29)(30). The members of the IGF family, including IGFBP-2, IGFBP-6 and IGFBP-rP1, were demonstrated to be increased in patients with exudative aMd (31).…”

Section: Discussionmentioning

confidence: 99%

IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway

et al. 2020

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insulin-like growth factor binding protein-related protein 1 (iGFBP-rP1) has been reported to have various functions in different cellular contexts. our previous investigation discovered that iGFBP-rP1 inhibited retinal angiogenesis in vitro and in vivo by inhibiting the pro-angiogenic effect of VeGF and downregulating VeGF expression. recently, IGFBP-rP1 was confirmed to be downregulated in the aqueous humor of patients with neovascular age-related macular degeneration compared with controls; however, its specific role remains unknown. The present study applied the technique of gene silencing, reverse transcription-quantitative PCR, western blotting, cell viability assays, cell motility assays and tube formation assays. Chemical hypoxic conditions and choroidal endothelial (rF/6a) cells were used to explore the effect of iGFBP-rP1-silencing on the phenotype activation of rF/6a cells under hypoxic conditions and to elucidate the underlying mechanisms. siRNA achieved IGFBP-rP1-silencing in RF/6A cells without cytotoxicity. IGFBP-rP1-silencing significantly restored the viability of rF/6a cells in hypoxia and enhanced hypoxia-induced migration and capillary-like tube formation of RF/6A cells. Furthermore, IGFBP-rP1-silencing significantly upregulated the expression of B-raF, phosphorylated (p)-MeK, perK and VeGF in rF/6a cells under hypoxic conditions; however, these upregulations were inhibited by exogenous iGFBP-rP1. These data indicated that silencing IGFBP-rP1 expression in RF/6A cells effectively promoted the hypoxia-induced angiogenic potential of choroidal endothelial cells by upregulating raF/MeK/erK signaling pathway activation and VeGF expression.

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Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions

Cited by 53 publications

References 300 publications

Periodontal Disease and Age-Related Macular Degeneration: A Meta-Analysis of 112,240 Participants

Periodontal Disease and Age-Related Macular Degeneration: A Meta-Analysis of 112,240 Participants

Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice

IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway

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