Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells

Cui, Bohao; Xu, Guowang; Zhou, Wei; Zhang, Xiaodan; He, Kai; Bai, Tinghui; Lin, Dongxue; Wei-Zhang, Selena; Zhao, Yan; Liu, Shengnan; Zhou, Hui; Wang, Qing; Yao, Xueming; Song, Ying; Xie, Ruotian; Duan, Xue; Lei, Yi; Du, Mei; Chang, Yongsheng; Xu, Heping; Zhou, Dongming; Yu, Ying; Wang, Xiaohong; Yan, Hua

doi:10.1016/j.metabol.2023.155584

Cited by 13 publications

(11 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We herein found a lower take rate of transplanted islets in the AIM2 −/− group, which was due to a reduced graft revascularization. In line with this result, Cui et al [53] could show in a model of laser-induced choroidal neovascularization that the loss of AIM2 significantly inhibits vascular leakage, blood vessel formation, and lesion thickness [53]. These findings could be explained by the higher levels of IFN-β/γ, which have been demonstrated to repress angiogenesis [37,38,54].…”

Section: Discussionmentioning

confidence: 79%

Absent in Melanoma (AIM)2 Promotes the Outcome of Islet Transplantation by Repressing Ischemia-Induced Interferon (IFN) Signaling

Wrublewsky,

Wilden,

Bickelmann

et al. 2023

Cells

View full text Add to dashboard Cite

Clinical islet transplantation is limited by ischemia-induced islet cell death. Recently, it has been reported that the absent in melanoma (AIM)2 inflammasome is upregulated by ischemic cell death due to recognition of aberrant cytoplasmic self-dsDNA. However, it is unknown whether AIM2 determines the outcome of islet transplantation. To investigate this, isolated wild type (WT) and AIM2-deficient (AIM2−/−) islets were exposed to oxygen-glucose deprivation to mimic ischemia, and their viability, endocrine function, and interferon (IFN) signaling were assessed. Moreover, the revascularization and endocrine function of grafted WT and AIM2−/− islets were analyzed in the mouse dorsal skinfold chamber model and the diabetic kidney capsule model. Ischemic WT and AIM2−/− islets did not differ in their viability. However, AIM2−/− islets exhibited a higher protein level of p202, a transcriptional regulator of IFN-β and IFN-γ gene expression. Accordingly, these cytokines were upregulated in AIM2−/− islets, resulting in a suppressed gene expression and secretion of insulin. Moreover, the revascularization of AIM2−/− islet grafts was deteriorated when compared to WT controls. Furthermore, transplantation of AIM2−/− islets in diabetic mice failed to restore physiological blood glucose levels. These findings indicate that AIM2 crucially determines the engraftment and endocrine function of transplanted islets by repressing IFN signaling.

show abstract

Section: Discussionmentioning

confidence: 79%

Absent in Melanoma (AIM)2 Promotes the Outcome of Islet Transplantation by Repressing Ischemia-Induced Interferon (IFN) Signaling

Wrublewsky,

Wilden,

Bickelmann

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

“…Recently, several population-based multi-cohort studies have reported that high levels of physical activity and exercise can have a protective effect against AMD progression ( 23 , 24 , 40 ). Furthermore, a recent study involving human subjects and animals reports that the beneficial effect of exercise on AMD could be attributed, in part, to its anti-inflammatory effects, particularly in attenuating VAT inflammation ( 41 ). Notably, in a previous study, we observed a reduction in VAT SUVmax after 3 months of exercise in women with obesity ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic activity of visceral adipose tissue is associated with age-related macular degeneration: a pilot 18F-FDG PET/CT study

Choi,

Joung,

Pahk

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundObesity is known to increase the risk and severity of age-related macular degeneration (AMD). Increased inflamed metabolic activity of visceral adipose tissue (VAT) is considered as a crucial underlying mechanism for the harmful effects of obesity. In this study, we aimed to investigate the inflamed metabolic activity of VAT with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and their association with AMD.Materials and methodsA total of 57 elderly participants (aged ≥ 50 years) who underwent 18F-FDG PET/CT for health screening and subsequent fundoscopic exam for complaint of recently impaired vision were enrolled. The metabolic activity of VAT was measured from the maximum standardized uptake value (SUVmax) of VAT. The early AMD participant was defined as the participant with either eye satisfying AMD and without any sign of advanced AMD (neovascular AMD or geographic atrophy). The late AMD participant was defined as the participant with either eye satisfying advanced AMD.ResultsVAT SUVmax was highest in participants with late AMD, intermediate in early AMD, and lowest in non-AMD participants. The levels of systemic inflammation surrogate markers were also highest in late AMD group. Furthermore, VAT SUVmax was positively correlated with systemic inflammation surrogate markers and independently associated with the late AMD.ConclusionsThe metabolic activity of VAT evaluated by 18F-FDG PET/CT was associated with the severity of AMD and synchronized with the level of systemic inflammation. Thus, VAT SUVmax could be potentially employed as a surrogate marker of obesity-driven VAT inflammation associated with AMD.

show abstract

“…Recent studies observed that AIM2/NLRP2 inflammasome (predominantly expressed in microglia) was most copiously expressed in the retina-choroid complex. They found that the expression of AIM2 was significantly induced during CNV pathogenesis which was significantly attenuated by treadmill training exercise in rodents [88]. Physical exercise mitigates neovascular AMD by suppressing the AIM2 inflammasome in myeloid cells.…”

Section: Exercise Apn/adipors Signaling and Neovascular Amdmentioning

confidence: 98%

“…Moreover, earlier proteomic data directed that physical exercise facilitated the secretion of APN [9], from fat to circulation, which in turn, led to a decrease in ROS-induced DNA damage and the inhibition of AIM2 inflammasome activation in myeloid cells within eyes affected by choroidal neovascularization (CNV), and this effect was facilitated through the AMPK-p47phox pathway. Findings from earlier studies suggested that in sedentary AdipoQ-deficient (APNKO) mice, there was a tendency for an enhanced leakage area and choroidal neovascularization (CNV) volume when compared to sedentary wild-type mice [88]. Furthermore, this difference became more pronounced in exercised mice, implying that APN plays an essential role in the positive effects observed in exercised mice [89].…”

Section: Exercise Apn/adipors Signaling and Neovascular Amdmentioning

confidence: 99%

“…Physical exercise has the potential to excite the systemic and localized production of APN, offering a protective effect in various ocular conditions, including but not limited to DR, AMD, retinitis pigmentosa (RP), glaucoma, and light-induced retinal degeneration [88]. Engaging in daily physical exercise seems to provide a safeguard against the development of neovascular AMD.…”

Section: Exercise Apn/adipors Signaling and Neovascular Amdmentioning

confidence: 99%

See 1 more Smart Citation

Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD)

Choubey,

Tirumalasetty,

Bora

et al. 2023

Biomedicines

View full text Add to dashboard Cite

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN’s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue’s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging.

show abstract

Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells

Cited by 13 publications

References 51 publications

Absent in Melanoma (AIM)2 Promotes the Outcome of Islet Transplantation by Repressing Ischemia-Induced Interferon (IFN) Signaling

Absent in Melanoma (AIM)2 Promotes the Outcome of Islet Transplantation by Repressing Ischemia-Induced Interferon (IFN) Signaling

Metabolic activity of visceral adipose tissue is associated with age-related macular degeneration: a pilot 18F-FDG PET/CT study

Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD)

Contact Info

Product

Resources

About