Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Age Related Macular Degeneration, Role in Pathophysiology, and Possible New Therapeutic Strategies

Bilbao-Malavé, Valentina; González-Zamora, Jorge; Puente, Miriam de la; Recalde, Sergio; Fernández-Robredo, Patricia; Hernández, María; Layana, Alfredo García; Viteri, Manuel Sáenz de

doi:10.3390/antiox10081170

Cited by 20 publications

(12 citation statements)

References 205 publications

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“…Monocytes, alveolar cells and eosinophils express the HN receptors, but the highest expression of these receptors is found in lung macrophages 18 . Human primary mitochondrial diseases (mitochondrial DNA mutations and nuclear DNA mutations in mitochondrial-targeted proteins) and diseases associated with mitochondrial dysfunction are characterized by high circulating HN levels 19 – 23 . However, no studies to date have examined serum HN levels in COPD.…”

Section: Introductionmentioning

confidence: 99%

Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study

Diago

Martín-Audera

Agüero

et al. 2022

Sci Rep

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Mitokines (Humanin (HN), GDF15 and FGF21) are produced as a result of mitochondrial dysfunction and may have major roles in chronic inflammation, malnutrition and exercise capacity in people with COPD. Except for GDF15, studies on this subject are lacking. A total of 165 patients with stable COPD and 49 smokers without COPD were enrolled. We assessed their serum mitokine levels and clinical characteristics at baseline. We recorded moderate and severe exacerbation for the next 12 months. Baseline serum HN (p = 0.037) and GDF-15 (p = 0.013) levels were higher in the COPD group. High HN levels were independently associated with a high risk of exacerbation (HRE) (OR 2.798, 95% CI 1.266–6.187, p = 0.011), malnutrition (OR 6.645, 95% CI 1.859–23.749, p = 0.004), and 6MWD (OR 0.995, 95% CI 0.991–0.999, p = 0.008), and future moderate (HR 1.826, 95% CI 1.181–2.822, p = 0.007) and severe exacerbations (HR 3.445, 95% CI 1.357–8.740, p = 0.009). High GDF15 levels were associated with HRE (OR 3.028, 95% CI 1.134–8.083, p = 0.027), 6MWD (OR 0.995, 95% CI 0.990–0.999, p = 0.017) and predicted desaturation in 6MWT (OR 3.999, 95% CI 1.487–10.757, p = 0.006). High FGF21 levels were associated with HRE (OR 2.144, 95% CI 1.000–4.600, p = 0.05), and predicted future severe exacerbation (HR 4.217, 95% CI 1.459–12.193, p = 0.008). The mitokine levels were higher in patients with COPD than smokers without COPD, and were associated with important clinical outcomes such as exercise capacity and COPD exacerbation. Among the mitokines, HN showed the strongest association with COPD and may serve as a future risk biomarker in this disease.Trial registation NCT04449419.

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Section: Introductionmentioning

confidence: 99%

Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study

Diago

Martín-Audera

Agüero

et al. 2022

Sci Rep

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“…In the early stages of AMD, choriocapillaris dropout [ 20 ], oxidative stress [ 6 ], and a pro-inflammatory state [ 21 ] promote an environment in which the combination of stimulatory signals released by the retina, RPE, and choroid prompts remodelling of the vasculature. In ARPE-19 cells, oxidative stress conditions (as observed in AMD) could activate MMP10.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress is one of the main causes leading to ageing and consequently it has been found to play a central role in many neurodegenerative diseases, including AMD [ 6 ] and a major factor promoting MMP expression and activity is oxidative stress [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation

et al. 2022

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Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10-/- mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.

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“…Age-related macular degeneration (AMD) causes loss of central vision, which has significant impacts on quality of life. Plasma coQ10 levels are substantially reduced in patients with AMD, compared to control patients and this suggests an association between coQ10 and AMD pathogenesis [114]. Since the retina and the ocular macula are exposed to light more than any organ or tissue in the body, these districts will be particularly sensitive to oxidative stress and lipid peroxidation.…”

Section: Vitamin C and Coenzyme Q10mentioning

confidence: 99%

Potential Properties of Natural Nutraceuticals and Antioxidants in Eye Protection

Maiuolo¹,

Bulotta²,

Oppedisano³

et al. 2022

Preprint

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Eye health is crucial and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation of patients with natural antioxidants and nutraceuticals. In particular, evidence has been accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin, in particular, has been found to protect foto-receptors thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. On the other hand, CoQ10 has been demonstrated to produce consistent effect in reducing ocular pressure thereby leding to protection in patients undergoing glaucoma. Finally, both grape seed extract rich in anthocyanosides and polynsatured fatty acids (PUFAs) seem to contribute in the prevention of retinal disorders. Thus, combination of nutraceuticals and anti-oxidants may represent the right solution for a multiaction activity in eye protection to be associated to current drug therapies, and this will be of potential interest in early stages of eye disorders.

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Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Age Related Macular Degeneration, Role in Pathophysiology, and Possible New Therapeutic Strategies

Cited by 20 publications

References 205 publications

Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study

Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study

Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation

Potential Properties of Natural Nutraceuticals and Antioxidants in Eye Protection

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