Impaired mitochondrial dynamics and removal of the damaged mitochondria in diabetic retinopathy

Alka, Kumari; Kumar, J.; Kowluru, Renu A.

doi:10.3389/fendo.2023.1160155

Cited by 11 publications

(5 citation statements)

References 55 publications

(90 reference statements)

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“…These changes in diabetic patients and mice, which correlated with increased FIS1 and DRP1 levels, respectively [209,211], were also observed in aortic ECs cultured under hyperglycemic conditions [209]. Diabetic retinopathy is also associated with disturbed mitochondrial dynamics in human retinal ECs, where the acetylation of MFN2 protein plays a role [212]. However, hyperglycemia also affects other mitochondrial aspects, such as mtDNA repair mechanisms, which are impaired in hyperglycemia.…”

Section: Endothelial Mitochondrial Dysfunction In Diabetes Mellitusmentioning

confidence: 80%

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Kulovic-Sissawo,

Tocantins,

Diniz

et al. 2024

Biology

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Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative diseases, and it contributes significantly to the global health burden. Recent research indicates a link between cardiovascular risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, and endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are recruited into the vessel wall to maintain appropriate endothelial function, repair, and angiogenesis. After attachment, EPCs differentiate into mature endothelial cells (ECs). Like ECs, EPCs are also susceptible to CVRFs, including metabolic dysfunction and chronic inflammation. Therefore, mitochondrial dysfunction of EPCs may have long-term effects on the function of the mature ECs into which EPCs differentiate, particularly in the presence of endothelial damage. However, a link between CVRFs and impaired mitochondrial function in EPCs has hardly been investigated. In this review, we aim to consolidate existing knowledge on the development of mitochondrial and endothelial dysfunction in the vascular endothelium, place it in the context of recent studies investigating the consequences of CVRFs on EPCs, and discuss the role of mitochondrial dysfunction. Thus, we aim to gain a comprehensive understanding of mechanisms involved in EPC deterioration in relation to CVRFs and address potential therapeutic interventions targeting mitochondrial health to promote endothelial function.

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Section: Endothelial Mitochondrial Dysfunction In Diabetes Mellitusmentioning

confidence: 80%

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Kulovic-Sissawo,

Tocantins,

Diniz

et al. 2024

Biology

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“…Acetylphosphate, as a marker of mitochondrial activity, is considered a metabolic intermediate in the generation of citric acid cycle precursors and often mediates nonenzymatic acetylation ( 57 ). Previous studies revealed that acetylation of proteins such as mitofusin 2 ( 58 ), histones ( 59 ), and P65 ( 60 ) contributes to the development of DR. Our study suggested that acetylphosphate may be a risk factor for DR and the acetylation it mediates holds promise as a potential focus for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study

Yang,

Ma,

Yao

et al. 2024

Front. Endocrinol.

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BackgroundDiabetic retinopathy (DR) is a microvascular complication of diabetes, severely affecting patients’ vision and even leading to blindness. The development of DR is influenced by metabolic disturbance and genetic factors, including gene polymorphisms. The research aimed to uncover the causal relationships between blood metabolites and DR.MethodsThe two-sample mendelian randomization (MR) analysis was employed to estimate the causality of blood metabolites on DR. The genetic variables for exposure were obtained from the genome-wide association study (GWAS) dataset of 486 blood metabolites, while the genetic predictors for outcomes including all-stage DR (All DR), non-proliferative DR (NPDR) and proliferative DR (PDR) were derived from the FinnGen database. The primary analysis employed inverse variance weighted (IVW) method, and supplementary analyses were performed using MR-Egger, weighted median (WM), simple mode and weighted mode methods. Additionally, MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were also conducted to guarantee the accuracy and robustness of the results. Subsequently, we replicated the MR analysis using three additional datasets from the FinnGen database and conducted a meta-analysis to determine blood metabolites associated with DR. Finally, reverse MR analysis and metabolic pathway analysis were performed.ResultsThe study identified 13 blood metabolites associated with All DR, 9 blood metabolites associated with NPDR and 12 blood metabolites associated with PDR. In summary, a total of 21 blood metabolites were identified as having potential causal relationships with DR. Additionally, we identified 4 metabolic pathways that are related to DR.ConclusionThe research revealed a number of blood metabolites and metabolic pathways that are causally associated with DR, which holds significant importance for screening and prevention of DR. However, it is noteworthy that these causal relationships should be validated in larger cohorts and experiments.

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“…Mitochondrial dysfunction is linked to various ocular diseases, including autosomal dominant optic atrophy [85], Leber's hereditary optic neuropathy [86], glaucoma [87], age-related macular degeneration (AMD) [88], and diabetic retinopathy (DR) [89]. It is known that inflammation can be triggered by oxidative stress caused by mitochondrial damage [90].…”

Section: Discussionmentioning

confidence: 99%

Mitophagy in Astrocytes Is Required for the Health of Optic Nerve

Yazdankhah,

Ghosh,

Liu

et al. 2023

Cells

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Mitochondrial dysfunction in astrocytes has been implicated in the development of various neurological disorders. Mitophagy, mitochondrial autophagy, is required for proper mitochondrial function by preventing the accumulation of damaged mitochondria. The importance of mitophagy, specifically in the astrocytes of the optic nerve (ON), has been little studied. We introduce an animal model in which two separate mutations act synergistically to produce severe ON degeneration. The first mutation is in Cryba1, which encodes βA3/A1-crystallin, a lens protein also expressed in astrocytes, where it regulates lysosomal pH. The second mutation is in Bckdk, which encodes branched-chain ketoacid dehydrogenase kinase, which is ubiquitously expressed in the mitochondrial matrix and involved in the catabolism of the branched-chain amino acids. BCKDK is essential for mitochondrial function and the amelioration of oxidative stress. Neither of the mutations in isolation has a significant effect on the ON, but animals homozygous for both mutations (DM) exhibit very serious ON degeneration. ON astrocytes from these double-mutant (DM) animals have lysosomal defects, including impaired mitophagy, and dysfunctional mitochondria. Urolithin A can rescue the mitophagy impairment in DM astrocytes and reduce ON degeneration. These data demonstrate that efficient mitophagy in astrocytes is required for ON health and functional integrity.

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Impaired mitochondrial dynamics and removal of the damaged mitochondria in diabetic retinopathy

Cited by 11 publications

References 55 publications

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study

Mitophagy in Astrocytes Is Required for the Health of Optic Nerve

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