Mitochondrial function in Müller cells - Does it matter?

Toft‐Kehler, Anne Katrine; Skytt, Dorte M.; Svare, Alicia; Lefevere, Evy; Hove, Inge Van; Moons, Lieve; Waagepetersen, Helle S.; Kolko, Miriam

doi:10.1016/j.mito.2017.02.002

Cited by 52 publications

(39 citation statements)

References 97 publications

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“…Swelling, vacuolization, and necrosis of Müller cells are characteristic features of hepatic retinopathy [ 26 ]. Müller cells have a central role in the survival of photoreceptors and neurons, modulate the immune response in the retina, and stabilize the structure of the retinal tissue [ 27 ]. Thus, Müller cells have been considered potential therapeutic targets to inhibit these retinal degenerative diseases [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Aloin Inhibits Müller Cells Swelling in a Rat Model of Thioacetamide-Induced Hepatic Retinopathy

Jung

Kim

2018

Molecules

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Swelling of retinal Müller cells is implicated in retinal edema and neuronal degeneration. Müller cell swelling is observed in patients with liver failure and is referred to as hepatic retinopathy. In the present study, we evaluated the effects of aloin, an anthraquinone-C-glycoside present in various Aloe species, on Müller cell dysfunction in a rat model of thioacetamide (TAA)-induced hepatic retinopathy. Experimental hepatic retinopathy was induced by three injections of TAA (200 mg/kg/day, intraperitoneal injection) for 3 days in rats. After the last injection of TAA, aloin (50 and 100 mg/kg) was orally gavaged for 5 days. The effects of aloin on the liver injury, serum ammonia levels, Müller cell swelling, glial fibrillary acidic protein (GFAP) expression, and gene expression of Kir4.1 and aquaporin-4 were examined. TAA-injected rats exhibited liver failure and hyperammonemia. In the TAA-injected rats, Müller cell bodies were highly enlarged, and GFAP, an indicator of retinal stress, was highly expressed in the retinas, indicating a predominant Müller cell gliosis. However, administration of aloin suppressed liver injury as well as Müller cell swelling through the normalization of Kir4.1 and aquaporin-4 channels, which play a key role in potassium and water transport in Müller cells. These results indicate that aloin may be helpful to protect retinal injury associated with liver failure.

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Section: Discussionmentioning

confidence: 99%

Aloin Inhibits Müller Cells Swelling in a Rat Model of Thioacetamide-Induced Hepatic Retinopathy

Jung

Kim

2018

Molecules

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“…Müller cells rely primarily on glycolysis and are rich in glycogen reserves [ 85 , 86 ]. Although glucose is their preferred substrate, Müller cells also utilize extracellular glutamate [ 87 ], and for this reason are believed to play a role in preventing glutamate excitotoxicity. Cell culture experiments have confirmed that Müller cells exhibit aerobic glycolysis and provide lactate that can be transferred to retinal neurons for metabolic support [ 88 ].…”

Section: Retinal Bioenergetics and Mitochondrial Substrate Selectimentioning

confidence: 99%

Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease

2020

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Diabetic retinopathy (DR), a common chronic complication of diabetes mellitus and the leading cause of vision loss in the working-age population, is clinically defined as a microvascular disease that involves damage of the retinal capillaries with secondary visual impairment. While its clinical diagnosis is based on vascular pathology, DR is associated with early abnormalities in the electroretinogram, indicating alterations of the neural retina and impaired visual signaling. The pathogenesis of DR is complex and likely involves the simultaneous dysregulation of multiple metabolic and signaling pathways through the retinal neurovascular unit. There is evidence that microvascular disease in DR is caused in part by altered energetic metabolism in the neural retina and specifically from signals originating in the photoreceptors. In this review, we discuss the main pathogenic mechanisms that link alterations in neural retina bioenergetics with vascular regression in DR. We focus specifically on the recent developments related to alterations in mitochondrial metabolism including energetic substrate selection, mitochondrial function, oxidation-reduction (redox) imbalance, and oxidative stress, and critically discuss the mechanisms of these changes and their consequences on retinal function. We also acknowledge implications for emerging therapeutic approaches and future research directions to find novel mitochondria-targeted therapeutic strategies to correct bioenergetics in diabetes. We conclude that retinal bioenergetics is affected in the early stages of diabetes with consequences beyond changes in ATP content, and that maintaining mitochondrial integrity may alleviate retinal disease.

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“…Recent studies have proposed a potential role of impaired energy availability, uptake and utilization in glaucoma (Toft‐Kehler et al. , ; Coughlin et al. ; Kleesattel et al.…”

Section: Introductionmentioning

confidence: 99%

Potential metabolic markers in glaucoma and their regulation in response to hypoxia

Vohra

Dalgaard

Vibæk

et al. 2019

Acta Ophthalmologica

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Purpose: To assess novel differences in serum levels of glucose, lactate and amino acids in patients with normal-tension glaucoma (NTG) compared to agematched controls, at baseline and in response to universal hypoxia. Methods: Twelve patients diagnosed with NTG and eleven control subjects underwent normobaric hypoxia for 2 hr. Peripheral venous blood samples were taken at baseline, during hypoxia and in the recovery phase. Serum glucose and lactate levels were measured by a blood gas analyser. Amino acids were analysed by high-performance liquid chromatography. Results: Baseline levels of lactate and total amino acids were significantly lower in patients with NTG compared to healthy controls. No differences were seen in blood glucose levels between the two groups. Lactate levels remained unchanged during hypoxia in the control group, but increased in patients with NTG. In the recovery phase, total amino acid levels were reduced in the control group, whereas no changes were found in patients with NTG. Conclusion: Reduced serum levels of lactate and total amino acids were identified as potential markers for NTG. Moreover, significant differential regulatory patterns of certain amino acids were found in patients with NTG compared to control subjects. Overall, our results suggest a link between systemic energy metabolites and NTG and support a novel understanding of glaucoma as an inner retinal manifestation of a systemic condition.

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Mitochondrial function in Müller cells - Does it matter?

Cited by 52 publications

References 97 publications

Aloin Inhibits Müller Cells Swelling in a Rat Model of Thioacetamide-Induced Hepatic Retinopathy

Aloin Inhibits Müller Cells Swelling in a Rat Model of Thioacetamide-Induced Hepatic Retinopathy

Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease

Potential metabolic markers in glaucoma and their regulation in response to hypoxia

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