Hydrogen peroxide modulates energy metabolism and oxidative stress in cultures of permanent human Müller cells MIO‐M1

Peters, Sven; Griebsch, Max; Klemm, Matthias; Haueisen, Jens; Hammer, Martin

doi:10.1002/jbio.201600201

Cited by 7 publications

(5 citation statements)

References 50 publications

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“…This assumption was further confirmed with ATP measurements 6 h after BL exposure demonstrating only a slight loss of ATP ( Figure S3 ). This is in accordance with the study of H 2 O 2 -incubated primary rat MCs, displaying an increased number of floating and apoptotic MCs [ 56 ]. BL exposure of MCs also led to enhanced expression of numerous pro-apoptotic proteins in a screen for apoptotic proteins ( Figure S2 ), underlining apoptosis as the primary cell death pathway.…”

Section: Discussionsupporting

confidence: 92%

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Out of the Shadow: Blue Light Exposure Induces Apoptosis in Müller Cells

Fietz

Hurst

Schnichels

2022

IJMS

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Awareness toward the risks of blue light (BL) exposure is rising due to increased use of BL-enriched LEDs in displays. Short-wave BL (400–500 nm) has a high photochemical energy, leading to the enhanced production of reactive oxygen species (ROS). BL potentially plays a role in causing dry eye, cataracts, and age-related macular degeneration (AMD). The effect of BL on retinal pigment epithelium cells (RPEs) or photoreceptors has been extensively investigated. In contrast, only a few studies have investigated the effects of BL exposure on Müller cells (MCs). This is mainly due to their lack of photosensitive elements and the common assumption that their reaction to stress is only secondary in disease development. However, MCs perform important supportive, secretory, and immune functions in the retina, making them essential for retinal survival. Increased oxidative stress is a key player in many retinal diseases such as AMD or glaucoma. We hypothesize that increased oxidative stress can also affect MCs. Thus, we simulated oxidative stress levels by exposing primary porcine MCs and human MIO-M1 cells to BL. To confirm the wavelength-specificity, the cells were further exposed to red (RL), purple (PL), and white light (WL). BL and WL exposure increased ROS levels, but only BL exposure led to apoptosis in primary MCs. Thus, BL accounted for the harmful part of WL exposure. When cells were simultaneously exposed to BL and RL (i.e., PL), cell damage due to BL could be partly prevented, as could the inhibition of p53, demonstrating the protective effect of RL and p53 dependency. In contrast, BL hardly induced apoptosis in MIO-M1 cells, which is likely due to the immortalization of the cells. Therefore, enhanced oxidative stress levels can significantly harm MC function, probably leading to decreased retinal survival and, thus, further enhancing the progression of retinal diseases. Preventing the cell death of these essential retinal cells represents a promising therapy option to enhance retinal survival.

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Section: Discussionsupporting

confidence: 92%

“…Regarding BL-induced apoptosis in MC, this blockade may be caused by a p53 mutation. Nevertheless, enhanced oxidative stress levels ( Figure S1B ) could result in an impairment of MIO-M1 function, despite the preserved viability, as seen in starved and H 2 O 2 -exposed MIO-M1 cells [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Out of the Shadow: Blue Light Exposure Induces Apoptosis in Müller Cells

Fietz

Hurst

Schnichels

2022

IJMS

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“…Similarly to our results, Peters et al . 68 found a H 2 O 2 -induced hyperpolarization of the MMP under low concentrations and treatment periods for which changes in cell viability were not detected.…”

Section: Discussionmentioning

confidence: 89%

Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress

Menges

Minakaki

Schaefer

et al. 2017

Sci Rep

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Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson’s disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H2O2 or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed “mitospheres”. Mitosphere formation mechanistically depended on the fission factor Drp1, and was paralleled by reduced mitochondrial fusion. Furthermore, mitospheres were linked to a decrease in mitochondrial activity, and preceded Caspase3 activation. Even though fragmentation of dysfunctional mitochondria is considered to be a prerequisite for mitochondrial degradation, mitospheres were not degraded via Parkin-mediated mitophagy. Importantly, we provide compelling evidence that aSyn prevents mitosphere formation and reduces apoptosis under OS. In contrast, aSyn did not protect against Rotenone, which led to a different, previously described donut-shaped mitochondrial morphology. Our findings reveal a dichotomic role of aSyn in mitochondrial biology, which is linked to distinct types of stress-induced mitochondrial fragmentation. Specifically, aSyn may be part of a cellular defense mechanism preserving neural mitochondrial homeostasis in the presence of increased OS levels, while not protecting against stressors directly affecting mitochondrial function.

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“…Although this is an established method for analysis of the FLIM data, such an averaging of the fluorescence lifetimes across the cell may result in the loss of some information on metabolism. Therefore, more advanced approaches based on segmentation of mitochondria have been developed [17,18]. However, for this specific study conventional analysis delivers enough information to make the relevant conclusions.…”

Section: Discussionmentioning

confidence: 99%

Interrogation of tumor metabolism in tissue samplesex vivousing fluorescence lifetime imaging of NAD(P)H

Lukina

Shimolina

Kiselev

et al. 2019

Methods Appl. Fluoresc.

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Exploring metabolism in human tumors at the cellular level remains a challenge. The reduced form of metabolic cofactor NAD(P)H is one of the major intrinsic fluorescent components in tissues and a valuable indicator of cellular metabolic activity. Fluorescence lifetime imaging (FLIM) enables resolution of both the free and protein-bound fractions of this cofactor, and thus, high sensitivity detection of relative changes in the NAD(P)H-dependent metabolic pathways in real time. However, the clinical use of this technique is still very limited. The applications of metabolic FLIM could be usefully expanded by probing cellular metabolism in tissues ex vivo. For this, however, the development of appropriate tissue preservation protocols is required in order to maintain the optical metabolic characteristics in the ex vivo sample in a state similar to those of the tumor in vivo. Using mouse tumor models of different histological types—colorectal cancer, lung carcinoma and melanoma—we tested eight different methods of tissue handling by comparing NAD(P)H fluorescence decay parameters ex vivo and in vivo as measured with two-photon excited FLIM microscopy. It was found that the samples placed in 10% BSA on ice immediately after excision maintained the same fluorescence lifetimes and free/bound ratios as measured in vivo for at least 3 hours. This protocol was subsequently used for metabolic assessments in fresh postoperative samples from colorectal cancer patients. A high degree of inter- and intra-tumor heterogeneity with a trend to a more oxidative metabolism was detected in T3 colorectal tumors in comparison with normal tumor-distant colon samples. These results suggest that the methodology developed on the basis of FLIM of NAD(P)H in tissues ex vivo show promise for interrogating the metabolic state of patients’ tumors.

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Hydrogen peroxide modulates energy metabolism and oxidative stress in cultures of permanent human Müller cells MIO‐M1

Cited by 7 publications

References 50 publications

Out of the Shadow: Blue Light Exposure Induces Apoptosis in Müller Cells

Out of the Shadow: Blue Light Exposure Induces Apoptosis in Müller Cells

Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress

Interrogation of tumor metabolism in tissue samplesex vivousing fluorescence lifetime imaging of NAD(P)H

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