Transketolase in human Müller cells is critical to resist light stress through the pentose phosphate and NRF2 pathways

Chen, Yingying; Zhang, Ting; Zeng, Shaoxue; Xu, Rong; Jin, Kaiyu; Coorey, Nathan J.; Wang, Yekai; Wang, Ke; Lee, Sora; Yam, Michelle; Zhu, Meidong; Chang, Andrew; Fan, Xiaohui; Zhang, Meixia; Du, Jianhai; Gillies, Mark C; Zhu, Ling

doi:10.1016/j.redox.2022.102379

Cited by 10 publications

(6 citation statements)

References 48 publications

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“…Similarly, Nrf2 also plays an essential role in the stress defence of Müller cells. “Nrf2-mediated oxidative stress response”, including an increase of Nrf2 and the sMAF family, is among the top cellular responses when Müller cells are exposed to strong light (a stress condition) compared to dim light (an unstressed condition) [ 67 ]. Nrf2 activation in Müller cells also rescues retinal ganglion cells (RGCs) from cell death [ 55 ], since Müller cells support other retinal neurons.…”

Section: Nrf2 Signalling In the Retinamentioning

confidence: 99%

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

Zhang

Zeng

et al. 2023

Biomedicines

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Age-related diseases, such as Parkinson’s disease, Alzheimer’s disease, cardiovascular diseases, cancers, and age-related macular disease, have become increasingly prominent as the population ages. Oxygen is essential for living organisms, but it may also cause disease when it is transformed into reactive oxygen species via biological processes in cells. Most of the production of ROS occurs in mitochondrial complexes I and III. The accumulation of ROS in cells causes oxidative stress, which plays a crucial role in human ageing and many diseases. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key antioxidant transcription factor that plays a central role in many diseases and ageing in general. It regulates many downstream antioxidative enzymes when cells are exposed to oxidative stress. A basic-region leucine zipper (bZIP) transcription factor, MAF, specifically the small MAF subfamily (sMAFs), forms heterodimers with Nrf2, which bind with Maf-recognition elements (MAREs) in response to oxidative stress. The role of this complex in the human retina remains unclear. This review summarises the current knowledge about Nrf2 and its downstream signalling, especially its cofactor—MAF, in ageing and diseases, with a focus on the retina. Since Nrf2 is the master regulator of redox homeostasis in cells, we hypothesise that targeting Nrf2 is a promising therapeutic approach for many age-related diseases.

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Section: Nrf2 Signalling In the Retinamentioning

confidence: 99%

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

Zhang

Zeng

et al. 2023

Biomedicines

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“…While typically these cofactors exist over-whelmingly in the reduced form in the cytosol, light exposure of cultured Müller glia has been shown to significantly increase the intracellular NADP + /NADPH ratio. 43 As such, the source of all- trans -retinal for RGR could derive from RDH-mediated oxidation of all- trans -retinol produced from bleaching of photoreceptors. 9 Notably, RDH11 is the most abundant RDH in human Müller glia, and its upregulation in the RGR+ subpopulation suggests that RDH11 could play an important role in supplying the substrate for RGR to facilitate photic visual pigment regeneration.…”

Section: Discussionmentioning

confidence: 99%

Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Müller glia

et al. 2023

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“… 43 Transketolase, the critical enzyme in the pentose phosphate pathway, was found to play a critical protective role on endoplasmic reticulum stress responses and cell survival in stressed human retina. 44 Although many studies have suggested that PCV is a special subtype of nAMD, there are still some differences in pathological mechanism between PCV and nAMD. In 2021, Van Dijk summarized three clinical subtypes of PCV: (1) PCV which is more closely related to nAMD; (2) PCV which is more closely related to BVN; and (3) PCV which is more closely related to polyp-like lesions.…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

Liu,

Sun,

Yang

et al. 2023

JIR

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Background Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV. Methods Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis. Results A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls. Conclusion This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.

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Transketolase in human Müller cells is critical to resist light stress through the pentose phosphate and NRF2 pathways

Cited by 10 publications

References 48 publications

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases

Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Müller glia

Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

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