Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy

Yang, Xiongyi; Huang, Ze‐Xin; Xu, Mei; Chen, Yanxia; Cao, Mingzhe; Yi, Guoguo; Fu, Min

doi:10.1111/1753-0407.13373

Cited by 12 publications

(7 citation statements)

References 127 publications

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“…S2C ). Autophagy malfunction is known to be critically involved in the pathogenesis of DR, including the damage of the NVU ( Yang et al, 2023 ). Surprisingly, we did not detect any significant changes in autophagy-related genes in Müller cells.…”

Section: Resultsmentioning

confidence: 99%

IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

Augustine,

Pavlou,

Harkin

et al. 2023

Disease Models &Amp; Mechanisms

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Diabetic retinopathy (DR) is characterised by dysfunction of the retinal neurovascular unit, leading to visual impairment and blindness. Müller cells are key components of the retinal neurovascular unit and diabetes has a detrimental impact on these glial cells, triggering progressive neurovascular pathology of DR. Amongst many factors expressed by Müller cells, interleukin-33 (IL-33) has an established immunomodulatory role, and we investigated the role of endogenous IL-33 in DR. The expression of IL-33 in Müller cells increased during diabetes. Wild-type and Il33−/− mice developed equivalent levels of hyperglycaemia and weight loss following streptozotocin-induced diabetes. Electroretinogram a- and b-wave amplitudes, neuroretina thickness, and the numbers of cone photoreceptors and ganglion cells were significantly reduced in Il33−/− diabetic mice compared with those in wild-type counterparts. The Il33−/− diabetic retina also exhibited microglial activation, sustained gliosis, and upregulation of pro-inflammatory cytokines and neurotrophins. Primary Müller cells from Il33−/− mice expressed significantly lower levels of neurotransmitter-related genes (Glul and Slc1a3) and neurotrophin genes (Cntf, Lif, Igf1 and Ngf) under high-glucose conditions. Our results suggest that deletion of IL-33 promotes inflammation and neurodegeneration in DR, and that this cytokine is critical for regulation of glutamate metabolism, neurotransmitter recycling and neurotrophin secretion by Müller cells.

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Section: Resultsmentioning

confidence: 99%

IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

Augustine,

Pavlou,

Harkin

et al. 2023

Disease Models &Amp; Mechanisms

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“…In contrast to surgery alone or anti-VEGF therapy, herbal monomers for the treatment of DR have received extensive attention from academic researchers recently because of their mild side effects. [116,117] Overall, autophagy has clearly become a research hotspot for DR. [27,116] The majority of evidence indicates that autophagy plays a dual role in time and volume accumulation (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

“…Overall, autophagy has clearly become a research hotspot for DR. [ 27 , 116 ] The majority of evidence indicates that autophagy plays a dual role in time and volume accumulation (Fig. 4 ).…”

Section: Discussionmentioning

confidence: 99%

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Exploring the protective effects of herbal monomers against diabetic retinopathy based on the regulation of autophagy and apoptosis: A review

Hu,

Wang,

et al. 2023

Medicine

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Diabetic retinopathy (DR) has become one of the top 3 blinding eye diseases in the world. In spite of recent therapeutic breakthroughs, it is not yet possible to cure DR through pharmacotherapy. Cell death is thought to play a key role in the pathogenesis of DR. Moderate modulation of cellular autophagy and inhibition of apoptosis have been identified as effective targets for the treatment of DR. Numerous phytochemicals have emerged as potential new drugs for the treatment of DR. We collected basic DR research on herbal monomers through keywords such as autophagy and apoptosis, and conducted a systematic search for relevant research articles published in the PubMed database. This review provides the effects and reports of herbal monomers on various DR cellular and animal models in vivo and in vitro in the available literature, and emphasizes the importance of cellular autophagy and apoptosis as current DR therapeutic targets. Based on our review, we believe that herbal monomers that modulate autophagy and inhibit apoptosis may be potentially effective candidates for the development of new drugs in the treatment of DR. It provides a strategy for further development and application of herbal medicines for DR treatment.

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“… 9 For example, in the physiological state or at the early stage of some diseases, autophagy helps to clear senescent and damaged cells or organelles, while when autophagy is too strong, it has a pathogenic effect on cells, tissues, and organs. 10 Recently, many researches demonstrated that activating autophagy might be a promising therapeutic strategy in DR. 11 , 12 Adenosine monophosphate-activated protein kinase (AMPK) participates in the regulation of energy metabolism, plays a protective role in many diseases including DR. 13 Sirtuin 1 (SIRT1), one of the sirtuins family members, is a nicotinamide adenine dinucleotide (NAD +)-dependent histone deacetylase. SIRT1 is activated by the increase of intracellular adenosine monophosphate and NAD + levels.…”

Section: Introductionmentioning

confidence: 99%

Stachydrine Relieved the Inflammation and Promoted the Autophagy in Diabetes Retinopathy Through Activating the AMPK/SIRT1 Signaling Pathway

Yu,

Ke,

Zhou

et al. 2023

DMSO

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Background Diabetes retinopathy (DR) is a chronic, progressive, and potentially harmful retinal disease associated with persistent hyperglycemia. Autophagy is a lysosome-dependent degradation pathway that widely exists in eukaryotic cells, which has recently been demonstrated to participate in the DR development. Stachydrine (STA) is a water-soluble alkaloid extracted from Leonurus heterophyllus . This study aimed to explore the effects of STA on the autophagy in DR progression in vivo and in vitro. Methods High glucose-treated human retinal microvascular endothelial cells (HRMECs) and STA-treated rats were used to establish DR model. The reactive oxygen species (ROS) and inflammatory factor levels (TNF-α, IL-1β, and IL-6) were determined using corresponding kits. Additionally, the cell growth was analyzed using CCK-8 and EdU assays. Besides, LC3BII, p62, p-AMPKα, AMPKα, and SIRT1 protein levels were measured using Western blot. The LC3BII and SIRT1 expressions were also determined using immunofluorescence. Results The results showed that STZ decreased the ROS and inflammatory factor levels in the HG-treated HRMECs. Besides, after STA treatment, the beclin-1, LC3BII, p-AMPKα, and SIRT1 levels were increased, and p62 was decreased in the HG-treated HRMECs and the retinal tissue of STZ-treated rats. Conclusion In conclusion, this study demonstrated that STA effectively relieved the inflammation and promoted the autophagy in DR progression in vivo and in vitro through activating the AMPK/SIRT1 signaling pathway.

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Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy

Cited by 12 publications

References 127 publications

IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

Exploring the protective effects of herbal monomers against diabetic retinopathy based on the regulation of autophagy and apoptosis: A review

Stachydrine Relieved the Inflammation and Promoted the Autophagy in Diabetes Retinopathy Through Activating the AMPK/SIRT1 Signaling Pathway

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