Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

Ouyang, Junlin; Zhou, Ling; Wang, Qing

doi:10.3389/fendo.2023.1234824

Cited by 11 publications

(1 citation statement)

References 123 publications

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“…The onset of diabetic retinopathy (DR) typically takes approximately 10 years after the diagnosis of diabetes for clinical manifestations to emerge, with an incidence rate ranging from 24.7% to 35.7%. 1 Microvascular complications of diabetes frequently occur in patients with DR, which is rapidly increasing globally. 2 DR consists of non-proliferative DR and proliferative DR, according to whether neovascularization occurs in retina.…”

Section: Introductionmentioning

confidence: 99%

APAF1 Silencing Ameliorates Diabetic Retinopathy by Suppressing Inflammation, Oxidative Stress, and Caspase-3/GSDME-Dependent Pyroptosis

Ding,

Chen,

et al. 2024

DMSO

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Objective Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR. Methods Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells. Results Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1β, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells. Conclusion APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis.

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Section: Introductionmentioning

confidence: 99%

APAF1 Silencing Ameliorates Diabetic Retinopathy by Suppressing Inflammation, Oxidative Stress, and Caspase-3/GSDME-Dependent Pyroptosis

Ding,

Chen,

et al. 2024

DMSO

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Melanin‐Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age‐Related Macular Degeneration

Huang,

Deng,

Wang

et al. 2024

Adv Healthcare Materials

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Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis and subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age‐related macular degeneration (dAMD), causing irreversible vision loss in the global elderly population. However, currently, no effective interventional treatment strategy exists in clinical practice. Herein, lesion site‐targeted melanin‐like nanoparticles, named ConA‐MelNPs, are designed as a novel ferroptosis inhibitor for retinal degenerative diseases. ConA‐MelNPs possessed chelating iron ion characteristics, alleviating severe mitochondrial damage caused by oxidative stress and protecting RPE cells from ferroptosis induced by sodium iodate (NaIO3). In a preclinical dAMD mouse model, a single intravitreal injection of ConA‐MelNPs yielded significant responses in electroretinograms and visually‐driven optomotor responses in visually impaired mice, resisting the challenge posed by secondary NaIO3‐induced injuries, with the long‐term sustainability of its therapeutic effect. Mechanistically, ConA‐MelNPs achieve a therapeutic effect by interrupting the detrimental cascade involving “RPE cell ferroptosis, lethal oxidative stress, and microglial proinflammatory activation,” affording the restoration of retinal homeostasis. The synthesized ConA‐MelNPs demonstrated good biosafety, with no detected ophthalmic or systemic side effects. Collectively, ConA‐MelNPs are proposed as a promising therapeutic option for atrophic retinal diseases such as dAMD.

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Analyzing the role of ferroptosis in ribosome‐related bone marrow failure disorders: From pathophysiology to potential pharmacological exploitation

Papadimitriou‐Tsantarliotou,

Avgeros,

Konstantinidou

et al. 2024

IUBMB Life

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Within the last decade, the scientific community has witnessed the importance of ferroptosis as a novel cascade of molecular events leading to cellular decisions of death distinct from apoptosis and other known forms of cell death. Notably, such non‐ apoptotic and iron‐dependent regulated cell death has been found to be intricately linked to several physiological processes as well as to the pathogenesis of various diseases. To this end, recent data support the notion that a potential molecular connection between ferroptosis and inherited bone marrow failure (IBMF) in individuals with ribosomopathies may exist. In this review, we suggest that in ribosome‐related IBMFs the identified mutations in ribosomal proteins lead to changes in the ribosome composition of the hematopoietic progenitors, changes that seem to affect ribosomal function, thus enhancing the expression of some mRNAs subgroups while reducing the expression of others. These events lead to an imbalance inside the cell as some molecular pathways are promoted while others are inhibited. This disturbance is accompanied by ROS production and lipid peroxidation, while an additional finding in most of them is iron accumulation. Once lipid peroxidation and iron accumulation are the two main characteristics of ferroptosis, it is possible that this mechanism plays a key role in the manifestation of IBMF in this type of disease. If this molecular mechanism is further confirmed, new pharmacological targets such as ferroptosis inhibitors that are already exploited for the treatment of other diseases, could be utilized to improve the treatment of ribosomopathies.

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Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

Cited by 11 publications

References 123 publications

APAF1 Silencing Ameliorates Diabetic Retinopathy by Suppressing Inflammation, Oxidative Stress, and Caspase-3/GSDME-Dependent Pyroptosis

APAF1 Silencing Ameliorates Diabetic Retinopathy by Suppressing Inflammation, Oxidative Stress, and Caspase-3/GSDME-Dependent Pyroptosis

Melanin‐Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age‐Related Macular Degeneration

Analyzing the role of ferroptosis in ribosome‐related bone marrow failure disorders: From pathophysiology to potential pharmacological exploitation

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