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  • Mitophagy, Ferritinophagy and Ferroptosis in Retinal Pigment Epithelial Cells Under High Glucose Conditions: Implications for Diabetic Retinopathy and Age-Related Retinal Diseases.

Mitophagy, Ferritinophagy and Ferroptosis in Retinal Pigment Epithelial Cells Under High Glucose Conditions: Implications for Diabetic Retinopathy and Age-Related Retinal Diseases.

JOJ ophthalmology (2022-02-22)
Lalit Pukhrambam Singh, Thangal Yumnamcha, Takhellambam S Devi
摘要

Diabetic retinopathy (DR) is a devastating disease leading to blindness among majority of working adults around the globe. Nonetheless, an effective treatment or cure for the disease is still to be achieved. This is because the cellular and molecular mechanisms of DR are complex and not fully understood yet. In this article, we describe how high glucose induced TXNIP upregulation and associated redox stress may cause mitochondrial dysfunction, mitophagy, ferritinophagy (iron release by autophagy) and lysosome destabilization. Labile irons react with hydrogen peroxide (H2O2) to generate hydroxyl radicals (.OH) by the Fenton reaction and cause membrane phospholipid peroxidation due to reduction in glutathione (GSH) level and glutathione peroxidase 4 (GPX4) activity, which cause ferroptosis, a recently identified non-apoptotic cell death mechanism. We used in this study a retinal pigment epithelial cell line, ARPE- 19 and exposed it to high glucose in in vitro cultures to highlight some of the intricacies of these cellular processes, which may be relevant to the pathogenesis of DR and age-related retinal neurodegenerative diseases, such as age-related macular degeneration, AMD.

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Sigma-Aldrich
铁抑制剂-1, ≥95% (HPLC)
Sigma-Aldrich
抗-兔IgG(全分子)-过氧化物酶 山羊抗, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
齐留通, ≥98% (HPLC)
Sigma-Aldrich
抗小鼠IgG(全分子)-过氧化物酶 山羊抗, IgG fraction of antiserum, buffered aqueous solution