Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells
| Autor: | Sabina Honisch, Ellen Kilger, Marius Ueffing, Anke Jacob, Simon J. Clark, Vasiliki Panagiotakopoulou, Angela Armento, Michela Deleidi, Inga Sonntag |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Retinal pigment epithelium genetic structures Oxidative phosphorylation Biology medicine.disease_cause eye diseases Complement system Cell biology Pathogenesis 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Factor H 030221 ophthalmology & optometry medicine Glycolysis sense organs Homeostasis Oxidative stress 030304 developmental biology |
| DOI: | 10.1101/2020.01.08.898551 |
| Popis: | Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. About 50% of AMD patients present polymorphisms in the Complement Factor H (CFH) gene, coding for Factor H protein (FH). AMD-associated CFH risk variants, Y402H in particular, impair FH function leading to complement overactivation. In AMD, retinal homeostasis is compromised due to dysfunction of retinal pigment epithelium (RPE) cells. Whether FH contributes to AMD pathogenesis only via complement system dysregulation remains unclear. To investigate the potential role of FH on energy metabolism and oxidative stress in RPE cells, we silenced CFH in human hTERT-RPE1 cells. FH-deprived RPE cells exposed to oxidative insult, showed altered metabolic homeostasis, including reduction of glycolysis and mitochondrial respiration, paralleled by an increase in lipid peroxidation. Our data suggest that FH protects RPE cells from oxidative stress and metabolic reprogramming, highlighting a novel function for FH in AMD pathogenesis.Graphical abstract |
| Databáze: | OpenAIRE |
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