Projects per year
Abstract
The recovery of mitochondrial quality control (MQC) may bring innovative solutions for neuroprotection, while imposing a significant challenge given the need of holistic approaches to restore mitochondrial dynamics (fusion/fission) and turnover (mitophagy and biogenesis). In diabetic retinopathy, this is compounded by our lack of understanding of human retinal neurodegeneration, but also how MQC processes interact during disease progression. Here, we show that mitochondria hyperfusion is characteristic of retinal neurodegeneration in human and murine diabetes, blunting the homeostatic turnover of mitochondria and causing metabolic and neuro-inflammatory stress. By mimicking this mitochondrial remodelling in vitro, we ascertain that N6-furfuryladenosine enhances mitochondrial turnover and bioenergetics by relaxing hyperfusion in a controlled fashion. Oral administration of N6-furfuryladenosine enhances mitochondrial turnover in the diabetic mouse retina (Ins2Akita males), improving clinical correlates and conferring neuroprotection regardless of glycaemic status. Our findings provide translational insights for neuroprotection in the diabetic retina through the holistic recovery of MQC.
Original language | English |
---|---|
Article number | 1124 |
Number of pages | 16 |
Journal | Nature Communications |
Volume | 15 |
Issue number | 1 |
DOIs | |
Publication status | Published - 6 Feb 2024 |
Bibliographical note
Acknowledgments:This work was supported by Diabetes UK (20/0006296) to JRH, EFSD/Boehringer Ingelheim Grant to JRH, Fight for Sight (1842/1843) to JRH, Wellcome Trust (213458/Z/18/Z) to JRH and Medical Research Council, UK (MC_UU_00018/2) to IGG. Special thanks to Professor Astrid Limb (University College London) for providing the MIO-M1 cell line. Cartoon in Fig. 3a was created with BioRender.com. We thank the eye donors for their inestimable contribution to diabetes research.
Fingerprint
Dive into the research topics of 'Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status'. Together they form a unique fingerprint.Projects
- 1 Finished
-
Rescuing mitochondrial self-repair for the management of diabetic retinopathy
Wallace, G. (Co-Investigator), Romero, J. (Principal Investigator), Rauz, S. (Co-Investigator) & Barnes, N. (Co-Investigator)
10/01/22 → 9/01/25
Project: Research