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Determination of Mitochondrial Respiration and Glycolysis in Ex Vivo Retinal Tissue Samples
Published on: August 4, 2021
Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy
Carla Giordano1, Monica Montopoli, Elena Perli
1Dipartimento di Medicina Sperimentale e Patologia, Sapienza, Universita` di Roma, 00161 Rome, Italy.
Brain : a Journal of Neurology
|October 15, 2010
Summary
This study reveals that estrogen treatment can counteract the cellular damage and metabolic dysfunction in Leber's hereditary optic neuropathy (LHON) cells. These findings suggest a potential therapeutic strategy for this mitochondrial disease, explaining its higher prevalence in males.
Area of Science:
- Mitochondrial genetics and disease
- Cellular metabolism and bioenergetics
- Neurobiology and ophthalmology
Background:
- Leber's hereditary optic neuropathy (LHON) is a frequent mitochondrial DNA disease affecting retinal ganglion cells, predominantly in young males.
- The higher prevalence in males remains unexplained, prompting investigation into potential sex-specific protective mechanisms.
- Mitochondrial dysfunction, including Complex I mutations, leads to oxidative stress and cell death in LHON.
Purpose of the Study:
- To investigate the role of oestrogens in mitigating the effects of LHON-associated mitochondrial dysfunction.
- To explore the potential of oestrogen-based therapies for LHON.
- To understand the metabolic basis for the male predominance in LHON.
Main Methods:
- Utilized LHON osteosarcoma-derived cybrids with specific mitochondrial DNA mutations (11778/ND4, 3460/ND1, 14484/ND6).
- Cultured cells in glucose or galactose medium to induce metabolic stress.
- Administered 17β-oestradiol and an oestrogen receptor antagonist (ICI 182780) to assess treatment effects.
- Analyzed reactive oxygen species production, mitochondrial membrane potential, apoptosis, cell viability, and mitochondrial morphology.
Main Results:
- LHON cybrids in galactose medium exhibited increased oxidative stress, reduced mitochondrial potential, higher apoptosis, and impaired cell viability.
- 17β-oestradiol treatment significantly reversed these pathological changes, activating superoxide dismutase 2 and promoting mitochondrial biogenesis.
- Oestrogen receptor mediation was confirmed, with estrogen receptor β found in the mitochondria of retinal ganglion cells.
Conclusions:
- Oestrogen receptor-mediated effects of 17β-oestradiol can rescue mitochondrial dysfunction in LHON cybrids.
- These findings provide a metabolic explanation for the male prevalence in LHON.
- Oestrogen-like molecules show promise as a potential therapeutic strategy for Leber's hereditary optic neuropathy.
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