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Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma and ocular hypertension: A case series

Lascaratos, G; Chau, K-Y; Zhu, H; Gkotsi, D; Kamal, D; Gout, I; Luthert, PJ; ... Garway-Heath, DF; + view all (2017) Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma and ocular hypertension: A case series. Mitochondrion , 36 pp. 96-102. 10.1016/j.mito.2017.05.003. Green open access

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Abstract

Glaucoma is the most common optic neuropathy in humans and the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP), while increasing evidence suggests that systemic mitochondrial abnormalities may also be implicated in its pathogenesis. We have recently shown that patients who have not developed glaucoma despite being exposed for many years to high IOP (ocular hypertension - OHT) have more efficient mitochondria, measured in peripheral blood lymphocytes, when compared to age-similar controls and fast progressing normal tension glaucoma (NTG) patients. In this prospective case series we aimed to explore some of the molecular pathways involved in mitochondrial efficiency in glaucoma resistance by measuring the systemic activity (in peripheral blood) of key mitochondrial regulators: the mammalian target of rapamycin (mTOR) and its major upstream regulators and downstream effectors that form the PTEN-Akt1-mTOR signalling pathway. We found no statistically significant difference in the systemic mTOR activity between the three groups (control, NTG and OHT). In line with the mTOR results, there was no significant difference in the activity of both the two major upstream mTOR regulators (PTEN and Akt1) and its two main downstream effectors (S6K and 4EBP1). In a single NTG patient, with history of Raynaud's, significantly higher mTOR activity was noted. We conclude that the PTEN-Akt1-mTOR pathway does not appear to play a central role in mitochondrial efficiency in OHT.

Type: Article
Title: Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma and ocular hypertension: A case series
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.mito.2017.05.003
Publisher version: http://doi.org/10.1016/j.mito.2017.05.003
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: 4EBP1, Akt1, Mitochondria, Normal tension glaucoma, Ocular hypertension, PTEN, S6K, mTOR
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1558031
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