PMID- 28499984
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20220129
IS  - 1872-8278 (Electronic)
IS  - 1567-7249 (Linking)
VI  - 36
DP  - 2017 Sep
TI  - Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma 
      and ocular hypertension: A case series.
PG  - 96-102
LID - S1567-7249(17)30126-5 [pii]
LID - 10.1016/j.mito.2017.05.003 [doi]
AB  - 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.
CI  - Copyright (c) 2017 Elsevier B.V. and Mitochondria Research Society. All rights 
      reserved.
FAU - Lascaratos, Gerassimos
AU  - Lascaratos G
AD  - NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust 
      and UCL Institute of Ophthalmology, London, UK. Electronic address: 
      glascaratos@gmail.com.
FAU - Chau, Kai-Yin
AU  - Chau KY
AD  - Department of Clinical Neurosciences, UCL Institute of Neurology, Royal Free 
      Hospital, London, UK.
FAU - Zhu, Haogang
AU  - Zhu H
AD  - Department of Optometry and Visual Science, City University, London, UK.
FAU - Gkotsi, Despoina
AU  - Gkotsi D
AD  - NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust 
      and UCL Institute of Ophthalmology, London, UK.
FAU - Kamal, Deborah
AU  - Kamal D
AD  - NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust 
      and UCL Institute of Ophthalmology, London, UK.
FAU - Gout, Ivan
AU  - Gout I
AD  - UCL Institute of Structural and Molecular Biology, London, UK.
FAU - Luthert, Philip J
AU  - Luthert PJ
AD  - Department of Pathology, UCL Institute of Ophthalmology, London, UK.
FAU - Schapira, Anthony H V
AU  - Schapira AHV
AD  - Department of Clinical Neurosciences, UCL Institute of Neurology, Royal Free 
      Hospital, London, UK.
FAU - Garway-Heath, David F
AU  - Garway-Heath DF
AD  - NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust 
      and UCL Institute of Ophthalmology, London, UK.
LA  - eng
GR  - 09-0787/AICR_/Worldwide Cancer Research/United Kingdom
PT  - Journal Article
DEP - 20170509
PL  - Netherlands
TA  - Mitochondrion
JT  - Mitochondrion
JID - 100968751
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Humans
MH  - Low Tension Glaucoma/*pathology
MH  - Middle Aged
MH  - Ocular Hypertension/*pathology
MH  - PTEN Phosphohydrolase/*analysis
MH  - Prospective Studies
MH  - Proto-Oncogene Proteins c-akt/*analysis
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*analysis
OTO - NOTNLM
OT  - 4EBP1
OT  - Akt1
OT  - Mitochondria
OT  - Normal tension glaucoma
OT  - Ocular hypertension
OT  - PTEN
OT  - S6K
OT  - mTOR
EDAT- 2017/05/14 06:00
MHDA- 2018/05/23 06:00
CRDT- 2017/05/14 06:00
PHST- 2016/07/29 00:00 [received]
PHST- 2017/03/07 00:00 [revised]
PHST- 2017/05/08 00:00 [accepted]
PHST- 2017/05/14 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2017/05/14 06:00 [entrez]
AID - S1567-7249(17)30126-5 [pii]
AID - 10.1016/j.mito.2017.05.003 [doi]
PST - ppublish
SO  - Mitochondrion. 2017 Sep;36:96-102. doi: 10.1016/j.mito.2017.05.003. Epub 2017 May 
      9.