PMID- 29803556
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20221214
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 174
DP  - 2018 Sep
TI  - Circular RNAs profiling in the cystathionine-beta-synthase mutant mouse reveals 
      novel gene targets for hyperhomocysteinemia induced ocular disorders.
PG  - 80-92
LID - S0014-4835(18)30244-6 [pii]
LID - 10.1016/j.exer.2018.05.026 [doi]
AB  - Cystathionine-beta-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes 
      beta-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5'-phosphate 
      helps to form cystathionine which in turn is converted to cysteine. CBS resides 
      at the intersection of transmethylation, transsulfuration, and remethylation 
      pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential 
      step in glutathione synthesis. Redox homeostasis, free-radical detoxification and 
      one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its 
      deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular 
      thromboembolism and eye-lens dislocation along with vascular cognitive impairment 
      and dementia. HHcy results in retinovascular, coronary, cerebral and peripheral 
      vessels' dysfunction and how it causes metabolic dysregulation predisposing 
      patients to serious eye conditions remains unknown. HHcy orchestrates 
      inflammation and redox imbalance via epigenetic remodeling leading to 
      neurovascular pathologies. Although circular RNAs (circRNAs) are dominant players 
      regulating their parental genes' expression dynamics, their importance in ocular 
      biology has not been appreciated. Progress in gene-centered analytics via 
      improved microarray and bioinformatics are enabling dissection of genomic 
      pathways however there is an acute under-representation of circular RNAs in 
      ocular disorders. This study undertook circRNAs' analysis in the eyes of CBS 
      deficient mice identifying a pool of 12532 circRNAs, 74 exhibited differential 
      expression profile, ( approximately )27% were down-regulated while most were up-regulated 
      (( approximately )73%). Findings also revealed several microRNAs that are specific to each 
      circRNA suggesting their roles in HHcy induced ocular disorders. Further analysis 
      of circRNAs helped identify novel parental genes that seem to influence certain 
      eye disease phenotypes.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Singh, Mahavir
AU  - Singh M
AD  - Eye and Vision Science Laboratory, Department of Physiology, University of 
      Louisville School of Medicine, Louisville, KY 40202, USA; Department of 
      Physiology, University of Louisville School of Medicine, Louisville, KY 40202, 
      USA. Electronic address: mahavir.singh@louisville.edu.
FAU - George, Akash K
AU  - George AK
AD  - Eye and Vision Science Laboratory, Department of Physiology, University of 
      Louisville School of Medicine, Louisville, KY 40202, USA; Department of 
      Physiology, University of Louisville School of Medicine, Louisville, KY 40202, 
      USA.
FAU - Homme, Rubens Petit
AU  - Homme RP
AD  - Eye and Vision Science Laboratory, Department of Physiology, University of 
      Louisville School of Medicine, Louisville, KY 40202, USA; Department of 
      Physiology, University of Louisville School of Medicine, Louisville, KY 40202, 
      USA.
FAU - Majumder, Avisek
AU  - Majumder A
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
FAU - Laha, Anwesha
AU  - Laha A
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
FAU - Sandhu, Harpal S
AU  - Sandhu HS
AD  - Department of Ophthalmology and Visual Sciences, University of Louisville School 
      of Medicine, Louisville, KY 40202, USA; Kentucky Lions Eye Center, University of 
      Louisville School of Medicine, Louisville, KY 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, KY 40202, USA.
LA  - eng
GR  - R01 AR071789/AR/NIAMS NIH HHS/United States
GR  - R01 DK104653/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180525
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (RNA, Circular)
RN  - 63231-63-0 (RNA)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Cystathionine beta-Synthase/*genetics/metabolism
MH  - Epigenomics
MH  - Gene Expression Profiling
MH  - Hyperhomocysteinemia/*metabolism
MH  - Lens Subluxation/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress/physiology
MH  - RNA/*metabolism
MH  - RNA, Circular
OTO - NOTNLM
OT  - Circular RNA
OT  - Epigenetics
OT  - Eye diseases
OT  - Homocysteine
OT  - Inflammation
OT  - Oxidative-stress
EDAT- 2018/05/29 06:00
MHDA- 2019/02/12 06:00
CRDT- 2018/05/28 06:00
PHST- 2018/03/28 00:00 [received]
PHST- 2018/05/09 00:00 [revised]
PHST- 2018/05/23 00:00 [accepted]
PHST- 2018/05/29 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2018/05/28 06:00 [entrez]
AID - S0014-4835(18)30244-6 [pii]
AID - 10.1016/j.exer.2018.05.026 [doi]
PST - ppublish
SO  - Exp Eye Res. 2018 Sep;174:80-92. doi: 10.1016/j.exer.2018.05.026. Epub 2018 May 
      25.