PMID- 29560091
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 16
DP  - 2018 Feb 27
TI  - Epigenetic modifications in hyperhomocysteinemia: potential role in diabetic 
      retinopathy and age-related macular degeneration.
PG  - 12562-12590
LID - 10.18632/oncotarget.24333 [doi]
AB  - To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as 
      potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated 
      from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack 
      of the enzyme cystathionine beta-synthase (cbs(-/-) , cbs(+/-) and cbs(+/+) ), human 
      retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells 
      (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases 
      (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis. Differentially 
      expressed miRNAs in mice with HHcy were further compared with miRNA analysis of 
      diabetic mice retinas (STZ) and miRNAs within the exosomes released from 
      Hcy-treated RPEs. Differentially expressed miRNAs were further evaluated for 
      predicted target genes and associated pathways using Ingenuity Pathway Analysis. 
      HHcy significantly increased HDAC and DNMT activity in HRECs, ARPE-19, and cbs 
      mice retinas, whereas inhibition of HDAC and DNMT decreased Hcy-induced BRB 
      dysfunction. MiRNA profiling detected 127 miRNAs in cbs(+/-) and 39 miRNAs in 
      cbs(-/-) mice retinas, which were significantly differentially expressed compared 
      to cbs(+/+) . MiRNA pathway analysis showed their involvement in HDAC and DNMT 
      activation, endoplasmic reticulum (ER), and oxidative stresses, inflammation, 
      hypoxia, and angiogenesis pathways. Hcy-induced epigenetic modifications may be 
      involved in retinopathies associated with HHcy, such as age-related macular 
      degeneration and diabetic retinopathy.
FAU - Elmasry, Khaled
AU  - Elmasry K
AD  - Department of Oral Biology and Anatomy, Dental College of Georgia, Augusta 
      University, Augusta, GA, USA.
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), 
      Augusta University, Augusta, GA, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      August, GA, USA.
AD  - Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura 
      University, Mansoura, Egypt.
FAU - Mohamed, Riyaz
AU  - Mohamed R
AD  - Department of Oral Biology and Anatomy, Dental College of Georgia, Augusta 
      University, Augusta, GA, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      August, GA, USA.
FAU - Sharma, Isha
AU  - Sharma I
AD  - Department of Oral Biology and Anatomy, Dental College of Georgia, Augusta 
      University, Augusta, GA, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      August, GA, USA.
FAU - Elsherbiny, Nehal M
AU  - Elsherbiny NM
AD  - Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 
      Egypt.
FAU - Liu, Yutao
AU  - Liu Y
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), 
      Augusta University, Augusta, GA, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      August, GA, USA.
FAU - Al-Shabrawey, Mohamed
AU  - Al-Shabrawey M
AD  - Department of Oral Biology and Anatomy, Dental College of Georgia, Augusta 
      University, Augusta, GA, USA.
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), 
      Augusta University, Augusta, GA, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      August, GA, USA.
AD  - Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura 
      University, Mansoura, Egypt.
FAU - Tawfik, Amany
AU  - Tawfik A
AD  - Department of Oral Biology and Anatomy, Dental College of Georgia, Augusta 
      University, Augusta, GA, USA.
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), 
      Augusta University, Augusta, GA, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      August, GA, USA.
LA  - eng
GR  - R01 EY023315/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20180129
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5849155
OTO - NOTNLM
OT  - Gerotarget
OT  - age-related macular degeneration
OT  - blood retinal barrier
OT  - diabetic retinopathy
OT  - epigenetic modifications
OT  - hyperhomocysteinemia
COIS- CONFLICTS OF INTEREST None.
EDAT- 2018/03/22 06:00
MHDA- 2018/03/22 06:01
PMCR- 2018/02/27
CRDT- 2018/03/22 06:00
PHST- 2017/08/06 00:00 [received]
PHST- 2018/01/24 00:00 [accepted]
PHST- 2018/03/22 06:00 [entrez]
PHST- 2018/03/22 06:00 [pubmed]
PHST- 2018/03/22 06:01 [medline]
PHST- 2018/02/27 00:00 [pmc-release]
AID - 24333 [pii]
AID - 10.18632/oncotarget.24333 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jan 29;9(16):12562-12590. doi: 10.18632/oncotarget.24333. 
      eCollection 2018 Feb 27.