PMID- 32751132
OWN - NLM
STAT- MEDLINE
DCOM- 20210309
LR  - 20210901
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 10
IP  - 8
DP  - 2020 Jul 29
TI  - Implication of Hyperhomocysteinemia in Blood Retinal Barrier (BRB) Dysfunction.
LID - 10.3390/biom10081119 [doi]
LID - 1119
AB  - Elevated plasma homocysteine (Hcy) level, known as hyperhomocysteinemia (HHcy) 
      has been linked to different systemic and neurological diseases, well-known as a 
      risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and has 
      been identified as a risk factor for several ocular disorders, such as diabetic 
      retinopathy (DR) and age-related macular degeneration (AMD). Different mechanisms 
      have been proposed to explain HHcy-induced visual dysfunction, including 
      oxidative stress, upregulation of inflammatory mediators, retinal ganglion cell 
      apoptosis, and extracellular matrix remodeling. Our previous studies using in 
      vivo and in vitro models of HHcy have demonstrated that Hcy impairs the function 
      of both inner and outer blood retinal barrier (BRB). Dysfunction of BRB is a 
      hallmark of vision loss in DR and AMD. Our findings highlighted oxidative stress, 
      ER stress, inflammation, and epigenetic modifications as possible mechanisms of 
      HHcy-induced BRB dysfunction. In addition, we recently reported HHcy-induced 
      brain inflammation as a mechanism of blood-brain barrier (BBB) dysfunction and 
      pathogenesis of Alzheimer's disease (AD). Moreover, we are currently 
      investigating the activation of glutamate receptor N-methyl-d-aspartate receptor 
      (NMDAR) as the molecular mechanism for HHcy-induced BRB dysfunction. This review 
      focuses on the studied effects of HHcy on BRB and the controversial role of HHcy 
      in the pathogenesis of aging neurological diseases such as DR, AMD, and AD. We 
      also highlight the possible mechanisms for such deleterious effects of HHcy.
FAU - Tawfik, Amany
AU  - Tawfik A
AUID- ORCID: 0000-0002-0245-8256
AD  - Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, 
      Augusta University, Augusta, GA 30912, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      Augusta, GA 30912, USA.
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), 
      Augusta University, Augusta, GA 30912, USA.
AD  - Department of Ophthalmology, MCG, Augusta University, Augusta, GA 30912, USA.
FAU - Samra, Yara A
AU  - Samra YA
AD  - Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, 
      Augusta University, Augusta, GA 30912, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      Augusta, GA 30912, USA.
AD  - Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt.
FAU - Elsherbiny, Nehal M
AU  - Elsherbiny NM
AD  - Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, 
      Augusta University, Augusta, GA 30912, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      Augusta, GA 30912, USA.
AD  - Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt.
FAU - Al-Shabrawey, Mohamed
AU  - Al-Shabrawey M
AD  - Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, 
      Augusta University, Augusta, GA 30912, USA.
AD  - James and Jean Culver Vision Discovery Institute, MCG, Augusta University, 
      Augusta, GA 30912, USA.
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia (MCG), 
      Augusta University, Augusta, GA 30912, USA.
AD  - Department of Ophthalmology, MCG, Augusta University, Augusta, GA 30912, USA.
AD  - Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, 
      Egypt.
LA  - eng
GR  - P30 EY031631/EY/NEI NIH HHS/United States
GR  - R01 EY029751/EY/NEI NIH HHS/United States
GR  - R01 EY030054/EY/NEI NIH HHS/United States
GR  - 16SDG3070001/American Heart Association/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200729
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Aging
MH  - Alzheimer Disease/etiology/metabolism/physiopathology
MH  - Animals
MH  - Blood-Retinal Barrier/metabolism/*physiopathology
MH  - Diabetic Retinopathy/etiology/metabolism/physiopathology
MH  - Endoplasmic Reticulum Stress
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/complications/metabolism/*physiopathology
MH  - Macular Degeneration/etiology/metabolism/physiopathology
MH  - Oxidative Stress
PMC - PMC7463551
OTO - NOTNLM
OT  - blood brain barrier
OT  - blood retinal barrier
OT  - dysfunction
OT  - hyperhomocysteinemia
OT  - mechanisms
COIS- The authors declare no conflict of interest.
EDAT- 2020/08/06 06:00
MHDA- 2021/03/10 06:00
PMCR- 2020/08/01
CRDT- 2020/08/06 06:00
PHST- 2020/06/20 00:00 [received]
PHST- 2020/07/24 00:00 [revised]
PHST- 2020/07/27 00:00 [accepted]
PHST- 2020/08/06 06:00 [entrez]
PHST- 2020/08/06 06:00 [pubmed]
PHST- 2021/03/10 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - biom10081119 [pii]
AID - biomolecules-10-01119 [pii]
AID - 10.3390/biom10081119 [doi]
PST - epublish
SO  - Biomolecules. 2020 Jul 29;10(8):1119. doi: 10.3390/biom10081119.