PMID- 31131233
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2222-3959 (Print)
IS  - 2227-4898 (Electronic)
IS  - 2222-3959 (Linking)
VI  - 12
IP  - 5
DP  - 2019
TI  - Hydrogen sulfide intervention in cystathionine-beta-synthase mutant mouse helps 
      restore ocular homeostasis.
PG  - 754-764
LID - 10.18240/ijo.2019.05.09 [doi]
AB  - AIM: To investigate the applications of hydrogen sul fi de (H(2)S) in eye-specific 
      ailments in mice. METHODS: Heterozygous cystathionine-beta-synthase (CBS(+/-)) and 
      wild-type C57BL/6J (WT) mice fed with or without high methionine diet (HMD) were 
      administered either phosphate buffered saline (PBS) or the slow-release H(2)S 
      donor: GYY4137. Several analyses were performed to study GYY4137 effects by 
      examining retinal lysates for key protein expressions along with plasma glutamate 
      and glutathione estimations. Intraocular pressure (IOP) was monitored during 
      GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein 
      isothiocyanate (BSA-FITC) angiographies were performed for examining vasculature 
      and its permeability post-treatment. Vision-guided behavior was also tested 
      employing novel object recognition test (NORT) and light-dark box test (LDBT) 
      recordings. RESULTS: CBS deficiency (CBS(+/-)) coupled with HMD led disruption of 
      methionine/homocysteine (Hcy) metabolism leading to hyperhomocysteinemia (HHcy) 
      in CBS(+/-) mice as reflected by increased Hcy, and s-adenosylhomocysteine 
      hydrolase (SAHH) levels. Unlike CBS, cystathionine-gamma lyase (CSE), 
      methylenetetrahydrofolate reductase (MTHFR) levels which were reduced but 
      compensated by GYY4137 intervention. Heightened oxidative and endoplasmic 
      reticulum (ER) stress responses were mitigated by GYY4137 effects along with 
      enhanced glutathione (GSH) levels. Increased glutamate levels in CBS(+/-) strain 
      were prominent than WT mice and these mice also exhibited higher IOP that was 
      lowered by GYY4137 treatment. CBS deficiency also resulted in vision-guided 
      behavioral impairment as revealed by NORT and LDBT findings. Interestingly, 
      GYY4137 was able to improve CBS(+/-) mice behavior together with lowering their 
      glutamate levels. Blood-retinal barrier (BRB) appeared compromised in CBS(+/-) 
      with vessels' leakage that was mitigated in GYY4137 treated group. This 
      corroborated the results for occludin (an integral plasma membrane protein of the 
      cellular tight junctions) stabilization. CONCLUSION: Findings reveal that 
      HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and vascular 
      permeability alone or together can compromise ocular health and that GYY4137 
      could serve as a potential therapeutic agent for treating HHcy induced ocular 
      disorders.
FAU - George, Akash K
AU  - George AK
AD  - Eye and Vision Science Laboratory, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
FAU - Homme, Rubens P
AU  - Homme RP
AD  - Eye and Vision Science Laboratory, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
FAU - Majumder, Avisek
AU  - Majumder A
AD  - Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 
      University of California San Francisco, San Francisco, CA 94158, USA.
FAU - Laha, Anwesha
AU  - Laha A
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
FAU - Metreveli, Naira
AU  - Metreveli N
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
FAU - Sandhu, Harpal S
AU  - Sandhu HS
AD  - Department of Ophthalmology and Visual Sciences; Kentucky Lions Eye Center, 
      University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
FAU - Singh, Mahavir
AU  - Singh M
AD  - Eye and Vision Science Laboratory, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky 40202, USA.
LA  - eng
GR  - R01 NS084823/NS/NINDS NIH HHS/United States
GR  - U01 HL074815/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20190518
PL  - China
TA  - Int J Ophthalmol
JT  - International journal of ophthalmology
JID - 101553860
PMC - PMC6520274
OTO - NOTNLM
OT  - blood-retinal barrier integrity
OT  - endoplasmic reticulum stress
OT  - glutamate cytotoxicity
OT  - inflammation
OT  - mice
OT  - oxidative stress
EDAT- 2019/05/28 06:00
MHDA- 2019/05/28 06:01
PMCR- 2019/05/18
CRDT- 2019/05/28 06:00
PHST- 2018/07/20 00:00 [received]
PHST- 2019/02/24 00:00 [accepted]
PHST- 2019/05/28 06:00 [entrez]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2019/05/28 06:01 [medline]
PHST- 2019/05/18 00:00 [pmc-release]
AID - ijo-12-05-754 [pii]
AID - 10.18240/ijo.2019.05.09 [doi]
PST - epublish
SO  - Int J Ophthalmol. 2019 May 18;12(5):754-764. doi: 10.18240/ijo.2019.05.09. 
      eCollection 2019.