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Role of Hydrogen Sulfide (H 2 S) on Homocysteine Mediated Glutamate Excitotoxicity, Endoplasmic Reticulum Stress and Pyroptosis in Retina
Author(s) -
George Akash K.,
Singh Mahavir,
Homme Rubens P.,
Majumder Avisek,
Tyagi Suresh
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.748.5
Subject(s) - endoplasmic reticulum , retina , retinal , homocysteine , chemistry , hyperhomocysteinemia , endocrinology , cystathionine beta synthase , medicine , biochemistry , biology , methionine , neuroscience , amino acid
High levels of circulating homocysteine (Hcy) in the blood i.e. hyperhomocysteinemia (HHcy) have been linked to several visual disorders and are associated with impairment of retinal functions. The precise molecular mechanisms of how HHcy affects the retinal biology are unknown. The main objective of this study was to investigate the effect of HHcy on retinal glutamatergic dysfunction, endoplasmic reticulum (ER) stress and inflammation and whether H 2 S; a potent anti‐oxidant, anti‐inflammatory, vasoactive gas can mitigate the Hcy effects. We used HHcy mouse model CBS+/− and the wild type (WT) treated with H 2 S donor GYY4137 (133 μM/kg‐1/d‐1). The animal groups were designated as follows: Group‐I: WT control + No treatment; Group‐II: CBS+/− +No treatment, Group‐II: CBS+/− + GYY4137 and Group‐II: WT control + GYY4137. Novel Object Recognition Test (NORT) and Light Dark Box Test (LDBT) were employed to check the visual functions. The bovine serum albumin (BSA) labeled fluorescein isothiocyanate (FITC‐BSA) was used to study the vascular permeability in the retinas of these mice from all the four groups. Western blotting and qPCR were carried out to analyze the protein and mRNA expression levels in the retinas from all the groups. Our NORT and LDBT data showed a significant impairment of the visual functions in the CBS+/− mice as compared to the WT control mice. We also found a significant amount of leakage in the blood vessels in the retina of the CBS+/− mice in comparison to the WT control mice and that was mitigated by GYY4137 treatment. We noticed oxidative stress, ER‐stress, Glutamate excitotoxicity and inflammation were prominent in the tissue samples collected from the CBS mice in comparison to WT controls. Interestingly, we found that GYY4137 treatment could mitigate the glutamatergic dysfunction, ER stress, neurovascular dysfunction and the pyroptosis along with improvement in the visual functions in the CBS+/− mice treated with H 2 S. Support or Funding Information NIH Heart, Lung & Blood Institute (HL‐74815), Institute of Neurological Disorders & Stroke (NS‐084823). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .