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Mahavir Singh, Akash George, Rubens P Homme, Avisek Majumder, Suresh Tyagi; Evaluation of hydrogen sulfide (H2S) effects on visual functions and pyroptosis in a mouse model of hyperhomocysteinemia. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6067.
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© ARVO (1962-2015); The Authors (2016-present)
Elevated homocysteine (Hcy) levels known as hyperhomocysteinemia (HHcy) result into serious eye conditions. Cystathionine β-synthase (CBS) is a H2S producing enzyme and mice lacking CBS have extremely high concentrations of circulating Hcy in their systems. H2S is a highly potent anti-oxidant, anti-inflammatory and cytoprotective agent and thus plays crucial roles via inhibiting ischemic injury, reducing oxidative-stress damage, regulating cell death and reducing the inflammation. We hypothesized that inflammation driven form of cell death (i.e. pyroptosis), retinal degeneration and loss of visual functions might be treated successfully by H2S administration. To test this hypothesis, we employed CBS knock-out (KO) mice in our study.
Adult male CBS-KO and wild type (WT) mice were used with or without H2S administration for varying period of time. Experimental groups were as follows: WT; WT+H2S; CBS-KO and CBS-KO+H2S. Vision test in treated and untreated animal groups along with a battery of cellular, biochemical, histological and imaging tools were employed on retinal cells/lysates prepared from treated and untreated mice groups to investigate retinal architecture and metabolic profile of the retinae by measuring m-TOR, AMPK, caspase-1, ROS, MMPs levels, etc.
The retinal angiography and BSA-FITC permeability data revealed significant vascular dysfunction as a result of the damaged vessels in the CBS-KO groups and that H2S treatment could help alleviate some of these changes in the retina as revealed by the vision test. The findings suggest that H2S was able to modify some of the harmful effects in the H2S treated groups successfully. Furthermore, H2S administration was able to reduce HHcy induced oxidative-stress markers, pyroptosis, and MMPs levels in the eyes of treated animals.
Our results suggest that H2S can be used as a therapeutic agent to help treat ocular diseases especially the ones which affect retinae as a result of neuro-degeneration and related neuro-vascular dysfunction; the hallmarks of chronic retinal diseases. Since retina is a direct connection to the vitreous body it appears to be a perfect match to gaseous transmitter treatment modality.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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