Abstract
Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) degeneration. Hydrogen sulfide (H2S) is a potent neurotransmitter and has been proven to protect RGCs against glaucomatous injury in vitro and in vivo. This study is to provide an overall insight of H2S’s role in glaucoma pathophysiology. Ischemia-reperfusion injury (I/R) was induced in Sprague-Dawley rats (n = 12) by elevating intraocular pressure to 55 mmHg for 60 min. Six of the animals received intravitreal injection of H2S precursor prior to the procedure and the retina was harvested 24 h later. Contralateral eyes were assigned as control. RGCs were quantified and compared within the groups. Retinal proteins were analyzed via label-free mass spectrometry based quantitative proteomics approach. The pathways of the differentially expressed proteins were identified by ingenuity pathway analysis (IPA). H2S significantly improved RGC survival against I/R in vivo (p < 0.001). In total 1115 proteins were identified, 18 key proteins were significantly differentially expressed due to I/R and restored by H2S. Another 11 proteins were differentially expressed following H2S. IPA revealed a significant H2S-mediated activation of pathways related to mitochondrial function, iron homeostasis and vasodilation. This study provides first evidence of the complex role that H2S plays in protecting RGC against I/R.
Highlights
Glaucoma is one of the leading causes of irreversible blindness worldwide [1] and is characterized by progressive optic nerve and retinal ganglion cell (RGC) degeneration [2]
Alteration of endogenous H2S levels in the retina is linked to different pathological conditions, and its exogenous donors have been shown to exhibit potential in protecting retinal ganglion cells against insults such as diabetic retinopathy, ischemia-reperfusion injury and N-methyl-D-aspartic acid (NMDA)-induced excitatory neurotoxicity [16,19,20]
We showed in our previous study that endogenous H2S synthesis via 3-mercaptopyruvate sulfurtransferase (3-MST) is increased in a glaucoma animal model after seven weeks of intraocular pressure (IOP) elevation
Summary
Glaucoma is one of the leading causes of irreversible blindness worldwide [1] and is characterized by progressive optic nerve and retinal ganglion cell (RGC) degeneration [2]. Drugs inhibiting NO formation showed protective effects in the retina against elevated IOP in glaucoma animal models [11,12,13]. The CO production system in the retina has been highlighted as a protective mechanism, its protecting role is demonstrated in the regulation of Ischemia-reperfusion (I/R) -induced damage, protecting retinal ganglion cells against oxidative damage, increases retinal and choroidal blood flows and downregulating inflammatory response in the anterior segment of the eye [14,15,16]. Alteration of endogenous H2S levels in the retina is linked to different pathological conditions, and its exogenous donors have been shown to exhibit potential in protecting retinal ganglion cells against insults such as diabetic retinopathy, ischemia-reperfusion injury and N-methyl-D-aspartic acid (NMDA)-induced excitatory neurotoxicity [16,19,20]. We used mass spectrometry-based proteomics to elucidate how protein expression changes at the cellular level, in H2S-treated and H2S-untreated retinae of Sprague-Dawley rats that underwent acute elevated IOP (ischemia-reperfusion injury), and to provide a more precise direction for further studies
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