Hydrogen sulfide is synthesized endogenously in both retinal artery and retina mostly via CSE
Introduction
H2S is an important gaseous mediator which has several effects such as the regulation of vascular tone in various arteries as well as the anti-apoptotic, anti-inflammatory and anti-oxidant properties (Badiei et al., 2019; Gheibi et al., 2018). It is known that H2S is also present in the eye and has physiological importance. There are 4 main enzymes that provide endogenous synthesis of H2S in the retina layer of the eye: cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST), cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) (Abe and Kimura, 1996; Du et al., 2017; Hughes et al., 2009). CBS and CSE were shown to be expressed in salamander, mouse and rat retina, while 3-MST in mouse and rat retina (Gersztenkorn et al., 2016; Huang et al., 2017; Mikami et al., 2011; Pong et al., 2007; Zeng et al., 2018).
Regarding to H2S, few studies are noticed in bovine eye. High levels of H2S were determined in the cornea and retina by spectrophotometric method. In the presence of the inhibitors of CBS and CSE enzymes namely, aminooxyacetic acid (AOAA) and dl-propargylglycine (PAG), a partial reduction in H2S levels was measured in the retina by 42%–56%, respectively, which revealed the role of CBS and CSE enzymes in the synthesis of H2S in bovine retina (Kulkarni et al., 2011). In addition, in our previous study, it was shown that the H2S donor, NaHS relaxed bovine retinal artery partially by the activation of Kv and Kir channels. Moreover, administration of L-cysteine, the precursor of H2S, induced a moderate relaxation which was significantly reduced in the presence of the (CBS) inhibitor, AOAA (Takir et al., 2015). The functional role of H2S in the regulation of retinal artery tone suggests that H2S can be synthesized endogenously in the retina and retinal artery (Du et al., 2017). However, no studies are evident showing the presence of 3-MST, CBS and CSE enzymes in bovine retina in terms of the molecular or immunohistochemical methods, despite the presentation of CBS and CSE enzymes in mice retina (Gersztenkorn et al., 2016; Mikami et al., 2011). In addition, none of these enzymes have been evaluated in the retinal artery.
Based on the data from previous studies, herein we aimed to evaluate whether the enzymes 3-MST, CBS and CSE that synthesize H2S are expressed in bovine retina and retinal artery. For this purpose, concentration levels and distribution profiles of enzymes were assessed by ELISA and immunofloresence microscobic analysis.
Section snippets
Preparation of bovine retina and retinal arteries
Bovine eyes (Brown Swiss [Montafoner], either sex, 2–4 years of age) were obtained from a local slaughterhouse and transported to the laboratory. Following transfer, extraocular muscles and connective tissues were dissected from the globe, the vitreous was removed and a stereomicroscope was used for dissection procedure (Zeiss, 2000; Oberkochen, Germany). The central retinal artery located underneath the optic disc was isolated completely and detached from the adhering retinal tissue.
The concentration levels of 3-MST, CBS and CSE
The role of 3-MST, CBS and CSE enzymes known to mediate H2S synthesis were evaluated in bovine retina and retinal artery by ELISA method.
Discussion
This study aimed to investigate the presence, amount and distribution of H2S synthesizing enzymes (3-MST, CBS and CSE) in the retinal artery and retina. To the best of our knowledge, this is the first study to evaluate the role of 3-MST, CBS and CSE enzymes in bovine retinal artery. There is also no study on protein levels of these enzymes in bovine retina. In this respect, our study provides original findings regarding the presence of H2S in the retina and retinal circulation, which may make a
Conclusion
The widespread expression of H2S synthesizing enzymes in the retina and the high enzyme levels determined in retinal artery, particularly in the endothelial layer, may suggest a protective role of H2S against retinal vascular diseases as well as a regulatory role in retinal vascular tone. The limitation of the study is that we could not determine the role of enzymes in the retina and retinal artery. Therefore, more studies are needed in this area to determine the activities and functions of
Declaration of competing interest
The authors declare that there is no conflict of interest.
Acknowledgements
This study was funded by TUBITAK (Scientific and Technological Research Council of Turkey) Project Number: 115S196; by Scientific Research Projects Coordination Unit of Istanbul University, Project Number: TDK-2018-29789; and by Scientific Research Projects Coordination Unit of Giresun University, Project Number: SAĞ-BAP-A-230218-81.
References (17)
- et al.
The possible role of hydrogen sulfide as an endogenous neuromodulator
J. Neurosci.
(1996) - et al.
Comparative localization of cystathionine beta synthases and cystathionine gamma lyase in canine, non-human primate and human retina
Exp. Eye Res.
(2019) - et al.
Role of hydrogen sulfide in retinal diseases
Front. Pharmacol.
(2017) - et al.
Hydrogen sulfide contributes to retinal neovascularization in Ischemia-Induced retinopathy
Investig. Ophthalmol. Vis. Sci.
(2016) - et al.
Regulation of vascular tone homeostasis by NO and H2S: implications in hypertension
Biochem. Pharmacol.
(2018) - et al.
Hydrogen sulfide: a gaseous signaling molecule modulates tissue homeostasis: implications in ophthalmic diseases
Cell Death Dis.
(2019) - et al.
Relevant variations and neuroprotecive effect of hydrogen sulfide in a rat glaucoma model
Neuroscience
(2017) - et al.
Making and working with hydrogen sulfide. The chemistry and generation of hydrogen sulfide in vitro and its measurement in vivo: a review
Free Radic. Biol. Med.
(2009)
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