Skip to main content

Advertisement

SpringerLink
Log in

Oral administration of S-nitroso-l-glutathione (GSNO) provides anti-inflammatory and cytoprotective effects during ocular bacterial infections

  • Original Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Bacterial endophthalmitis is a severe complication of eye surgeries that can lead to vision loss. Current treatment involves intravitreal antibiotic injections that control bacterial growth but not inflammation. To identify newer therapeutic targets to promote inflammation resolution in endophthalmitis, we recently employed an untargeted metabolomics approach. This led to the discovery that the levels of S-nitroso-l-glutathione (GSNO) were significantly reduced in an experimental murine Staphylococcus aureus (SA) endophthalmitis model. In this study, we tested the hypothesis whether GSNO supplementation via different routes (oral, intravitreal) provides protection during bacterial endophthalmitis. Our results show that prophylactic administration of GSNO via intravitreal injections ameliorated SA endophthalmitis. Therapeutically, oral administration of GSNO was found to be most effective in reducing intraocular inflammation and bacterial burden. Moreover, oral GSNO treatment synergized with intravitreal antibiotic injections in reducing the severity of endophthalmitis. Furthermore, in vitro experiments using cultured human retinal Muller glia and retinal pigment epithelial (RPE) cells showed that GSNO treatment reduced SA-induced inflammatory mediators and cell death. Notably, both in-vivo and ex-vivo data showed that GSNO strengthened the outer blood-retinal barrier during endophthalmitis. Collectively, our study demonstrates GSNO as a potential therapeutic agent for the treatment of intraocular infections due to its dual anti-inflammatory and cytoprotective properties.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The data generated during the current study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

References

  1. Callegan MC et al (2002) Bacterial endophthalmitis: epidemiology, therapeutics, and bacterium–host interactions. Clin Microbiol Rev 15(1):111–124

    Article  PubMed  PubMed Central  Google Scholar 

  2. Flaxman SR et al (2017) Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob Health 5(12):e1221–e1234

    Article  PubMed  Google Scholar 

  3. Das S et al (2022) Innate immunity dysregulation in aging eye and therapeutic interventions. Ageing Res Rev 82:101768

    Article  CAS  PubMed  Google Scholar 

  4. Schwartz SG, Flynn HW Jr (2014) Update on the prevention and treatment of endophthalmitis. Expert Rev Ophthalmol 9(5):425–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dave VP et al (2014) Endophthalmitis following pars plana vitrectomy: a literature review of incidence, causative organisms, and treatment outcomes. Clin Ophthalmol 8:2183–2188

    PubMed  PubMed Central  Google Scholar 

  6. Grzybowski A et al (2020) The role of systemic antimicrobials in the treatment of endophthalmitis: a review and an international perspective. Ophthalmol Ther 9(3):485–498

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bui DK, Carvounis PE (2014) Evidence for and against intravitreous corticosteroids in addition to intravitreous antibiotics for acute endophthalmitis. Int Ophthalmol Clin 54(2):215–224

    Article  PubMed  PubMed Central  Google Scholar 

  8. van Langevelde P et al (1998) Antibiotic-induced lipopolysaccharide (LPS) release from Salmonella typhi: delay between killing by ceftazidime and imipenem and release of LPS. Antimicrob Agents Chemother 42(4):739–743

    Article  PubMed  PubMed Central  Google Scholar 

  9. van Langevelde P et al (1998) Antibiotic-induced release of lipoteichoic acid and peptidoglycan from Staphylococcus aureus: quantitative measurements and biological reactivities. Antimicrob Agents Chemother 42(12):3073–3078

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kumar A, Kumar A (2015) Role of Staphylococcus aureus virulence factors in inducing inflammation and vascular permeability in a mouse model of bacterial endophthalmitis. PLoS ONE 10(6):e0128423

    Article  PubMed  PubMed Central  Google Scholar 

  11. Heumann D et al (1994) Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes. Infect Immun 62(7):2715–2721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Callegan MC et al (1999) Pathogenesis of gram-positive bacterial endophthalmitis. Infect Immun 67(7):3348–3356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Astley RA et al (2016) Modeling intraocular bacterial infections. Prog Retin Eye Res 54:30–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Patel SN et al (2020) Prophylaxis measures for postinjection endophthalmitis. Surv Ophthalmol 65(4):408–420

    Article  PubMed  Google Scholar 

  15. Miller FC et al (2019) Targets of immunomodulation in bacterial endophthalmitis. Prog Retin Eye Res 73:100763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rajamani D et al (2016) Temporal retinal transcriptome and systems biology analysis identifies key pathways and hub genes in Staphylococcus aureus endophthalmitis. Sci Rep 6:21502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Graham SF et al (2016) Metabolic signatures of Huntington’s disease (HD): (1)H NMR analysis of the polar metabolome in post-mortem human brain. Biochim Biophys Acta 1862(9):1675–1684

    Article  CAS  PubMed  Google Scholar 

  18. Kumar A, Giri S, Kumar A (2016) 5-aminoimidazole-4-carboxamide ribonucleoside-mediated adenosine monophosphate-activated protein kinase activation induces protective innate responses in bacterial endophthalmitis. Cell Microbiol 18(12):1815–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Garcia G Jr et al (2020) Hippo signaling pathway has a critical role in Zika virus replication and in the pathogenesis of neuroinflammation. Am J Pathol 190(4):844–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Francis R et al (2020) Glycolytic inhibitor 2-deoxyglucose suppresses inflammatory response in innate immune cells and experimental staphylococcal endophthalmitis. Exp Eye Res 197:108079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Singh S et al (2021) Integrative metabolomics and transcriptomics identifies itaconate as an adjunct therapy to treat ocular bacterial infection. Cell Rep Med 2(5):100277

    Article  PubMed  PubMed Central  Google Scholar 

  22. Jarrell ZR et al (2022) Low-dose cadmium potentiates metabolic reprogramming following early-life respiratory syncytial virus infection. Toxicol Sci 188(1):62–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Patil CD et al (2022) Postinfection metabolic reprogramming of the murine trigeminal ganglion limits herpes simplex virus-1 replication. MBio 13(5):e0219422

    Article  PubMed  Google Scholar 

  24. Globisch D et al (2013) Onchocerca volvulus-neurotransmitter tyramine is a biomarker for river blindness. Proc Natl Acad Sci USA 110(11):4218–4223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Broniowska KA, Diers AR, Hogg N (2013) S-nitrosoglutathione. Biochim Biophys Acta 1830(5):3173–3181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Begara-Morales JC et al (2018) Nitric oxide buffering and conditional nitric oxide release in stress response. J Exp Bot 69(14):3425–3438

    Article  CAS  PubMed  Google Scholar 

  27. Bogdan C (2015) Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol 36(3):161–178

    Article  CAS  PubMed  Google Scholar 

  28. Andrew PJ, Mayer B (1999) Enzymatic function of nitric oxide synthases. Cardiovasc Res 43(3):521–531

    Article  CAS  PubMed  Google Scholar 

  29. Rosales MA et al (2014) S-nitrosoglutathione inhibits inducible nitric oxide synthase upregulation by redox posttranslational modification in experimental diabetic retinopathy. Invest Ophthalmol Vis Sci 55(5):2921–2932

    Article  CAS  PubMed  Google Scholar 

  30. Choi M et al (2020) Chitosan-based nitric oxide-releasing dressing for anti-biofilm and in vivo healing activities in MRSA biofilm-infected wounds. Int J Biol Macromol 142:680–692

    Article  CAS  PubMed  Google Scholar 

  31. Liu Z et al (1998) S-transnitrosation reactions are involved in the metabolic fate and biological actions of nitric oxide. J Pharmacol Exp Ther 284(2):526–534

    CAS  PubMed  Google Scholar 

  32. Hogg N (2000) Biological chemistry and clinical potential of S-nitrosothiols. Free Radic Biol Med 28(10):1478–1486

    Article  CAS  PubMed  Google Scholar 

  33. Hlaing SP et al (2018) S-nitrosoglutathione loaded poly(lactic-co-glycolic acid) microparticles for prolonged nitric oxide release and enhanced healing of methicillin-resistant Staphylococcus aureus-infected wounds. Eur J Pharm Biopharm 132:94–102

    Article  CAS  PubMed  Google Scholar 

  34. de Oliveira CP et al (2008) Prevention and reversion of nonalcoholic steatohepatitis in OB/OB mice by S-nitroso-N-acetylcysteine treatment. J Am Coll Nutr 27(2):299–305

    Article  PubMed  Google Scholar 

  35. Barnett SD, Buxton ILO (2017) The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy. Crit Rev Biochem Mol Biol 52(3):340–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. de Souza GF et al (2006) Leishmanicidal activity of primary S-nitrosothiols against Leishmania major and Leishmania amazonensis: implications for the treatment of cutaneous leishmaniasis. Nitric Oxide 15(3):209–216

    Article  PubMed  Google Scholar 

  37. Liu C et al (2017) Nitric oxide-generating compound GSNO suppresses porcine circovirus type 2 infection in vitro and in vivo. BMC Vet Res 13(1):59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Prasad R et al (2007) GSNO attenuates EAE disease by S-nitrosylation-mediated modulation of endothelial–monocyte interactions. Glia 55(1):65–77

    Article  PubMed  Google Scholar 

  39. Khan M et al (2005) S-nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke. J Cereb Blood Flow Metab 25(2):177–192

    Article  CAS  PubMed  Google Scholar 

  40. Haq E et al (2007) S-nitrosoglutathione prevents interphotoreceptor retinoid-binding protein (IRBP(161–180))-induced experimental autoimmune uveitis. J Ocul Pharmacol Ther 23(3):221–231

    Article  CAS  PubMed  Google Scholar 

  41. Guest JM et al (2018) Isavuconazole for treatment of experimental fungal endophthalmitis caused by Aspergillus fumigatus. Antimicrob Agents Chemother 62(11):e01537–18

  42. Peter B et al (2013) ESCRS guidelines for prevention and treatment of endophthalmitis following cataract surgery: data, dilemmas and conclusions. Co Dublin, Ireland: The European Society for Cataract & Refractive Surgeons

  43. Sadiq MA et al (2015) Endogenous endophthalmitis: diagnosis, management, and prognosis. J Ophthalmic Inflamm Infect 5(1):32

    Article  PubMed  PubMed Central  Google Scholar 

  44. Chakravortty D, Hensel M (2003) Inducible nitric oxide synthase and control of intracellular bacterial pathogens. Microbes Infect 5(7):621–627

    Article  CAS  PubMed  Google Scholar 

  45. Kumar A et al (2013) Muller glia in retinal innate immunity: a perspective on their roles in endophthalmitis. Crit Rev Immunol 33(2):119–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kumar A, Shamsuddin N (2012) Retinal Muller glia initiate innate response to infectious stimuli via toll-like receptor signaling. PLoS ONE 7(1):e29830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shamsuddin N, Blair J, Kumar A (2011) Toll like receptor 2 mediates the innate immune response of retinal Muller glia to Staphylococcus aureus. Invest Ophthalmol Vis Sci 52(14):2959–2959

    Google Scholar 

  48. Das S et al (2022) Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection. iScience 25(9):104862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Singh PK, Kumar A (2016) Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis. Cell Death Discov 2(1):16034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Coburn PS et al (2015) Blood-retinal barrier compromise and endogenous Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 56(12):7303–7311

    Article  PubMed  PubMed Central  Google Scholar 

  51. Singh S, Singh S, Kumar A (2022) Systemic Candida albicans infection in mice causes endogenous endophthalmitis via breaching the outer blood-retinal barrier. Microbiol Spectr 10(4):e0165822

    Article  PubMed  Google Scholar 

  52. Coburn PS et al (2016) Bloodstream-to-eye infections are facilitated by outer blood-retinal barrier dysfunction. PLoS ONE 11(5):e0154560

    Article  PubMed  PubMed Central  Google Scholar 

  53. Durand ML (2017) Bacterial and fungal endophthalmitis. Clin Microbiol Rev 30(3):597–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Brockhaus L et al (2019) Revisiting systemic treatment of bacterial endophthalmitis: a review of intravitreal penetration of systemic antibiotics. Clin Microbiol Infect 25(11):1364–1369

    Article  CAS  PubMed  Google Scholar 

  55. Hariprasad SM et al (2006) Vitreous and aqueous penetration of orally administered moxifloxacin in humans. Arch Ophthalmol 124(2):178–182

    Article  CAS  PubMed  Google Scholar 

  56. Etminan M et al (2012) Oral fluoroquinolones and the risk of retinal detachment. JAMA 307(13):1414–1419

    Article  CAS  PubMed  Google Scholar 

  57. Wu XN et al (2022) Emerging antibiotic resistance patterns affect visual outcome treating acute endophthalmitis. Antibiotics (Basel) 11(7):843

  58. Zegans ME et al (2002) The role of bacterial biofilms in ocular infections. DNA Cell Biol 21(5–6):415–420

    Article  CAS  PubMed  Google Scholar 

  59. Qian H et al (2022) Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials. Mater Today Bio 16:100419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Smith A et al (2001) Fluoroquinolones: place in ocular therapy. Drugs 61(6):747–761

    Article  CAS  PubMed  Google Scholar 

  61. Ahmed S et al (2014) Intraocular penetration of systemic antibiotics in eyes with penetrating ocular injury. J Ocul Pharmacol Ther 30(10):823–830

    Article  PubMed  Google Scholar 

  62. Garcia-Saenz MC et al (2001) Human aqueous humor levels of oral ciprofloxacin, levofloxacin, and moxifloxacin. J Cataract Refract Surg 27(12):1969–1974

    Article  CAS  PubMed  Google Scholar 

  63. Alfaro DV, Liggett PE (1994) Intravenous cefazolin in penetrating eye injuries. I. Effects of trauma and multiple doses on intraocular delivery. Graefes Arch Clin Exp Ophthalmol 232(4):238–241

    Article  CAS  PubMed  Google Scholar 

  64. Birnbaum FA, Gupta G (2016) The role of early vitrectomy in the treatment of fungal endogenous endophthalmitis. Retin Cases Brief Rep 10(3):232–235

    Article  PubMed  Google Scholar 

  65. Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109(Suppl):S81-96

    Article  CAS  PubMed  Google Scholar 

  66. Okazaki T et al (2003) Phosphorylation of serine 276 is essential for p65 NF-kappaB subunit-dependent cellular responses. Biochem Biophys Res Commun 300(4):807–812

    Article  CAS  PubMed  Google Scholar 

  67. Kumar A et al (2022) Essential role of NLRP3 inflammasome in mediating IL-1β production and the pathobiology of Staphylococcus aureus endophthalmitis. Infect Immun 90(5):e0010322

    Article  PubMed  Google Scholar 

  68. Kelley N et al (2019) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci 20(13):3328

  69. Griffith OW, Stuehr DJ (1995) Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol 57:707–736

    Article  CAS  PubMed  Google Scholar 

  70. Moncada S, Bolanos JP (2006) Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97(6):1676–1689

    Article  CAS  PubMed  Google Scholar 

  71. Goureau O, Regnier-Ricard F, Courtois Y (1999) Requirement for nitric oxide in retinal neuronal cell death induced by activated Muller glial cells. J Neurochem 72(6):2506–2515

    Article  CAS  PubMed  Google Scholar 

  72. Schneemann A et al (2003) Elevation of nitric oxide production in human trabecular meshwork by increased pressure. Graefes Arch Clin Exp Ophthalmol 241(4):321–326

    Article  CAS  PubMed  Google Scholar 

  73. Jeong H et al (2020) Sustained nitric oxide-providing small molecule and precise release behavior study for glaucoma treatment. Mol Pharm 17(2):656–665

    CAS  PubMed  Google Scholar 

  74. Kim JJ, Kim YH, Lee MY (2009) Proteomic characterization of differentially expressed proteins associated with no stress in retinal ganglion cells. BMB Rep 42(7):456–461

    Article  CAS  PubMed  Google Scholar 

  75. Moyer AL et al (2009) Bacillus cereus-induced permeability of the blood-ocular barrier during experimental endophthalmitis. Invest Ophthalmol Vis Sci 50(8):3783–3793

    Article  PubMed  Google Scholar 

  76. Obert E et al (2017) Targeting the tight junction protein, zonula occludens-1, with the connexin43 mimetic peptide, alphaCT1, reduces VEGF-dependent RPE pathophysiology. J Mol Med (Berl) 95(5):535–552

    Article  CAS  PubMed  Google Scholar 

  77. Khan M et al (2012) The inhibitory effect of S-nitrosoglutathione on blood-brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke. J Neurochem 123(Suppl 2):86–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Khan M et al (2011) S-nitrosoglutathione reduces oxidative injury and promotes mechanisms of neurorepair following traumatic brain injury in rats. J Neuroinflamm 8:78

    Article  CAS  Google Scholar 

  79. Ray KJ et al (2014) Early addition of topical corticosteroids in the treatment of bacterial keratitis. JAMA Ophthalmol 132(6):737–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cohen EJ (2009) The case against the use of steroids in the treatment of bacterial keratitis. Arch Ophthalmol 127(1):103–104

    Article  PubMed  Google Scholar 

  81. Ming H et al (2023) A mini review of S-Nitrosoglutathione loaded nano/micro-formulation strategies. Nanomaterials (Basel) 13(2):224

  82. Novick R (1967) Properties of a cryptic high-frequency transducing phage in Staphylococcus aureus. Virology 33(1):155–166

    Article  CAS  PubMed  Google Scholar 

  83. Singh PK et al (2020) Aging, but not sex and genetic diversity, impacts the pathobiology of bacterial endophthalmitis. Invest Ophthalmol Vis Sci 61(14):5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Paigen B et al (1985) Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis 57(1):65–73

    Article  CAS  PubMed  Google Scholar 

  85. Kumar A et al (2010) Toll-like receptor 2 ligand-induced protection against bacterial endophthalmitis. J Infect Dis 201(2):255–263

    Article  CAS  PubMed  Google Scholar 

  86. Talreja D et al (2014) Pathogenicity of ocular isolates of Acinetobacter baumannii in a mouse model of bacterial endophthalmitis. Invest Ophthalmol Vis Sci 55(4):2392–2402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Singh S et al (2021) Povidone-Iodine attenuates viral replication in ocular cells: implications for ocular transmission of RNA viruses. Biomolecules 11(5):753

  88. Das S, Singh S, Kumar A (2021) Bacterial burden declines but neutrophil infiltration and ocular tissue damage persist in experimental Staphylococcus epidermidis endophthalmitis. Front Cell Infect Microbiol 11:780648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Singh S, Singh PK, Kumar A (2023) Butyrate ameliorates intraocular bacterial infection by promoting autophagy and attenuating the inflammatory response. Infect Immun 91(1):e00252-e322

    Article  PubMed  Google Scholar 

  90. Singh S et al (2018) Dengue virus or NS1 protein induces trans-endothelial cell permeability associated with VE-Cadherin and RhoA phosphorylation in HMEC-1 cells preventable by Angiopoietin-1. J Gen Virol 99(12):1658–1670

    Article  CAS  PubMed  Google Scholar 

  91. Kerur N et al (2013) TLR-independent and P2X7-dependent signaling mediate Alu RNA-induced NLRP3 inflammasome activation in geographic atrophy. Invest Ophthalmol Vis Sci 54(12):7395–7401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Das S et al (2018) Identification of a novel gene in ROD9 island of Salmonella enteritidis involved in the alteration of virulence-associated genes expression. Virulence 9(1):348–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sun J et al (2003) Measurement of nitric oxide production in biological systems by using Griess reaction assay. Sensors 3(8):276–284

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by National Institute of Health (NIH) Grants R01 EY027381, R01EY026964, and R21AI135583 awarded to AK. We would like to acknowledge the Research to Prevent Blindness (RPB) for their unrestricted grant to the Kresge Eye Institute/Department of Ophthalmology, Visual, and Anatomical Sciences. The immunology core is supported by an NEI vision center grant P30EY004068. The funders had no role in the design of the study, data collection, data analysis, interpretation of the results, or in the decision to submit the work for publication.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, 4717 St. Antoine, Detroit, MI, 48201, USA

    Susmita Das, Zeeshan Ahmad, Sneha Singh, Sukhvinder Singh, Robert Emery Wright III & Ashok Kumar

  2. Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA

    Ashok Kumar

  3. Department of Neurology, Henry Ford Health System, Detroit, MI, USA

    Shailendra Giri

Authors
  1. Susmita Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zeeshan Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sneha Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sukhvinder Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Emery Wright III
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shailendra Giri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ashok Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AK conceived the idea, provided direction and funding for the project, and finalized the manuscript. SD designed and performed the experiments, analyzed the data, prepared manuscript, and figures, and revised the final manuscript. ZA, SS and SS helped with few experiments and edited the manuscript. RW performed sectioning and imaging and edited the manuscript. SG helped in conceptualization of the idea, provided critical feedback in experimental design, and edited the final manuscript.

Corresponding author

Correspondence to Ashok Kumar.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest. The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (MP4 79 KB)

Supplementary file2 (MP4 91 KB)

Supplementary file3 (MP4 138 KB)

Supplementary file4 (DOCX 133891 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Das, S., Ahmad, Z., Singh, S. et al. Oral administration of S-nitroso-l-glutathione (GSNO) provides anti-inflammatory and cytoprotective effects during ocular bacterial infections. Cell. Mol. Life Sci. 80, 309 (2023). https://doi.org/10.1007/s00018-023-04963-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00018-023-04963-w

Keywords

Search

Navigation