Substance P in the corneal stroma regulates the severity of herpetic stromal keratitis lesions

Brandon S. Twardy, Rudragouda Channappanavar, Susmit Suvas

Research output: Contribution to journalArticle

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Abstract

Purpose. To determine whether substance P (SP) in herpes simplex virus-1 (HSV-1) infected cornea regulates the severity of herpetic stromal keratitis (HSK) lesions in a mouse model. Methods. C57BL/6 mice were infected ocularly with HSV-1 (RE). The corneas with HSK lesions, on Day 15 postinfection, were grouped on the basis of the corneal opacity as mild (≤2) or severe (>2). The amount of SP was determined in the corneas with mild or severe HSK lesions by enzyme immunosorbent assay (EIA) and confocal microscopy. Subconjunctival inoculation of spantide I, SP receptor antagonist, was carried out during the clinical phase of HSK. ELISA and flow cytometry were used to determine the level of cytokines, chemokines, and influx of immune cell types in the corneal lesions. Results. The authors determined a significantly higher level of SP in the corneas with severe HSK lesions in comparison with mild lesions. The corneas with a higher level of SP also exhibited higher amounts of proinflammatory cytokines (IL-6, IFN-γ) and chemokines (CCL3, CXCL2) when compared with the corneas with a lower level of SP. SP receptor NK1R expression was determined in CD45- and CD45+ cells in infected cornea. SP present in the corneal stroma of the eyes with severe HSK lesions colocalized with β-III tubulin + and IA b+ cell types. Subconjunctival inoculation of spantide I during the clinical phase of HSK resulted in significant reduction in the corneal opacity and angiogenesis. Conclusions. Collectively, these results demonstrate the relative contribution of substance P in regulating the clinical severity of HSK lesions in a mouse model.

Original languageEnglish (US)
Pages (from-to)8604-8613
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number12
DOIs
StatePublished - Nov 1 2011

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Herpetic Keratitis
Corneal Stroma
Substance P
Cornea
Corneal Opacity
Human Herpesvirus 1
Neurokinin-1 Receptor Antagonists
Corneal Neovascularization
Chemokine CXCL2
Cytokines
Chemokine CCL3
Neurokinin-1 Receptors
Immunosorbents
Enzyme Assays
Tubulin
Inbred C57BL Mouse
Chemokines
Confocal Microscopy
Interleukin-6
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Ophthalmology
  • Cellular and Molecular Neuroscience
  • Sensory Systems

Cite this

Substance P in the corneal stroma regulates the severity of herpetic stromal keratitis lesions. / Twardy, Brandon S.; Channappanavar, Rudragouda; Suvas, Susmit.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 12, 01.11.2011, p. 8604-8613.

Research output: Contribution to journalArticle

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abstract = "Purpose. To determine whether substance P (SP) in herpes simplex virus-1 (HSV-1) infected cornea regulates the severity of herpetic stromal keratitis (HSK) lesions in a mouse model. Methods. C57BL/6 mice were infected ocularly with HSV-1 (RE). The corneas with HSK lesions, on Day 15 postinfection, were grouped on the basis of the corneal opacity as mild (≤2) or severe (>2). The amount of SP was determined in the corneas with mild or severe HSK lesions by enzyme immunosorbent assay (EIA) and confocal microscopy. Subconjunctival inoculation of spantide I, SP receptor antagonist, was carried out during the clinical phase of HSK. ELISA and flow cytometry were used to determine the level of cytokines, chemokines, and influx of immune cell types in the corneal lesions. Results. The authors determined a significantly higher level of SP in the corneas with severe HSK lesions in comparison with mild lesions. The corneas with a higher level of SP also exhibited higher amounts of proinflammatory cytokines (IL-6, IFN-γ) and chemokines (CCL3, CXCL2) when compared with the corneas with a lower level of SP. SP receptor NK1R expression was determined in CD45- and CD45+ cells in infected cornea. SP present in the corneal stroma of the eyes with severe HSK lesions colocalized with β-III tubulin + and IA b+ cell types. Subconjunctival inoculation of spantide I during the clinical phase of HSK resulted in significant reduction in the corneal opacity and angiogenesis. Conclusions. Collectively, these results demonstrate the relative contribution of substance P in regulating the clinical severity of HSK lesions in a mouse model.",
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