Related Experiment Video
Updated: May 28, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
Substance P in the corneal stroma regulates the severity of herpetic stromal keratitis lesions
Brandon S Twardy1, Rudragouda Channappanavar, Susmit Suvas
1Department of Biological Sciences, Oakland University, Rochester, Michigan, USA.
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.
Insights
Substance P (SP) levels correlate with herpetic stromal keratitis (HSK) severity in HSV-1 infected mice. Blocking the SP receptor reduced lesion opacity and blood vessel growth, indicating SP's role in HSK.
Area of Science:
- Ophthalmology
- Immunology
- Neuroscience
Background:
- Herpetic stromal keratitis (HSK) is a significant cause of vision loss.
- The role of neuropeptides like substance P (SP) in HSK pathogenesis is not fully understood.
- Understanding molecular mediators is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of substance P (SP) in regulating the severity of herpetic stromal keratitis (HSK) lesions.
- To determine the correlation between SP levels and HSK lesion severity in a mouse model.
- To assess the therapeutic potential of blocking the SP receptor in HSK.
Main Methods:
- Ocular infection of C57BL/6 mice with herpes simplex virus-1 (HSV-1).
- Quantification of SP levels in corneas with mild versus severe HSK lesions using ELISA and confocal microscopy.
- Administration of spantide I (SP receptor antagonist) and assessment of HSK severity, inflammation, and neovascularization.
Main Results:
- Significantly higher SP levels were found in corneas with severe HSK lesions compared to mild lesions.
- Elevated SP correlated with increased pro-inflammatory cytokines (IL-6, IFN-γ) and chemokines (CCL3, CXCL2).
- Blocking the SP receptor with spantide I significantly reduced corneal opacity and angiogenesis.
Conclusions:
- Substance P plays a key role in regulating the clinical severity of HSK.
- Targeting the SP pathway may offer a therapeutic strategy for managing HSK.
- Further research into neuropeptide involvement in viral keratitis is warranted.
