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Updated: Aug 7, 2026
Establishment of A Mouse Model of Aqueous Deficiency Dry Eye
Published on: November 1, 2024
Apical corneal barrier disruption in experimental murine dry eye is abrogated by methylprednisolone and doxycycline
Cintia S De Paiva1, Rosa M Corrales, Arturo L Villarreal
1Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Purpose:
To evaluate the mechanism of apical corneal epithelial barrier disruption in response to experimental ocular surface desiccation and the effects of two anti-inflammatory agents (methylprednisolone and doxycycline) on this process.
Methods:
Experimental dry eye (EDE) was created in C57BL/6 mice, without or with topical therapy, 1% methylprednisolone, 0.025% doxycycline, or physiologic saline solution (PSS) four times per day. Corneal smoothness and Oregon green dextran (OGD) permeability were assessed. Desquamation of and cornified envelope protein (involucrin and small proline-rich protein [SPRR]-2) expression by the corneal epithelium was evaluated by laser scanning confocal microscopy. Levels of cornified envelope proteins mRNA were measured by real-time PCR.
Results:
Corneal OGD permeability, surface irregularity, and the number of desquamating apical corneal epithelia significantly increased in EDE. Desiccating stress significantly increased expression of involucrin and SPRR-2 in the corneal epithelia. Treatment of EDE with methylprednisolone or doxycycline reduced corneal permeability to OGD, improved corneal smoothness, and decreased involucrin and SPRR-2 immunoreactivity compared with EDE+PSS.
Conclusions:
Disruption of apical corneal epithelial barrier function in dry eye is accompanied by increased apical desquamation and increased expression of cornified envelope proteins. Topical treatment of EDE with the anti-inflammatory agents methylprednisolone or doxycycline preserves apical corneal barrier function.
Insights
Experimental dry eye disrupts the corneal epithelial barrier, increasing desquamation and protein expression. Anti-inflammatory treatments like methylprednisolone and doxycycline preserve barrier function in dry eye models.
Area of Science:
- Ophthalmology
- Corneal Biology
- Dry Eye Disease Research
Background:
- The apical corneal epithelial barrier is crucial for ocular surface health.
- Dry eye disease (DED) involves disruption of this barrier, leading to discomfort and vision impairment.
- Understanding the mechanisms of barrier disruption and potential therapeutic interventions is vital for DED management.
Purpose of the Study:
- To investigate the cellular mechanisms underlying corneal epithelial barrier disruption in experimental dry eye (EDE).
- To assess the efficacy of topical methylprednisolone and doxycycline in mitigating barrier disruption in EDE.
- To evaluate the impact of these anti-inflammatory agents on epithelial desquamation and cornified envelope protein expression.
Main Methods:
- Experimental dry eye was induced in C57BL/6 mice.
- Mice received topical treatments of methylprednisolone, doxycycline, or saline solution.
- Corneal barrier function was assessed using Oregon green dextran (OGD) permeability and surface smoothness measurements.
- Epithelial desquamation and expression of cornified envelope proteins (involucrin, SPRR-2) were analyzed via confocal microscopy and real-time PCR.
Main Results:
- EDE significantly increased corneal OGD permeability, surface irregularity, and apical epithelial desquamation.
- Desiccating stress elevated the expression of involucrin and SPRR-2 in the corneal epithelium.
- Both methylprednisolone and doxycycline treatments effectively reduced OGD permeability, improved corneal smoothness, and decreased the expression of these proteins compared to saline treatment.
Conclusions:
- Corneal epithelial barrier disruption in dry eye is characterized by increased apical desquamation and cornified envelope protein expression.
- Topical anti-inflammatory agents, methylprednisolone and doxycycline, demonstrate a protective effect on the apical corneal barrier in experimental dry eye.
- These findings highlight the therapeutic potential of anti-inflammatory strategies in managing dry eye-associated barrier dysfunction.
