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.
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.
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