Interferon-gamma deficiency protects against aging-related goblet cell loss.

Aging is a well-recognized risk factor for dry eye. Interferon-gamma (IFN-γ) has been implicated in conjunctival keratinization and goblet cell loss in dry eye. We investigated the role of IFN-γ in age-related dry eye by evaluating young (8 weeks) and aged (15 months; 15M) C57BL/6 (B6) and IFN-γKO mice.

Interferon-γ-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of Mucin Deficiency in Sjögren Syndrome.

Goblet cells (GCs) are specialized secretory cells that produce mucins and a variety of other proteins. Significant conjunctival GC loss occurs in both experimental dry eye models and patients with keratoconjunctivitis sicca due to the induction of interferon (IFN)-γ. With the use of a primary murine culture model, we found that GCs are highly sensitive to IFN-γ with significantly reduced proliferation and altered structure with low concentrations.

MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions.

Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1β and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID.

Differential Effects of Dexamethasone and Doxycycline on Inflammation and MMP Production in Murine Alkali-Burned Corneas Associated with Dry Eye.

Alkali burns to the cornea are among the most devastating injuries to the eye. The purpose of this study was to evaluate the effects of dexamethasone (Dex) or doxycycline (Doxy) on protease activity and corneal complications in a combined model (CM) of alkali burn and dry eye. C57BL/6 mice were subjected to the CM for 2 or 5 days (D).

Improvement of Outcome Measures of Dry Eye by a Novel Integrin Antagonist in the Murine Desiccating Stress Model.

Purpose: We investigated the effects of GW559090, a novel, competitive, and high-affinity α4 integrin antagonist, in a murine model of dry eye. Through interaction with vascular cell adhesion molecule 1 (VCAM-1) and fibronectin α4β1 integrin is involved in leukocyte trafficking and activation.

Methods: Female C57BL/6 mice, aged 6 to 8 weeks, were subjected to desiccating stress (DS).

Dexamethasone nanowafer as an effective therapy for dry eye disease.

Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves.

IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells.

Purpose: To investigate the effects of IL-13 on goblet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes.

Methods: Explants were excised from the conjunctiva of young C57BL/6 mice. Cultures received 200 μL per week of either Keratinocyte media (KSFM) or KSFM supplemented with 10 ng/mL IL-13 and were incubated for 3 (D3), 7 (D7), or 14 (D14) days.

An explanation for the central to peripheral thickness variation in the mouse cornea.

Background: The mouse corneal stroma varies in thickness across its diameter. The purpose of the present study was to explain this variation and to advance our understanding of stromal lamellar architecture in the mammalian cornea.

Methods: Eight C57BL/6 mice were killed, eyes enucleated, immersed in 2% glutaraldehyde fixative, processed and sectioned transversely for light and transmission electron microscopy.

Entrapment of conjunctival goblet cells by desiccation-induced cornification.

Purpose: To evaluate the effects of desiccating stress on conjunctival goblet cell density and morphology and the expression of cornified envelope precursors by the ocular surface epithelia.

Methods: Experimental dry eye (EDE) was created in C57BL/6 mice. Real-time PCR evaluated the expression of cornified envelope (CE) precursor proteins (involucrin and small proline-rich [Sprr] -1a, -1b, -2a, -2b, -2f, and -2g proteins), the cross-linking transglutaminase 1 enzyme (Tg-1) and Muc5AC mRNA transcripts by the ocular surface epithelia.

Ultraviolet radiation transmittance of the mouse eye and its individual media components.

Recently, the mouse has become the preferred animal model in ophthalmic research. Therefore, there is a need for enhanced understanding of the mouse eye to validate its use in different experimental setting. The purpose of this study was to determine the ocular transmittance of the whole mouse eye, the cornea and the crystalline lens, particularly in the ultraviolet radiation (UVR) wavebands.

Dimensions and morphology of the cornea in three strains of mice.

Purpose: To use a histologic approach to obtain dimensional and morphologic information on the cornea in three commonly used strains of mice.

Methods: Adult mice (three each of 129/SVJ, C57BL/6, and BALB/c) were euthanatized, and the eyes were enucleated, immersed in 2% glutaraldehyde fixative, and prepared for light and transmission electron microscopy. The full corneal, epithelial, stromal, and posterior limiting lamina (PLL) with endothelium thicknesses were measured at the same location centrally and peripherally.