Dataset Information

Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

ABSTRACT: Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-?, Il-1?, Tnf-?), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease.

SUBMITTER: Marko CK

PROVIDER: S-EPMC3702735 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

Marko Christina K CK Menon Balaraj B BB Chen Gang G Whitsett Jeffrey A JA Clevers Hans H Gipson Ilene K IK

The American journal of pathology 20130510 1

Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjuncti ...[more]

PMID: 23665202

Similar Datasets

Project description:IntroductionDry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied.MethodsIn this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed.ResultsThe study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild.ConclusionsThis study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications.Trial registrationClinicalTrials.gov, NCT03688802.

Dataset Information

Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

Publications

Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets