ArticleInvestigative ophthalmology & visual science2008
Small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia in dry eye disease.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
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- Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.Scientific reports · 2021Article
- Changes in tear protein profile in dogs with keratoconjunctivitis sicca following topical treatment using cyclosporine A.Veterinary world · 2021Article
- Alteration of gene expression in mice after glaucoma filtration surgery.Scientific reports · 2020Article
- PPAR-α Agonist Fenofibrate Suppressed the Formation of Ocular Surface Squamous Metaplasia Induced by Topical Benzalkonium Chloride.Investigative ophthalmology & visual science · 2020Article
- Article
- Deciphering Molecular and Phenotypic Changes Associated with Early Autoimmune Disease in the Aire-Deficient Mouse Model of Sjögren's Syndrome.International journal of molecular sciences · 2018Article
- Sleep deprivation disrupts the lacrimal system and induces dry eye disease.Experimental & molecular medicine · 2018Article
- Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeSquamous metaplasia occurs in ocular surface diseases like Sjögren's syndrome (SS). It is a phenotypic change whereby epithelial cells initiate synthesis of squamous cell-specific proteins such as small proline-rich protein 1B (SPRR1B) that result in pathologic keratin formation on the ocular surface. The authors hypothesized that inflammation is a key inducer of pathologic keratinization and that SPRR1B represents an analytical biomarker for the study of the molecular mechanisms.
methodsReal-time quantitative RT-PCR and immunohistochemistry were used to examine SPRR1B mRNA and protein in two different mouse models of dry eye and patients with SS. Adoptive transfer of mature lymphocytes from mice lacking the autoimmune regulator (aire) gene was performed to examine the role of inflammation as an inducer of squamous metaplasia. SPRR1B expression in response to several cytokines was examined in vitro, whereas the expression of cytokines IL1beta and IFNgamma was quantified in ocular tissues of aire-deficient mice and patients with SS.
resultsSPRR1B was increased across the ocular surface of mice with both desiccating stress and autoimmune-mediated, aqueous-deficient dry eye and in patients with SS. Adoptive transfer of CD4(+) T cells from aire-deficient mice to immunodeficient recipients caused advanced ocular surface keratinization. IL1alpha, IL1beta, IL6, IFNgamma, and TNFalpha induced SPRR1B expression in vitro and the local expression of IL1beta and IFNgamma was elevated in ocular tissues of patients with SS and aire-deficient mice.
conclusionsSPRR1B is a valid biomarker for the study of the molecular mechanisms of squamous metaplasia. There is a definitive link between inflammation and squamous metaplasia in autoimmune-mediated dry eye disease, with IL1beta and IFNgamma likely acting as key participants.
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