title: Topical interferon-gamma neutralization prevents conjunctival goblet cell loss in experimental murine dry eye.
abstract: Evidence suggests that the cytokine interferon (IFN)-γ released by natural killer and CD4(+) T cells contributes to the conjunctival goblet cell (GC) loss in dry eye. The purpose of this study was to investigate if topical neutralization of IFN-γ prevents or alleviates GC loss in an experimental desiccating stress (DS) model of dry eye. In this study, we found that topical IFN-γ neutralization significantly decreased DS-induced conjunctival GC loss. This was accompanied by decreased epithelial apoptosis, and increased IL-13 and decreased FoxA2 expression in the forniceal conjunctiva. To establish that IFN-γ produced by pathogenic CD4(+) T cells contributes to DS-induced GC loss, adoptive transfer of CD4(+) T cells isolated from DS exposed donors to naïve RAG-1(-/-) recipient mice was performed. Similar to the donor mice, topical IFN-γ neutralization decreased conjunctival GC loss, suppressed apoptosis and increased IL-13 expression in adoptive transfer recipients. In summary, this study demonstrated that topical neutralization of IFN-γ prevents GC loss via modulating apoptosis and maintaining IL-13 signaling.
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC505, Houston, TX 77030, USA; Shenyang He Eye Hospital, Shenyang, Liaoning, China.
authors: Xiaobo
authors: X
authors: Zhang
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC505, Houston, TX 77030, USA.
authors: Cintia S
authors: CS
authors: De Paiva
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC505, Houston, TX 77030, USA.
authors: Zhitao
authors: Z
authors: Su
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC505, Houston, TX 77030, USA.
authors: Eugene A
authors: EA
authors: Volpe
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC505, Houston, TX 77030, USA.
authors: De-Quan
authors: DQ
authors: Li
authors: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC505, Houston, TX 77030, USA. Electronic address: stevenp@bcm.edu.
authors: Stephen C
authors: SC
authors: Pflugfelder
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000096:biosynthesis; D007371:Interferon-gamma / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: C496503:Foxa2 protein, mouse; D051542:Hepatocyte Nuclear Factor 3-beta; D012313:RNA; D007371:Interferon-gamma
keywords: FOXA2; GC; IFN-γ; IL-13; KCS; MUC5AC; apoptosis; dry eye; gel forming mucin secreted by goblet cells; goblet cell; interferon gamma, a cytokine produced by natural killer (NK) and CD4(+) T cells; keratoconjunctivitis sicca