Purchase this article with an account.
Xiu Jun Song, De-Quan Li, William Farley, Li Hui Luo, Robert O. Heuckeroth, Jeffrey Milbrandt, Stephen C. Pflugfelder; Neurturin-Deficient Mice Develop Dry Eye and Keratoconjunctivitis Sicca. Invest. Ophthalmol. Vis. Sci. 2003;44(10):4223-4229. doi: 10.1167/iovs.02-1319.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN−/−) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN−/− mice.
methods. Determined by tail genomic DNA PCR, 25 NRTN−/− mice and 17 neurturin-normal (NRTN+/+) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1β was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR.
results. In comparison to that in age-matched NRTN+/+ mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN−/− mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN−/− mice were lower than in NRTN+/+ mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN−/− mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN−/− mice than NRTN+/+ mice. Tear fluid IL-1β and MMP-9 concentrations and the expression of IL-1β, TNF-α, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN−/− mice, compared with NRTN+/+ mice.
conclusions. Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.
This PDF is available to Subscribers Only