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Alteration in nerves and neurotransmitter stimulation of lacrimal gland secretion in the TSP-1−/−mouse model of aqueous deficiency dry eye
- Source :
- Mucosal Immunology; July 2018, Vol. 11 Issue: 4 p1138-1148, 11p
- Publication Year :
- 2018
-
Abstract
- The purpose of this study is to determine neural, vascular, protein secretion, and cellular signaling changes with disease progression in lacrimal glands of the thrombospondin-1−/−(TSP-1−/−) mouse model of dry eye compared to C57BL/6 wild-type (WT) mice. Neural innervation was reduced in TSP-1−/−lacrimal glands compared to WT controls, whereas the number of blood vessels was increased. Intracellular Ca2+stores and the amount of lysosomes, mitochondria, and secretory granules, but not the endoplasmic reticulum, were reduced in TSP-1−/−compared to WT acini at 12 weeks of age. Ex vivo high KCl-evoked secretion was decreased in TSP-1−/−compared to WT lacrimal gland tissue pieces. The α1D-adrenergic agonist-stimulated response was increased in TSP-1−/−at 4 and 24 weeks but decreased at 12 weeks, and the ATP and MeSATP-stimulated peak [Ca2+]iresponses were decreased at 24 weeks. These changes were observed prior to the appearance of mononuclear infiltrates. We conclude that in the lacrimal gland the absence of TSP-1: injures peripheral nerves; blocks efferent nerve activation; decreases protein secretion; and alters intracellular Ca2+stores. Through these effects the absence of TSP-1 leads to disruption of ocular surface homeostasis and development of dry eye.
Details
- Language :
- English
- ISSN :
- 19330219 and 19353456
- Volume :
- 11
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Mucosal Immunology
- Publication Type :
- Periodical
- Accession number :
- ejs44929442
- Full Text :
- https://doi.org/10.1038/s41385-018-0002-y