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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 [Mucosal Immunol] 2018 Jul; Vol. 11 (4), pp. 1138-1148. Date of Electronic Publication: 2018 Feb 14. - 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 <superscript>-/-</superscript> (TSP-1 <superscript>-/-</superscript> ) mouse model of dry eye compared to C57BL/6 wild-type (WT) mice. Neural innervation was reduced in TSP-1 <superscript>-/-</superscript> lacrimal glands compared to WT controls, whereas the number of blood vessels was increased. Intracellular Ca <superscript>2+</superscript> stores and the amount of lysosomes, mitochondria, and secretory granules, but not the endoplasmic reticulum, were reduced in TSP-1 <superscript>-/-</superscript> compared to WT acini at 12 weeks of age. Ex vivo high KCl-evoked secretion was decreased in TSP-1 <superscript>-/-</superscript> compared to WT lacrimal gland tissue pieces. The α <subscript>1D</subscript> -adrenergic agonist-stimulated response was increased in TSP-1 <superscript>-/-</superscript> at 4 and 24 weeks but decreased at 12 weeks, and the ATP and MeSATP-stimulated peak [Ca <superscript>2+</superscript> ] <subscript>i</subscript> responses 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 Ca <superscript>2+</superscript> stores. Through these effects the absence of TSP-1 leads to disruption of ocular surface homeostasis and development of dry eye.
- Subjects :
- Animals
Calcium Channels, L-Type metabolism
Calcium Signaling
Cells, Cultured
Disease Models, Animal
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurotransmitter Agents metabolism
Potassium Chloride metabolism
Thrombospondin 1 genetics
Dry Eye Syndromes immunology
Lacrimal Apparatus physiology
Leukocytes, Mononuclear immunology
Peripheral Nerves physiology
Thrombospondin 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 11
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 29445135
- Full Text :
- https://doi.org/10.1038/s41385-018-0002-y