| First Author | Bhattacharya S | Year | 2018 |
| Journal | Mucosal Immunol | Volume | 11 |
| Issue | 4 | Pages | 1138-1148 |
| PubMed ID | 29445135 | Mgi Jnum | J:344800 |
| Mgi Id | MGI:6765174 | Doi | 10.1038/s41385-018-0002-y |
| Citation | Bhattacharya S, et al. (2018) Alteration in nerves and neurotransmitter stimulation of lacrimal gland secretion in the TSP-1(-/-) mouse model of aqueous deficiency dry eye. Mucosal Immunol 11(4):1138-1148 |
| abstractText | 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 Ca(2+) 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 alpha1D-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 [Ca(2+)]i 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(2+) stores. Through these effects the absence of TSP-1 leads to disruption of ocular surface homeostasis and development of dry eye. |
