Universität zu Köln

Tran, Bao N., Maass, Martina, Musial, Gwen, Stern, Michael E., Gehlsen, Uta ORCID: 0000-0001-9057-9199 and Steven, Philipp ORCID: 0000-0001-6892-3619 (2022). Topical application of cannabinoid-ligands ameliorates experimental dry-eye disease. Ocul. Surf., 23. S. 131 - 140. AMSTERDAM: ELSEVIER. ISSN 1937-5913

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Abstract

Purpose: Dry eye disease (DED) is a multifactorial disease, with limitations regarding efficacy and tolerability of applied substances. Among several candidates, the endocannabinoid system with its receptors (CB1R and CB2R) were reported to modulate inflammation, wound healing and pain, which are also core DED pathomechanisms. This study is to investigate the therapeutic responses of Delta-9 tetrahydrocannabinol (a non-selective agonist) and two selective antagonists, SR141716A (CB1R antagonist) and SR144528 (CB2R antagonist), as a topical application using a DED mouse model. Method: Experimental DED was induced in naive C57BL/6 mice. Expression of CBR at the ocular surface of naive and DED mice was determined by qPCR and in-situ hybridization. Either THC or CBR antagonists were compounded in an aqueous solution and dosed during the induction of DED. Tear production, cornea sensitivity, and cornea fluorescence staining were tested. At the end of each experiment, corneas were stained with beta 3-tubulin for analysis of corneal nerve morphology. Conjunctiva was analyzed for CD4(+) and CD8(+) infiltration. Results: CB1R and CB2R are present at the ocular surface, and desiccating stress increased CBR expressions (p < 0.05). After 10 days of DED induction, treated groups demonstrated a reduced CBR expression in the cornea, which was concurrent with improvements in the DED phenotype including fluorescence staining & inflammation. Applying THC protected corneal nerve morphology, thus maintained corneal sensitivity and reduced CD4(+) T-cell infiltration. The CB1R antagonist maintained cornea sensitivity without changing nerve morphology. Conclusions: Endocannabinoid receptor modulation presents a potential multi-functional therapeutic approach for DED.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tran, Bao N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maass, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Musial, Gwen UNSPECIFIED UNSPECIFIED UNSPECIFIED Stern, Michael E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehlsen, Uta UNSPECIFIED orcid.org/0000-0001-9057-9199 UNSPECIFIED Steven, Philipp UNSPECIFIED orcid.org/0000-0001-6892-3619 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-662361
DOI:	10.1016/j.jtos.2021.12.008
Journal or Publication Title:	Ocul. Surf.
Volume:	23
Page Range:	S. 131 - 140
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1937-5913
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERFERON-GAMMA; CB1 RECEPTORS; CORNEAL PAIN; SUBSTANCE-P; RELEASE; ANTAGONIST; PATHOPHYSIOLOGY; ANANDAMIDE; EXPRESSION; MANAGEMENT Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66236