{"doi":"10.1016/j.exer.2025.110346","title":"Lysophosphatidic acid receptor 3 (LPAR3) regulates ocular surface chloride transport via calcium signaling","abstract":"Dry eye is a multifactorial disease associated with impaired tear film homeostasis, damaging the ocular surface epithelium. Lysophosphatidic acid receptors (LPARs) are G-protein coupled receptors involved in Ca 2+ and cAMP signaling via PLC and adenylyl cyclase activation. LPAR activation is involved in cell proliferation and wound healing in human corneal epithelial cells (HCECs) and in neuropathic pain. This study investigates the expression and functions of LPARs in ocular surface epithelial cells. Functional measurements of ocular surface potential difference (OSPD) were done in mice with topically applied, selective LPAR modulators. LPAR3 immunostaining was performed in mouse and human cornea and conjunctiva, and mouse lacrimal gland. LPAR-induced Ca 2+ signaling was studied in primary and immortalized HCECs. The general LPAR agonist, linoleoyl LPA, and the LPAR3 selective agonist, 2S-OMPT, stimulated ocular surface Cl − secretion via Ca 2+ -activated Cl − channels (CaCCs). LPAR3 was expressed in the corneal and conjunctival epithelia of mice and humans, as well as in mouse lacrimal gland. Activation of LPAR and LPAR3 in HCECs transiently elevated intracellular Ca 2+ through the G q /PLC signaling pathway. LPAR3 agonists may potentially have therapeutic efficacy in ocular surface diseases, including dry eye disease. • LPAR3 is expressed in mouse and human ocular surface epithelia and in mouse lacrimal gland ductal epithelia. • LPAR3 activation stimulates ocular surface chloride secretion in mice. • LPAR activation increases intracellular Ca 2+ in human corneal epithelial cells via the G q /PLC pathway.","journal":"Experimental Eye Research","year":2025,"id":538094,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1260756,"name":"Rongshan Yan","orcid":null,"position":1,"is_corresponding":false},{"id":672515,"name":"Yien–Ming Kuo","orcid":"0000-0001-9925-3013","position":2,"is_corresponding":false},{"id":1424241,"name":"Qi Gao","orcid":"0000-0001-5382-6891","position":3,"is_corresponding":false},{"id":1119941,"name":"Lívia de Souza Gonçalves","orcid":"0000-0003-4859-9078","position":4,"is_corresponding":false},{"id":1418723,"name":"Feeling Y. Chen","orcid":null,"position":5,"is_corresponding":false},{"id":516490,"name":"Matilda F. Chan","orcid":"0000-0001-8679-6932","position":6,"is_corresponding":false},{"id":1424736,"name":"Alan S. Verkman","orcid":null,"position":7,"is_corresponding":false},{"id":682302,"name":"Onur Çil","orcid":"0000-0001-5178-0199","position":8,"is_corresponding":false},{"id":368687,"name":"Neel D. Pasricha","orcid":"0000-0002-2327-5221","position":9,"is_corresponding":false},{"id":923188,"name":"Ethan S. Lindgren","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:52:16.891390Z","pmid":"40112945","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}