Graduation Year
2025
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Partner Organization
University of California, San Francisco
Program Director
Patti Culross, MD, MPH
First Reader
Neel Pasricha, MD
Second Reader
Rongshan Yan
Abstract
Dry eye disease (DED) is a multifactorial disease that drives tear film instability and hyperosmolarity, directly damaging the ocular surface epithelium. Lysophosphatidic acid receptor (LPAR) is a G-protein coupled receptor (GPCR) responsible for Ca2+ and cAMP mobilization via PLC and adenylyl cyclase activation, respectively. LPAR signaling is involved in cell proliferation and wound healing in human corneal epithelial cells (HCECs) as well as in neuropathic pain. This study aims to investigate expression and functional roles of LPAR3 in ocular surface. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied LPAR modulators. LPAR3 immunostaining was performed in mouse and human cornea and conjunctiva and the mouse lacrimal gland. LPAR stimulated intracellular Ca2+ responses were studied in primary and immortalized HCECs. Topically administered LPAR general agonist (linoleoyl LPA) and LPAR3 selective agonist (2S-OMPT) stimulated Cl- secretion via Ca2+-activated Cl- channels (CaCCs). LPAR3 was expressed in corneal and conjunctival epithelia of mice and humans and the lacrimal gland of mice. Topical LPA eye drop reversed the tear volume decrease in a scopolamine injection acute desiccating stress mouse model. LPAR3 modulates ocular surface ion transport via intracellular Ca2+ elevation through the Gq/PLC pathway. Topical LPA may play a beneficial role in ocular surface homeostasis.
Comments
This research was also published in the article:
Lindgren ES, Yan R, Kuo YM, Gao Q, de Souza Goncalves L, Chen FY, Chan MF, Verkman AS, Cil O, Pasricha ND. Lysophosphatidic acid receptor 3 (LPAR3) regulates ocular surface chloride transport via calcium signaling. Exp Eye Res. 2025;255:110346.