Abstract
Purpose :
Dry eye disease (DED), characterized by inadequate tear production, is a common disease affecting up to 6.8 percent of the adult US population. Leucine-rich repeat-containing protein 26 (LRRC26) is a regulatory subunit of the Ca2+ and voltage-activated K+ channel (BK channel) and localizes specifically to secretory epithelial cells within conjunctiva, salivary and lacrimal glands. LRRC26 causes the largest shift in BK gating even without any elevation of cytosolic Ca2+, supporting its role in normal secretory function. The purpose of this study was to determine the role of LRRC26 on tear production. Here, we show that tear production was reduced in LRRC26 knockout (KO) mice eye with significantly greater corneal fluorescein staining compared to age, gender-matched wildtype (WT) mice. LRRC26 KO mice maybe a valuable model to test drug candidates for dry eye disease.
Methods :
5 months old wild type and LRRC26 KO mice (WT n = 8, KO n = 6; Regeneron Pharmaceuticals Inc.) were used in this study. Tear production was measured using Schirmer's test strips (Showa Yakuhin Kako Co. LTD,Tokyo, Japan). One microliter 1% sodium fluorescein (Alcon Laboratories, Inc. Fort Worth, TX) was applied to the ocular surface, and corneal fluoresein staining was scored and quantified using a dissecting microscope (SMZ-1; Nikon, Tokyo, Japan).
Results :
Gene expression profiling in adult mice revealed that LRRC26 is highly expressed in saliva-secreting gland, cornea, conjunctiva, and trabecular meshwork. Strong LacZ staining was also observed in LRRC26 KO salivary gland. In LRRC26 KO mice, tear production was significant reduced (3.52 ± 0.26mm, n=12) compared to WT (6.28 ± 0.42mm, n=16. p< 0.00002). Ocular surface fluorescein staining was significantly increased in LRRC26 KO (4.54 ± 0.35, n=12) compared to WT controls (1.47 ± 0.17, n=16. p<0.00001). Corneal thinckness in LRRC26 KO was also slightly thinner (100.08 ±2.20 µm, n=12) than in age-matched WT mice (106.06 ± 1.57 µm, n=16. p<0.0314).
Conclusions :
Our results suggest that genetic deletion of LRRC26 gene in mice reduces tear production and increases corneal surface staining, reminiscient of dry eye condition. LRRC26 may play a role in dry eye desease and serves as a potential therapeutic target for DED.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.