ER-1 deficiency induces inflammation and lipid deposition in meibomian gland and lacrimal gland.

PURPOSE: To investigated the role of estrogen receptor-1 (ER-1) in maintaining homeostasis in ocular surface. METHODS: ER-1-knockout (ER-1KO) mice were studied at 4 months of age. The ocular surface was examined using a slit lamp. Histological alterations in the meibomian gland (MG) and lacrimal gland (LG) were observed with H&E staining. Protein levels of P-ERK, peroxisome proliferator-activated receptor gamma (PPAR-γ), p-NFκB-P65, IL-1ß, aquaporin 5 (AQP-5), fatty acid-binding protein 5 (Fabp5) and K10 were determined by immunofluorescence and Western blotting. Gene expressions of APO-F, APO-E, K10, ELOVL4, PPAR-γ, SCD-1, and SREBP1 were quantified by qPCR. Conjunctival (CJ) goblet cell alterations were detected by PAS staining. Lipid metabolism in MG and LG was assessed using LipidTox. Apoptosis in MG and LG was analyzed through the TUNEL assay. RESULTS: Both male and female ER-1KO mice demonstrated increased corneal fluorescence staining scores. MG showed abnormal lipid metabolism and ductal dilation. LG displayed lipid deposition and reduced AQP-5 expression. CJ experienced goblet cell loss. MG, LG exhibited signs of inflammation and apoptosis. CONCLUSION: ER1 is pivotal for ocular surface homeostasis in both genders of mice. ER1 deficiency induces inflammation and lipid deposition to MG and LG, culminating in dry eye-like manifestations on the ocular surface.

IL-37 Inhibits Inflammation of Lacrimal Gland in Dry Eye Mice via the IL-37-PTEN-NFκB Signaling Pathway.

PURPOSE: This study aims to investigate the role of Interleukin-37 (IL-37) in mouse models of dry eye. METHODS: Two murine models of dry eye were employed in this investigation. The evaluation of the anti-inflammatory impact of IL-37 (200 µl, 10 µg/ml) on dry eye mice involved intraperitoneal injections administered once daily for 7 days. Additionally, intraperitoneal injection of VO-Ohpic trihydrate (VO, 0.25 mg/kg) in dry eye mice was performed to investigate the role of PTEN in the IL-37 anti-inflammatory signaling pathway. Tear production was assessed using phenol red cotton thread, while corneal damage was examined through sodium fluorescein staining using a slit lamp. Histological alterations in the lacrimal gland were observed through H&E staining. PAS staining was used to assess conjunctival goblet cells. The levels of NFκB-P65, p-NFκB-P65, IL-1ß, IL-6, TNF-α, CD3, AQP5, α-SMA and PTEN proteins were determined via Western blotting or immunofluorescence. RESULTS: Following IL-37 treatment, both dry eye models exhibited reduced corneal fluorescence staining scores and enhanced tear production. In lacrimal gland, the expression of p-NFκB-P65, IL-1ß, IL-6, CD3 and TNF-α was diminished, while PTEN, AQP5, α-SMA expression increased after IL-37 treatment in both dry eye mice. However, the intraperitoneal injection of VO significantly attenuated the anti-inflammatory effect of IL-37 on dry eye mice. CONCLUSION: IL-37 emerges as an anti-inflammatory mediator within the lacrimal gland of dry eye mice, exerting its effects through the IL-37-PTEN-NFκB signaling pathway.