Lacrimal Gland and Orbital Lesions in LatY136F Knock-in Mice, a Model for Human IgG4-Related Ophthalmic Disease.

PURPOSE: LatY136F knock-in mice were recently proposed as an animal model for immunoglobulin G4 (IgG4)-related disease. In this study, we investigated whether LatY136F knock-in mice exhibit ophthalmic lesions, specifically in the lacrimal and Harderian glands. METHODS: Lacrimal glands, Harderian glands, and adherent lymphoid follicle lesions were dissected from LatY136F knock-in mice and wild type (WT) C57BL/6 mice between 6 and 24 weeks of age. Tissues were stained with hematoxylin-eosin, immunoglobulin G (IgG), and anti-IgG1, a homologue of human IgG4, for histopathological analysis. RESULTS: In LatY136F knock-in mice, IgG1-positive cells infiltrated the space between the lacrimal gland acinar cells at 6, 9, 12, and 20 weeks or order, and the number of IgG1-positive cells did not differ significantly between these age groups. Infiltration of IgG1-positive inflammatory cell was also observed in the Harderian glands of LatY136F knock-in mice at all ages. The ratio of IgG1/IgG-positive cells averaged 80 and 67% in the lacrimal and Harderian glands, respectively. Dense IgG1-positive lesions were also seen in tissues adjacent to the lacrimal and Harderian glands in some LatY136F knock-in mice. In contrast, there were almost no IgG1-positive cell infiltrates in the lacrimal and Harderian glands of WT mice. CONCLUSION: IgG1-positive cells infiltrate the lacrimal and Harderian glands of LatY136F knock-in mice, indicating that LatY136F knock-in mice could be a representative animal model for IgG4-related ophthalmic disease.

Effect of inhalation anesthesia with isoflurane on circadian rhythm of murine intraocular pressure.

PURPOSE: For research on circadian intraocular pressure (IOP), rebound tonometers are widely used with or without general anesthesia as a non-invasive approach to obtain IOP values. However, whether general anesthesia such as inhalation anesthesia with isoflurane affects the circadian rhythm of IOP and in turn IOP measurements is currently unclear. As such, data reporting IOP values obtained under general anesthesia should be interpreted with caution. The purpose of this study was to evaluate how general anesthesia with isoflurane inhalation affects the circadian rhythm of IOP. METHODS: C57Bl/6J strain mice maintained using a 12h:12h light/dark cycle (lights on and off at ZT0 and ZT12, respectively) were used. IOPs were measured using a rebound tonometer (Icare TonoLab) before and 3, 5, 10, 15, and 30 min after initiating anesthesia in both light and dark phases (ZT 2-6 and ZT 14-18, respectively). Awake IOPs and IOPs at 3 and 5 min after anesthesia initiation were also obtained at ZT5, 8, 11, 14, 17, and 20 to assess IOP diurnal curves under gas anesthesia. RESULTS: IOP values gradually decreased after anesthesia initiation in both light and dark phases (P < 0.001) and there was no interaction between light/dark phase and anesthesia time (P = 0.88). There was a slight, but not significant, reduction in IOP 3 min after initiating anesthesia (P = 0.23), and significant decreases in IOP occurred at subsequent timepoints (P ≤ 0.001). Both awake and anesthetized mice showed a robust IOP rhythm that reached a peak and trough in the dark and light phase, respectively. Awake IOP levels did not significantly differ from those for anesthetized mice at 3 min after anesthesia initiation at all time points (P ≥ 0.07). CONCLUSIONS: Both awake and anesthetized mice demonstrated a robust circadian rhythm for IOP. Murine IOP showed similar gradual decreases under inhalation anesthesia with isoflurane in both the light and dark phases. IOPs measured using a rebound tonometer within 3 min of initiating isoflurane anesthesia were comparable to awake IOPs, and thus may be useful to monitor the circadian rhythm of IOP in mice.