To investigate the effect of autophagy regulation on the progression of SS dry eye, PBS and the autophagy inhibitor CQ was treated in 13-week-old NOD-LtJ mice, the early SS stage, for 4 weeks by intraperitoneal injection. After 4 weeks of PBS and CQ administration, the mice were maintained without treatment for an additional 4 weeks and killed at 21 weeks to obtain blood, lacrimal gland, cornea, and conjunctiva samples (
Fig. 3A). As shown in
Fig. 3B, tear secretions were maintained from 17 to 21 weeks of age in CQ treatment groups, while the control group showed decrease of tear secretions according to age (21W PBS = 1.70 ± 0.07; 21W CQ = 2.48 ± 0.07,
P < 0.01). Corneal epithelial staining of NOD-LtJ mice was confirmed from the 13th week in the start of CQ administration and increased significantly at the 17th week in the control group (PBS). Corneal epithelial defects were not deteriorated in the CQ treatment group until the 21st week (
Fig. 3C). After 4 weeks of CQ treatment, at week 17, the corneal staining scores were significantly lower compared to the untreated control group (CQ = 1.75 ± 0.46; PBS = 2.38 ± 0.51,
P < 0.01). The effect of CQ treatment was maintained until 21 weeks (PBS = 2.62 ± 0.52; CQ = 1.88 ± 0.35,
P < 0.01). As shown in
Fig. 3D, goblet cell numbers in the conjunctiva of the control group at 21 weeks were 33.88 ± 7.64 and these numbers were significantly higher in the CQ treatment group (66.75 ± 8.87,
P < 0.01). Real-time RT PCR showed significantly decreased transcript levels of proinflammatory cytokines, IL-6, IL-1β, and TNF-α, in the cornea by the treatment of CQ. Also, the levels of matrix metallopeptidase 9 (MMP-9) in the cornea were attenuated by CQ treatment (
Fig. 3E). Similarly, in the LG, levels of IL-6, IL-1β, TNF-α, and MMP9 were comparatively lower in the CQ-treated group than in the PBS-treated control group (
P < 0.05). Serum anti-Ro antibody levels were also significantly lower in CQ treatment group at 21 weeks (
Fig. 3F,
P < 0.01).