Table 7.

Application of combined methods and experimental schedule in DED model.

Animal	Name of Chemical/Surgery	Environmental Condition/Other	Starting of Treatment	End of Experiment	References
C57BL/6 mice	Scopolamine hydrobromide (0.5 mg/0.2 mL) was injected subcutaneously in the dorsal skin of mice three times per day.	Exposed to a relative humidity < 25%, temperature of 20–22 °C, and airflow of 15 L/min, 24 h per day	-	On day 7 or 9	Lee et al. [75] 2017, Lee et al. [128] 2012
C57BL/6 mice	In brief, 0.5 mg/0.2 mL scopolamine hydrobromide was injected subcutaneously in the dorsal skin of mice three times daily.	The mice placed in the CEC were continuously exposed to a relative humidity < 30%, a constant temperature of 21–23 °C, and airflow of 15 L/min, 24 h a day	From day 3 to day 9, 2 µL of the topical agent was applied to both eyes of each mouse, twice a day (9:00 a.m. and 5:00 p.m.).	On day 9	Lee et al. [129] 2011
C57BL/6 mice	Topical application of atropine sulfate, 1%, twice daily for the first 48 h. In addition, the mice also received subcutaneous 0.1-mL injections of 5 mg/mL scopolamine hydrobromide three times a day (9:00 a.m., 1:00 p.m., and 5:00 p.m.) on their dorsal surface for the duration of the experiment.	Regulation of relative humidity <30%, <30%, a constant temperature of 21–23 °C, and airflow of 15 L/min, 24 h a day	48 h after the induction of dry eye, 3 µL of the topical formulatio nwas applied to both the eyes of the unanesthetized mice, twice a day (9:00 a.m. and 5:00 p.m.) from days 3 to 9.	9 days of treatment	Goyal et al. [130] 2009
C57BL/6 mice	Scopolamine was injected into the dorsal skin of mice (0.5 mg/0.2 mL at 9:00 a.m., 12:00 p.m., and 3:00 p.m.; 0.75 mg/0.3 mL at 6:00 p.m.).	Mice were placed in the controlled environmental chamber (relative humidity <30%, airflow 15 L/min, temperature 21–23 °C)	1 µL of eye drop was applied topically to the eye of an unanesthetized mouse once daily from 48 h to day 4 (total three doses) or day 9 (total eight doses).	On day 5 or 10 after treatment	Rashid et al. [131] 2008
C57BL/6 mice, and BALB/c	DS was induced by subcutaneous injection of scopolamine hydrobromide (0.5 mg/0.2 mL; four times a day (at 08:00 a.m., 12:00 p.m., 2:00 p.m., and 5:00 p.m.), alternating between the left and right flanks of 4–6-week-old mice	Mice were placed in a cage with a perforated plastic screen on one side to allow airflow from a fan (Cafrano) placed 6 inches in front of it for 16 h/day for 5 or 12 consecutive days; chamber (relative humidity 30–35%, airflow 15 L/min, temperature 80 °F)	–	On day 12	Niederkom et al. [132] 2006
129SvEv/CD-1 white mice	Subcutaneous injection of scopolamine (1 mg in 0.2 mL) three times daily in the flanks of 4–6-week-old 129SvEv/CD-1 white mice. Dry eye was induced in mice with a modification of a previously described technique.	Mice were exposed to a continuous air draft from a fan placed 15.24 cm in front of the cage in an environmentally controlled room (50% humidity, 18 °C) for 10 h a day for 12 consecutive days	–	On day 12	Yeh et al. [134] 2003
C57BL/6 and IFN- γ knockout mice	Subcutaneous injection of scopolamine hydrobromide (0.5 mg per 0.2 mL four times a day (8:00 a.m. 12:00 p.m., 2:00 p.m., and 5:00 p.m.), alternating flanks of mice	Humidity was maintained at 30–35% 16 h per day. DS was induced for either 5 or 10 consecutive days			De Paiva et al. [135] 2009
Male NOD.B10.H2b mice	0.5 mg/0.2 mL hypodermic injection of scopolamine hydrobromide into both hindquarters (one after the other) four times (9:00 a.m., 12:00 p.m., 3:00 p.m., and 6:00 p.m.) per day for 10 days	Desiccation stress was created by low ambient humidity (30–40%) using an air draft from a fan for 18 h per day	After the desiccation stress for 10 days, the scopolamine hydrobromide injections were discontinued, and the mice were placed in an environment of normal humidity and temperature. The eye drops, PBS, and 1 mg/mL or 5 mg/mL silk fibroin were administered five times (9:00 a.m., 11:00 a.m., 1:00 p.m., 3:00 p.m., and 5:00 p.m.) per day for 10 days	After 10 days of treatment	Kim et al. [122] 2017
New Zealand rabbits	Surgical dissection of nictitating membrane	After 1 week of surgery, animal were housed in controlled environment humidity, 22% ± 4%, air flow 3 to 4 m/s, and temperature 23 to 25 °C	–	After 3, 7, and 14 days	Chen et al. [133] 2021