Dynamic observation of ocular surface in ovariectomized cynomolgus monkey

Objective

To investigate the feasibility of ovariectomized cynomolgus monkey as an animal model of postmenopausal dry eye.

Methods

Six healthy adult female cynomolgus monkeys (aged 4-6 years old) were selected.Cynomolgus monkeys were divided into ovariectomized group and sham operation group by random number table.Bilateral ovariectomy was performed in each cynomolgus of the ovariectomy group, and the same operation was operated in the sham group but the ovaries were not removed.The venous blood of the lower extremities of each cynomolgus monkey was collected before operation and at 1 month, 3 and 6 months after operation respectively.The concentrations of estradiol and testosterone were measured by radioimmunoassay.At the above time points, tear-liquid osmotic pressure detector 5600 was used to detect the tear osmotic pressure of cynomolgus monkeys in each group, and dry eye related examinations, including SchirmerⅠtest (SⅠt), corneal fluorescein staining and conjunctive impression cytology were performed.

Results

Preoperative and postoperative serum estradiol, testosterone concentrations in the ovariectomy group were lower than those in the sham operation group, but there were no significant differences between the two groups (F_group=5.16, P=0.09; F_group=1.46, P=0.29). There was no significant difference in the osmotic pressure between the two groups (F_group=0.83, P=0.37). The osmotic pressure in the 3 months after ovariectomy was higher than that in the 1 month after ovariectomy in the ovariectomy group, with a significant difference between them (t=5.12, P<0.05). There was no significant difference in SⅠt between ovariectomized group and sham operation group (F_group=0.06, P=0.82), the SⅠt in the 3 months after ovariectomy was lower than that in the 1 month after ovariectomy in the ovariectomy group, with a significant difference between them (t=1.13, P<0.05). There was no corneal fluorescein staining at each time points before and after ovariectomy in each group.The conjunctive impression cytology examination showed that, in the ovariectomy group, the morphology of conjunctival epithelial cells was normal, the number of conjunctival goblet cells was large, the periodic acid Schiff staining was purple before and 1 month after ovariectomy, which were similar to those in the sham operation group; three months after ovariectomy, the conjunctiva epithelial cell body was larger and had diverse forms, goblet cells were shrinked; six months after ovariectomy, the shapes of conjunctival epithelial cells were diverse and not easily been distinguished, the number of goblet cells was distinctly decreased.

Conclusions

The ocular conjunctival cells in the ovariectomized cynomolgus monkey have abnormal changes in morphology, and tear osmotic pressure increase, the ocular surface dynamic changes are consistent with the decrease of serum estrogen level, so ovariectomized cynomolgus monkeys can be used as sex hormone-related dry eye animal models.

Dry eye; Sex hormones; Ocular surface; Tears osmotic pressure; Conjunctival/cytology; Disease models, monkey