Comparison of the effects of different therapeutic agents on an experimental dry eye model in mice

Dry eye syndrome is a disease characterized with inflammation, tear film hyperosmolarity and instability, visual impairment, having the potential to damage ocular surface. It has been suggested that some risk factors including age, sex, environment, hormones, nutrition, some of the systemic and local effective drugs and refractive surgery may be responsible for its development. The disease has been reported to be more common in women, and the elderly in human and in dogs among animals.For the diagnosis of DES, in addition to clinical signs, some criteria, such as tear production, tear film stability, ocular surface impairment and some gross and cytological alterations on ocular surface are used. For treatment purpose, medical approaches, based on the criteria, i.e. relieve the clinical signs of the disease, remove factors effective on developing process of the disease, especially inflammation, or their combinations are administered. Base on this principle, this study purposed to be identified the most effective one comparing the therapeutic effects of some drugs commonly used for the treatment of this disorder.In the study, 112 BALB-C breed female mice were allocated equally and at random to two groups, control and experimental, which were divided in itself into 8 subgroups of 7 animal each. These subgroups were called as SF (Saline; 0.009%), SH (Sodium hyaluronate; 0.3%), DIK (Diclofenac sodium; 0.1%), PAT (Olopatadine; 0.1%), RET (Retinoic acid; 0.01%), FML (Fluoromethanole; 1%), CsA (Cyclosporine-A; 0.05%), DOK (Doxycycline 0.025%), and according to the agents administered. During 6 weeks of the study period, the experimental group animals were kept in a dry eye cabinet (DEC) (temperature; 21-25°C, relative humidity; < 30 %, flow rate; 15 L/min, flow speed; 2.3 ± 0.5 m/s) and control group animals in cages (relative humidity; 50-80%, temperature; 21-23 °C). While the animals of both groups received no agents between 0-2 weeks, it has been administrated to their right eyes the agents mentioned above twice a day and 5 ?l each time between 2-6 weeks.All experimental animals were evaluated considering the tests, blink rate, corneal fluorescein staining, break-up time (BUT), tear fluorescein clearance, impression cytology and corneal fluorescein permeability on the 0th, 2nd, 4th and 6th weeks of the study.When the control and experimental groups along with the subgroups were evaluated in terms of all parameters, it was determined that the difference between them was non-significant (P>0.05) except for BUT (P<0.05), whereas, this was significant (P<0.05) as to all parameters at the 2nd, 4th and 6th weeks.It was detected that in all experiment subgroup animals, blink rate and corneal staining scores were increased, but tear production and goblet cell counts, tear fluorescein clearance and BUT were decreased at the 2nd week as compared with the 0th week of the study.When the therapeutic actions of the agents were evaluated between the 2nd and 6th weeks or considering the subgroups variables, FML with regard to blink rate, PAT regarding to tear production rate, CsA according to corneal fluorescein staining, BUT and corneal fluorescein permeability tests and DIK in term of tear fluorescein clearance and impression cytology were determined as the most effective agents. When the result of all these parameters were assessed all together, the four week therapeutic actions of the agents from maximum to minimum could be arranged as CsA, DIK, FML, PAT, RET, SH, DOK and SF. The common and broad therapeutic actions of the first three agents indicate that the inflammation may play an important role on the pathogenesis of the disease. Thus, it suggests that anti-inflammatory drugs should always be taken into account during the treatment course of the DES.Key words: DES, Mouse, Evaporative Stress Factors, Treatment, Agent