Development and evaluation of animal models for sex steroid deficient dry eye

Purpose: The present study was conducted to develop animal models to mimic postmenopausal/androgen deficiency dry eye and to evaluate the expression of sex steroid receptors (NR3A1, NR3A2 and NR3C4) in the ocular tissues of the developed models. Methods: The study was conducted in healthy Wistar rats of either sex weighing 180-250 g. Bilateral ovariectomy was performed in female rats and oral finasteride (dose of 1.16 mg/kg/day) challenge was given to both male and female rats. Along with time tear film stability was assessed by using cotton thread method and tear breakup time (TBUT). Dew point calculation was done using August-Roche-Magnus approximation during the tear assessments to correlate environmental factors affecting the tear function tests. At the end, animals were sacrificed and ocular tissues (lacrimal gland and cornea) were subjected for the quantification of the expression of NR3A1 (ER-alpha), NR3A2 (ER-beta) and androgen (NR3C4) receptors. Results: The impact of ovariectomy caused a significant tear film deficiency from the 20th day onwards in all female rats. The ten day finasteride administration also showed a significant tear film deficiency in both male and female rats. However, subjecting 60 days post ovariectomy rats to finasteride challenge did not show any further decrease in tear flow. Gene expression analysis also revealed a significant downregulation of sex steroid receptors in ocular tissues after ovariectomy and finasteride challenge. Discussion and conclusion: From this study, it has been concluded that ovariectomized and finasteride treated antiandrogenic models produced a significant tear deficiency in the rats which can be explored for pharmacological screening of topical agents and understanding the disease process in postmenopausal and androgen deficiency dry eye disorders. (C) 2014 Elsevier Inc. All rights reserved.