Corneal enzymatic digestion resistance in the presence of oestradiol and oestradiol plus selective tissue oestrogenic activity regulators (STEAR).

Abstract

Objective: Elevated oestrogen levels and pharmacotherapies targeting oestrogen receptors can reduce corneal biomechanical stability, and altered stromal collagenase activity has been identified as one the possible mechanisms. We wished to determine the impact of oestradiol and the selective tissue (o)estrogenic activity regulator (STEAR), tibolone, on corneal enzymatic digestion resistance.

Methods and analysis: Freshly prepared ex vivo porcine corneas (n=48) were divided into three groups. Group A corneas served as untreated controls. Group B corneas were incubated in 20 µmol/L oestradiol solution and group C corneas were incubated in 20 µmol/L oestradiol solution with 2.5 mg tibolone before digestion in 0.3% collagenase-A solution to assess digestion time until corneal button dissolution.

Results: Group A control corneas showed the strongest resistance to collagenase digestion (31.38±2.03 hours). Corneas from group B that were preconditioned with oestradiol showed significantly lower resistance to digestion than group A control corneas (27.25±1.84 hours, p<0.01). Group C corneas that had been pretreated with both oestradiol and tibolone showed the least resistance to digestion (22.38±2.47 hours), with significant differences to group B (p<0.01) and group A (p<0.01).

Conclusion: Oestradiol significantly reduces corneal enzymatic digestion resistance. When combined with the STEAR, tibolone, there is a further decrease in stromal enzymatic digestion resistance. These results suggest that high oestradiol levels could have a significant impact on corneal conditions characterised by elevated collagenase activity, such as corneal ectasias (eg, keratoconus) and infectious keratitis. Importantly, the employment of STEAR therapy, such as tibolone, may amplify the effects of oestradiol.