Effect of long-term application of preservative free anti-glaucoma eye drops on ocular surface in mice

Abstract

Purpose : Direct effect of anti-glaucoma eye drops without preservatives on ocular surface has been debated. To investigate in vivo effect of preservative-free prostaglandin analogue and β-blockers applications on alteration of ocular surface using different murine models.

Methods : Eight-week-old female C57BL/6 mice (B6, n=20) received topical preservative-free latanoprost 0.005% or Phosphate-buffered saline (PBS) once a day for 5 weeks. Next, age and sex matched BALB/c mice (n=52) were used with topical application of preservative-free latanoprost 0.005%, tafluprost 0.0015%/timolol 0.5% or balanced salt solution (BSS) once a day for 5 weeks or without any treatment (negative control). Tear production and corneal staining scores were assessed. Real-time polymerase chain reaction (PCR) was applied to detect inflammatory cytokines, and expression of substance P, Calcitonin Gene-Related Peptide (CGRP), and nerve growth factor (NGF).

Results : Regardless of mouse model, corneal staining score significantly increased in both latanoprost and tafluprost/timolol combination. Only latanoprost application showed significant less tear secretion in BALB/c mice. In B6 mice, IL-1b and IL-6 significantly increased with latanoprost application whereas, IFN-r, IL-17a, and TNF-a did not show any differences. In BALB/C mice, IL-1b and IL-6 did not increase in both latanoprost and tafluprost/timolol combination. Substance P significantly elevated in both latanoprost and tafluprost/timolol combination, and CGRP significantly decreased in tafluprost/timolol combination compared with negative control.

Conclusions : Long-term use of topical preservative-free anti-glaucoma drugs affect to disrupt ocular surface regardless of mouse model, which may be related to either neurogenic or inflammatory responses. Given that inflammatory outcome is different, the effect of the mouse strain should be considered to elucidate immune reaction of anti-glaucoma eyedrops.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.