Abstract
Purpose :
Prostaglandin analogues are recommended as a first choice for the treatment of ocular hypertension and open-angle glaucoma due to their strong intraocular pressure (IOP)-lowering effects, however, they in some patients cause local side effects (PAP, prostaglandin associated periorbitopathy) including eyelash growth, pigmentation of iris and skin around the eye and deepening of the upper eyelid. Prostaglandin analogues activate their specific receptors, such as FP and prostamide receptors. Therefore, it is considered that their side effects are caused through mediating their own specific receptors. We are developing omidenepag isopropyl (OMDI), a selective EP2 receptor agonist with non-prostaglandin structure, as a new IOP-lowering topical agent. Here we examined the effects of OMDI on eyelash growth, as compared with bimatoprost, through repeated transdermal administration in mice.
Methods :
Four-week-old female mice (C57BL 6J) were divided into three groups (n=10 in each) and received 3 μL of 0.003% OMDI solution, vehicle (negative control) or 0.03% bimatoprost (positive control) on upper eyelids of the right eyes once daily for 14 days. On the 15th day, all animals were euthanized, and upper eyelids with eyelashes were fixed with 10% neutral formalin for the evaluation of the number, length (short, middle and long) and thickness of eyelashes. The specimens prepared by sectioning paraffin-embedded tissue and staining with Hematoxylin-Eosin stain were microscopically examined to assess the eyelash morphology and its growth cycle in each group.
Results :
The number of eyelashes (143.5 ± 6.7 /eyelid), the eyelash thickness and the percentage of dermal papilla in anagen phase in OMDI group were similar to the vehicle group (144.2 ± 5.7 /eyelid). On the other hand, in bimatoprost group, the number of eyelashes (166.7 ± 7.0 /eyelid), eyelash thickness and the percentage of dermal papilla in anagen phase were significantly increased compared with those in vehicle group.
Conclusions :
These data indicated that OMDI did not promote the eyelash growth in mice while bimatoprost did, suggesting that OMDI is expected to be an anti-glaucoma ophthalmic solution that has no eyelash growth concern unlike existing prostaglandin analogues.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.