INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model.
P2Y2 receptor agonists, like UTP and ATP, stimulate mucin secretion from goblet cells in vitro. Therefore, mucin stimulants could be good candidates for the treatment of dry eye syndrome because mucin increases the tear film stability and protects against desiccation of ocular surface. INS365 is a more stable P2Y2 receptor agonist than UTP. In the present study, we evaluated, in normal rabbit eyes, its effectiveness to release mucin from goblet cells and to protect the corneal damage induced by desiccation. For mucin secretion, impression cytology was performed following the instillation of INS365 solution or saline into the conjunctival sac. The specimens were stained with periodic acid and Schiff (PAS) reagent, and then the staining area was calculated using computer software. INS365 dose-dependently decreased the PAS staining area of conjunctival goblet cells from 2 to 15 min post-application. Furthermore, we utilized the rabbit short-term dry eye model to evaluate if INS365 eyedrops could protect against any of the damage produced by blockage of blinking with ocular speculum. INS365 significantly suppressed corneal damage at concentrations of more than 0.1% w/v. These results suggest that this P2Y2 agonist is a good candidate for the treatment of dry eye disease.
Fujihara
Tsutomu
T
Santen Pharmaceutical Co, Ltd Ophthalmic Division, Nara, Japan. fujiharat@santen.co.jp
Murakami
Tadahiro
T
Nagano
Takashi
T
Nakamura
Masatsugu
M
Nakata
Katsuhiko
K
D000818:Animals; D003890:Desiccation; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009077:Mucins / Q000378:metabolism*; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D011817:Rabbits; D013194:Staining and Labeling; D014500:Uracil Nucleotides
D009077:Mucins; D009883:Ophthalmic Solutions; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D014500:Uracil Nucleotides; C403315:diquafosol