Inhibitory effect of the water-soluble retinoid X receptor partial agonist CAt-PMN on allergic conjunctivitis-like...

Allergic conjunctivitis (AC) is an immune-mediated inflammatory disease of the conjunctiva characterized by ocular itching, hyperaemia, and edema, and inflammatory cell infiltration. Though topical glucocorticoids (steroidal anti-inflammatory drugs) are effective for a broad range of signs and symptoms of ocular inflammation, their use is limited by potential adverse effects, including elevated intraocular pressure (IOP). Therefore, steroidal sparing-therapeutic approachs for AC are needed. Here we report a therapeutic effect of CAt-PMN, the highly water-soluble retinoid X receptor (RXR) partial agonist, in a mouse model of AC. ICR mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 5, followed by topical OVA challenge once a daily from day 14 to day 28. Betamethasone (0.1% w/v) or CAt-PMN (0.0035 or 0.035% w/v) was instilled into both eyes before each topical OVA challende. Repeated topical administration of CAt-PMN suppressed eye scratching behavior, allergic-like clinical symptoms, and eosinophils infiltration of into tears in a dose dependent manner. In a separate repeated-dose IOP study using C57BL/6 mice, topical dexamethasone at 1 μM induced a marked IOP elevation, whereas topical CAt-PMN at 1 μM did not under the conditions tested. These findings suggest that CAt-PMN may be a promising steroid-sparing therapeutic candidate for AC, although further studies using the same mouse strain and detailed ocular pharmacokinetic and safety evaluations are warranted.