Cyclosporine A eye drops inhibit the early-phase reaction in a type-I allergic conjunctivitis model in mice.
OBJECTIVE
The effects of cyclosporine A eye drops on the early-phase reaction were investigated in a type-I allergic conjunctivitis model.


METHODS
Mice were actively sensitized with ragweed (RW) absorbed on aluminium hydroxide gel and challenged with RW for 10 days (single challenge model) or 10-14 days (repetitive challenge model) after the first sensitization. For the evaluation of itching, ovalbumin was used as an antigen instead of RW. The effects of cyclosporine A eye drops on increased vascular permeability, mast cell degranulation, and itching were evaluated and compared with those of other anti-allergic eye drops.


RESULTS
In the single challenge model, cyclosporine A eye drops significantly inhibited the increase in vascular permeability and histological evaluations showed suppressed degranulation of mast cells. Disodium cromoglycate (DSCG) eye drops showed only a slight tendency to inhibit the increase in both pathophysiological parameters. Ketotifen or betamethasone eye drops significantly inhibited the increase in vascular permeability. The order of potency in the single challenge model was ketotifen > cyclosporine A > betamethasone. In the repetitive challenge model, cyclosporine A eye drops significantly inhibited the increase in vascular permeability and DSCG eye drops showed only slight inhibition. Ketotifen or betamethasone significantly inhibited the increase in vascular permeability. The order of potency in the repetitive challenge model was cyclosporine A > betamethasone > ketotifen. The effect of cyclosporine A eye drops on the itch-scratch response was studied. Cyclosporine A and DSCG significantly reduced the itch-scratch response in the single and repetitive challenge models; the effect of cyclosporine A in the repetitive challenge model was more potent than in the single challenge model.


CONCLUSIONS
Those results suggest that administration of cyclosporine A eye drops inhibit the early-phase reaction in type-I allergic conjunctivitis, which may be mediated by the suppression of mast cell degranulation. This action of cyclosporine A eye drops may be involved in the therapeutic effect of cyclosporine A on allergic conjunctivitis.
Shii
Daisuke
D
Research and Development Center, Santen Pharmaceutical Co. Ltd., Ikoma-shi, Nara, Japan. daisuke.shii@santen.co.jp
Oda
Tomoko
T
Shinomiya
Katsuhiko
K
Katsuta
Osamu
O
Nakamura
Masatsugu
M
D000287:Administration, Topical; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D001623:Betamethasone / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000276:immunology; D004205:Cromolyn Sodium / Q000494:pharmacology; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D010047:Ovalbumin / Q000276:immunology; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology
D018926:Anti-Allergic Agents; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D016572:Cyclosporine; D010047:Ovalbumin; D001623:Betamethasone; D004205:Cromolyn Sodium; D007665:Ketotifen