Cyclosporine A Eye Drops Inhibit the Early-Phase Reaction in a Type-I Allergic Conjunctivitis Model in Mice

Shii, Daisuke; Oda, Tomoko; Shinomiya, Katsuhiko; Katsuta, Osamu; Nakamura, Masatsugu

doi:10.1089/jop.2009.0009

Cited by 9 publications

(3 citation statements)

References 21 publications

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“…This was consistent with our report that showed that the instillation of CyA eye drops 1 h before antigen challenge did not inhibit an early phase reaction in a murine allergic conjunctivitis model. 18) We also reported that instillation of CyA eye drops at 1, 4 and 7 h after antigen-challenge inhibited eosinophil infiltration into conjunctiva in a murine allergic conjunctivitis model. 19) Therefore, it is suggested that the effects of CyA on the late phase reaction are not mediated by suppressing the early phase reaction.…”

Section: Discussionmentioning

confidence: 69%

Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

Shii

Nakagawa

Yoshimi

et al. 2010

Biological & Pharmaceutical Bulletin

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Cyclosporine A (CyA) is a cyclic polypeptide calcineurin inhibitor that was first purified in the 1970s by Novartis Pharma (formerly Sandoz Pharma, Switzerland) from cultures of the fungus Tolypocladium inflatum. It has long been a trusted agent for suppressing not only graft rejection after transplantation, but also immune reaction disorders often observed in autoimmune diseases. The therapeutic effects of CyA eye drops in the treatment of vernal keratoconjunctivitis (VKC), one of the most severe refractory allergic conjunctival diseases, have been described in several studies. [1][2][3] VKC involves severe allergic inflammation sufficient to cause the formation of proliferative conjunctival giant papillae, hyperemia, edema, swelling, mucous discharge and corneal damage. It has been reported that the infiltration of inflammatory cells such as mast cells, eosinophils, neutrophils, and T cells were detected in the papillae of VKC patients. [4][5][6][7][8] Therefore, in addition to immunoglobulin E (IgE)-mediated allergy induced by mast cells, a late phase reaction mediated by eosinophils and delayed-type allergy induced by T cells are thought to be involved in VKC induction.Fukushima et al. reported the inhibitory effect of CyA eye drops on eosinophil infiltration in a mouse allergic conjunctivitis model. 9) We have also reported that the instillation of CyA inhibited neutrophil infiltration into the conjunctiva in a delayed-type allergic conjunctivitis model in guinea pigs. 10)However, the efficacy of CyA eye drops in treating the symptoms in these allergic conjunctivitis models has not been previously reported. Therefore, to understand how CyA works in VKC therapy, we investigated the effects of CyA eye drops on ocular symptoms in late phase and delayed-type allergic conjunctivitis models in guinea pigs. Animals Five-week-old male guinea pigs (Hartley, Nippon SLC, Shizuoka, Japan) were housed under a 12-h light-12-h dark cycle (07:00-19:00 h), with room temperature maintained at 23Ϯ3°C and humidity at 50Ϯ20%. Food and water were given ad libitum. All experiments were performed in accordance with the Association for Research in Vision and Ophthalmology statement for the Use of Animals in Ophthalmic and Vision Research and approved by the Santen Institutional Animal Care and Use Committee. MATERIALS AND METHODS ReagentsInduction of Late Phase Reaction in the Allergic Conjunctivitis Model Allergic conjunctivitis was induced using the method of Sengoku et al.,11) with some modification. OVA solution (40 mg/ml dissolved in saline) was emulsified with an equal volume of FCA. Then, 1 ml of the mixture was intraperitoneally injected into guinea pigs on days 0 and 7. Twenty-four days after the first immunization, 10 ml of 15% OVA solution was applied topically to the right eye to elicit an allergic reaction. Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis ModelsDaisuke SHII,* Shizu NAKAGAWA, Miwa YOSHIMI, Osamu KATSUTA, Tomoko ODA, and Masat...

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Section: Discussionmentioning

confidence: 69%

Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

Shii

Nakagawa

Yoshimi

et al. 2010

Biological & Pharmaceutical Bulletin

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“…One study showed that applying a solution of ovalbumin onto the ocular surface elicited hind-paw scratching in sensitized BALB/c mice, whereas application of a ragweed pollen suspension did not. 93) We found that a subconjunctival injection of an extract of ragweed pollen elicited hind-paw scratching in ICR mice that had been immunized with ragweed pollen in combination with an aluminum hydroxide adjuvant, but not in mice immunized with ragweed pollen alone. 94) In contrast to mosquito bite allergy, pollen allergy-induced scratching was almost completely abolished by mast-cell deficiency.…”

Section: Pollen Allergymentioning

confidence: 80%

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Kuraishi

2015

Biological & Pharmaceutical Bulletin

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Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was thought to be a key itch mediator. However, histamine and mast-cell degranulation were reported not to elicit scratching in animals. It was difficult to investigate the pathophysiology of itching and to evaluate the antipruritic efficacy of chemical agents in the early 1990 s. We showed that hind-paw scratching and biting were elicited by stimulation with pruritogenic agents in mice. Those results demonstrated for the first time that cutaneous itching could be evaluated behaviorally in animals. We established various animal models of pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell histamine did not play a key role in itching in any animal model examined except for the pollen allergy model. Histamine is not an exclusive itch mediator of mast cells; tryptase and leukotriene B 4 released from mast cells also act as itch mediators. Epidermal keratinocytes release several itch mediators, such as leukotriene B 4 , sphingosylphosphorylcholine, thromboxane A 2 , nociceptin, nitric oxide, and histamine, which may play important roles in pathological itching. Appropriate animal models of pathological itching are needed for pharmacological evaluation of the antipruritic efficacy of chemical agents.

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“…The results indicated no significant differences in ocular responses between the treatment and control groups (Figure D). No scratching behavior was observed in mice, and histological examinations with H&E staining showed no abnormalities (Figure E). These findings suggested that Th20 possessed good biocompatibility in the ocular region, supporting its potential for further research in drug delivery applications.…”

Section: Resultsmentioning

confidence: 96%

Noninvasive Framework Nucleic Acid Eye Drops for Retinal Administration

Zhu,

Yan,

Wang

et al. 2023

ACS Appl. Bio Mater.

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Intravitreal injection is widely employed for the treatment of retinal diseases. However, it suffers from various drawbacks, including ocular trauma, risk of infection, and poor patient compliance due to frequent administrations. Due to the presence of barriers such as the cornea, it has been a challenge to develop efficient noninvasive ophthalmic eye drops that can reach the retina. Framework nucleic acids (FNAs), known for their excellent biocompatibility and precise, controllable shape and size, have been extensively utilized in drug delivery application. Here, we report the development of size- and shape-resolved fluorescent DNA frameworks for noninvasive retinal administration. Results show that tetrahedral DNA nanostructures (TDNs) with an edge length of 20 bp can reach the retina within 6 h with the highest efficiency. Moreover, this delivery method exhibits excellent biocompatibility. Our findings provide an approach for the development of localized treatment strategies for retinal diseases using FNA-based nanocarriers.

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Cyclosporine A Eye Drops Inhibit the Early-Phase Reaction in a Type-I Allergic Conjunctivitis Model in Mice

Cited by 9 publications

References 21 publications

Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

Inhibitory Effects of Cyclosporine A Eye Drops on Symptoms in Late Phase and Delayed-Type Reactions in Allergic Conjunctivitis Models

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Noninvasive Framework Nucleic Acid Eye Drops for Retinal Administration

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