Platelet Activating Factor Degradation in Tear Fluid from Guinea Pigs with Allergic Conjunctivitis

Kato, Masatomo; Mano, Hidetoshi; Ota, Atsutoshi; Konomi, Koji; Nakata, Katsuhiko

doi:10.1089/108076801750125757

Cited by 7 publications

(9 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it has been still unclear whether PAF plays a critical role in the pathophysiology of allergic conjunctivitis. To elucidate this question, we previously demonstrated that the levels of PAF metabolites such as lyso-PAF and 1-alkyl-2-acyl-sn-glycero-3-phosphocholine in tear samples are significantly increased in experimental allergic conjunctivitis in guinea pigs (13). This result agrees well with other studies demonstrating significant levels of PAF metabolites in allergic rhinitis both in rats and in humans (29).…”

Section: Discussionsupporting

confidence: 84%

See 1 more Smart Citation

The Role of Platelet Activating Factor and the Efficacy of Apafant Ophthalmic Solution in Experimental Allergic Conjunctivitis

Kato

Kurose

Oda

et al. 2003

Journal of Ocular Pharmacology and Therapeutics

Self Cite

View full text Add to dashboard Cite

Platelet-activating factor (PAF) may be an important mediator in allergic conjunctivitis. In this study, apafant, a potent PAF antagonist, was evaluated for topical ocular anti-PAF activity in PAF and antigen stimulated conjunctivitis models. PAF, when injected into parpebral conjunctiva, provoked an acute increase, measured as dye leakage, in conjunctival vascular permeability. Apafant inhibited this response in a dose-related manner, and the inhibitory action of 0.1% apafant lasted for at least 6 hours duration. PAF, when instilled into the conjunctival sac, induced itch-scratching behavior and clinical symptoms, such as conjunctival redness and edema. These were inhibited by pretreatment with apafant ophthalmic solution. In a passive conjunctival anaphylaxis model in guinea pigs, significant inhibition of the allergic response was observed following topical ocular administration of apafant 5 and 15 minutes prior to the antigen challenge. We have demonstrated that PAF plays an important role in the development of allergic conjunctivitis. These results clearly indicate that apafant has potential as a topical ocular anti-PAF for treating allergic conjunctivitis.

show abstract

Section: Discussionsupporting

confidence: 84%

“…Not PAF, but its metabolites (lyso-PAF and 1-alkyl-2-acyl-sn-glycero-3-phosphocholine) have been detected in tear fluids from guinea pigs with experimental allergic conjunctivitis (13). These results implicate PAF in allergic conjunctivitis and raise the possibility that PAF antagonists may be useful in the treatment of the disease.…”

Section: Introductionmentioning

confidence: 93%

The Role of Platelet Activating Factor and the Efficacy of Apafant Ophthalmic Solution in Experimental Allergic Conjunctivitis

Kato

Kurose

Oda

et al. 2003

Journal of Ocular Pharmacology and Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In support of this assumption, it has been reported that mast cells release PAF (20), and PAF, through its specific receptors, induces itch-scratching behavior and clinical symptoms such as conjunctival redness and edema (10). Furthermore, we have previously demonstrated that the levels of PAF metabolites such as lyso-PAF and 1-alkyl-2-acyl-snglycero-3-phosphocholine in tear samples are significantly increased in experimental allergic conjunctivitis in guinea pigs (17). At the second antigen challenge on Day 17, the guinea pigs are thought to be in a state of chronic allergic conjunctivitis because there are a large number of eosinophils in their conjunctiva (Fig.…”

Section: Discussionsupporting

confidence: 56%

Apafant, a Potent Platelet-Activating Factor Antagonist, Blocks Eosinophil Activation and Is Effective in the Chronic Phase of Experimental Allergic Conjunctivitis in Guinea Pigs

et al. 2004

Self Cite

View full text Add to dashboard Cite

Abstract. Platelet-activating factor (PAF) plays important roles in allergic reactions. In particular, there are many concerns about PAF, eosinophils, and the chronicity of allergic diseases. The purpose of the present studies is to elucidate the role of PAF in eosinophil activation at conjunctiva and to confirm the efficacy of Apafant (a potent PAF antagonist) ophthalmic solution in chronic experimental allergic conjunctivitis. Guinea pigs were actively immunized and allergic conjunctivitis was induced by repetitive instillation of 2.5% ovalbumin. PAF solution was topically applied and eosinophil activation was assessed by measuring the eosinophil peroxidase (EPO) activity in the tear fluid. Itch-scratching episodes and clinical symptoms scores were evaluated in the repetitive challenge conjunctivitis. From the instillation of PAF solution into guinea pig eyes, which were in a state of chronic allergic conjunctivitis, a significant increase in EPO activity was observed, and this increase was inhibited by pretreatment with Apafant. In the repetitive challenge model, the animals treated with Apafant ophthalmic solution showed a significant reduction of clinical symptoms and the itch-scratch response in both the first and the second challenges. PAF has an activity, that induces mediator release from eosinophils in the conjunctival tissues and may be involved in the chronic phase of allergic conjunctivitis.

show abstract

“…In this respect, insights into the role of platelet-activating factor (PAF) and PAF acetylhydrolase (AH) in regulating the conjunctival vascular permeability in allergic conjunctivitis were gained (35) and the relationship between the release of histamine and the production of prostaglandin I2 (PGD I 2 ) was examined (36).…”

Section: Guinea-pigsmentioning

confidence: 99%

Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

View full text Add to dashboard Cite

Numerous recent reports have demonstrated an increase in the prevalence and incidence of allergic conditions during the past years which affect approximately 25% of the general population (1) and about US$ 6 billion alone are estimated as direct costs of allergic rhinoconjunctivitis (2). Whereas a large amount of studies have focused on the pathophysiology of allergic rhinitis and asthma over the past years, ocular allergies are less well studied. However, allergic diseases affecting the eye are very common (3) and pediatric studies have shown that within distinct cohorts, up to 32% of allergic children have an ocular allergy as the primary manifestation of allergy (4). Allergic eye diseases such as allergic conjunctivitis commonly present with the symptoms of itchy, watery, red, sore and swollen eyes, but not pain (5).In contrast to the large amount of experimental studies on allergic asthma and the detailed knowledge that exists on mediators of allergic airway inflammation (6-8), there are few experimental studies using models of allergic eye diseases. Detailed reviews to assess the pathophysiology and immunology of ocular allergies have been limited. This review hopefully fills this void to provide the clinical and translational researcher in the area of ocular allergy. Pathophysiology of ocular allergiesBefore characterizing the different animal models of ocular allergy which have been established so far, it is crucial to reflect that within the area of ocular allergies, different disease entities exist and that only some of them may be mimicked by animal models. Formally, conjunctivitis may be divided into allergic and nonallergic conjunctivitis and the allergic form may also be subdivided into IgE-mediated and non-IgE-mediated allergic conjunctivitis ( Fig. 1) (9). Clinically, the spectrum of conjunctivitis types can be subdivided into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis and giant papillary conjunctivitis.In contrast to the other forms of conjunctivitis, allergic conjunctivitis is commonly based on an IgEmediated hypersensitivity reaction. Furthermore, allergic Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small numbe...

show abstract

Platelet Activating Factor Degradation in Tear Fluid from Guinea Pigs with Allergic Conjunctivitis

Cited by 7 publications

References 25 publications

The Role of Platelet Activating Factor and the Efficacy of Apafant Ophthalmic Solution in Experimental Allergic Conjunctivitis

The Role of Platelet Activating Factor and the Efficacy of Apafant Ophthalmic Solution in Experimental Allergic Conjunctivitis

Apafant, a Potent Platelet-Activating Factor Antagonist, Blocks Eosinophil Activation and Is Effective in the Chronic Phase of Experimental Allergic Conjunctivitis in Guinea Pigs

Animal models of allergic and inflammatory conjunctivitis

Contact Info

Product

Resources

About