prostaglandin-d2 and Conjunctivitis

The reactivity of ocular mast cells is poorly characterized in man. Provocation tests with codeine phosphate, a molecule known to activate connective tissue mast cells, were performed in ten normal subjects. Ten-fold increasing concentrations of codeine phosphate (10(-5) to 10(-1) mg/mL) were tested in both eyes until a positive challenge was observed. Schirmer strips were placed under the eyelid and left for five minutes. A negative control was performed ten days later. All subjects had a strongly positive reaction for the same codeine phosphate concentration (10(-1) mg/mL). Histamine was released in 8/10 subjects (control: 7.06 +/- 4.19 nM/L, codeine phosphate: 18.2 +/- 15.7 nM/L, P < .018), PGD2 was released in 8/10 subjects (control: 0 codeine phosphate: 273.3 +/- 408.9 ng/L). Disodium cromoglycate blocked the release of histamine and PGD2. Codeine phosphate is potent at causing mast cell activation in the eye and this effect is blocked by disodium cromoglycate.

Topics: Adult; Codeine; Conjunctiva; Conjunctivitis; Cromolyn Sodium; Histamine Release; Humans; Mast Cells; Prostaglandin D2

These studies demonstrate that the thromboxane (Tx) A2 mimetics U-46619, U-44069 and carbocyclic-TxA2 elicit a microvascular permeability response in the conjunctiva. U-46619 and U-44069 are among the most potent microvascular permeability factors described to date for the conjunctiva; their potency is exceeded only by that reported for leukotrienes D4 and E4. The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2-antagonists daltroban (BM 13505) and SQ 29548. Prostaglandin (PG) D2 also increased conjunctival microvascular permeability, but was less potent than U-46619 and far less susceptible to pretreatment with daltroban or SQ 29548. PGE2, PGF2 alpha and the prostacyclin analog carbocyclin did not increase conjunctival microvascular permeability. It appears that the conjunctiva exhibits a unique microvascular permeability response to TxA2-mimetics: this view is experimentally supported by the absence of a cutaneous microvascular permeability response to U-46619, U-44069 and carbocyclic-TxA2.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Capillary Permeability; Conjunctiva; Conjunctivitis; Fatty Acids, Unsaturated; Guinea Pigs; Hydrazines; Male; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Thromboxane A2

Prostaglandin D2 is a secondary mast cell mediator that causes redness, chemosis, mucous discharge, and eosinophil chemotaxis in the eye. It may play an important role in allergic ocular disease. Although histamine is a key mediator of allergic inflammation, antihistamine therapy provides only symptomatic relief. We added aspirin therapy to the treatment regimen of three patients with vernal conjunctivitis. Aspirin acetylates the enzyme cyclooxygenase, thereby preventing the formation of prostaglandin D2. Within two weeks after initiation of aspirin therapy, we noted dramatic improvement in conjunctival and episcleral redness and resolution of keratitis and limbal infiltration. We recommend a trial of oral aspirin as adjunctive therapy for intractable cases of vernal conjunctivitis.

Topics: Adolescent; Aspirin; Child; Conjunctivitis; Female; Histamine; Humans; Hypersensitivity; Male; Mast Cells; Prostaglandin D2; Prostaglandins D; Seasons; Urticaria Pigmentosa