Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated topical applications of fluoresceinyl ovalbumin (FL-OA) to the conjunctival sac of guinea pigs sensitized them for conjunctival type 1 hypersensitivity reactions and mast cell degranulation. Guinea pigs infected with Ascaris suum, with high titers of circulating anti-A suum IgE and IgG1 antibody, also produced conjunctival type 1 reactions on topical challenge with A suum antigen. These reactions were no more intense than those of animals topically sensitized and challenged with FL-OA, which in some instances had no detectable serum homocytotropic antibody. Persistently reactive animals that had undergone repeated type 1 conjunctival reactions had histological findings (eg, papillary changes with extensive epithelial eosinophil infiltrates, epithelial thickening or thinning, numerous goblet cells, subepithelial lymphoid cell infiltrates, and new vessel formation) resembling those of human atopic vernal conjunctivitis.
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PMID:Vernal conjunctivitis. Model studies in guinea pigs immunized topically with fluoresceinyl ovalbumin. 649 52

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.
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PMID:Aspirin therapy in vernal conjunctivitis. 657 38

Immuno-histopathological studies of conjunctival tissue biopsied from patients with non-sight-threatening allergic conjunctivitis or with sight-threatening allergic keratoconjunctivitis should lead to more effective management of these eye conditions, based on the specific cellular involvement. The major difference between these two categories of eye disease was the occurrence of T-lymphocytes, which were absent in the former but prominent in the sight-threatening disorders. Seasonal and perennial allergic conjunctivitis both showed a heavy mast cell increase, due to infiltration of mucosal type mast cells, and allergen challenge studies linked mast cell histamine release to the early phase reaction occurring within 20 minutes. A second histamine peak at six hours after challenge might implicate basophils (or refractory mast cells) and was accompanied by a rise in eosinophil cationic protein. In sight-threatening, chronic allergic keratoconjunctivitis the responses were clearly directed by T-cells, themselves the primary effector cell in atopic keratoconjunctivitis, whereas vernal keratoconjunctivitis displayed a T-cell driven eosinophilia, with increased expression of the adhesion molecules involved in tissue invasion by these cells. Appropriate therapies for each different category of conjunctivitis should be based on the specific immunopathology, and directed at the activated cell types that are primarily responsible for the disease process.
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PMID:Therapeutic considerations: symptoms, cells and mediators. 754 Mar 64

Allergic eye disease has a variety of clinical manifestations including seasonal atopic conjunctivitis (SAC), perennial atopic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), and atopic blepharoconjunctivitis (ABC). We have investigated the number, distribution and protease expression of mast cells in normal and diseased conjunctiva with the use of immunohistochemistry in water-miscible resin sections. The median mast cell densities in normal subjects were 17 mm-2 in the bulbar substantia propria and 9 mm-2 in tarsal substantia propria. Mast cells were absent from the normal conjunctival epithelium at both sites. Mast cell densities were increased in the bulbar substantia propria in SAC, AKC and ABC. Tarsal substantia propria showed a significant increase in mast cells in ABC and AKC disease states. Mast cells express a range of proteases which varies according to their anatomic site. Mast cells in connective tissue are described to contain tryptase, chymase, cathepsin-G and carboxypeptidase-A, whereas mucosal mast cells contain only tryptase. In the diseased conjunctiva there was a marked reduction in proteases other than tryptase in the intraepithelial mast cells. There were also significant reductions in protease expression other than tryptase in the bulbar substantia propria in AKC and ABC. There appear to be specific alterations in the distribution of mast cells in the sub-categories of allergic eye disease. The distinction between mucosal and connective tissue mast cell phenotypes is not clear-cut and may depend on the functional state of the mast cells in relation to the microenvironment.
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PMID:Mast cell distribution and neutral protease expression in acute and chronic allergic conjunctivitis. 772 24

In a primary healthcare facility, there are certain 'rules of thumb' that can be recommended for the diagnosis and treatment of conjunctivitis. The type of discharge is a crucial factor in the differential diagnosis and can also be a clue towards the management in primary care. It is important to identify whether the conjunctivitis is an isolated case or part of another disease, and if it is acute or chronic, and I would suggest taking a smear or culture sample whenever possible. When the aetiology is not clear, I would try antibiotics. If the patient is allergic, and an allergic conjunctivitis is suspected, the best management today is to use mast cell stabilisers, and combine these with conservative measures of frequent washings, and compresses. If the aetiology remains doubtful, or if there is no obvious improvement using these treatments, the patient should be re-evaluated and/or referred to an ophthalmologist or specialist eye centre. The use of corticosteroids for conjunctivitis should certainly be avoided in primary healthcare. Conjunctivitis is often self-limited and the drug-induced consequences of improper management can be far more devastating than the disease itself.
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PMID:Current practice: diagnosis and treatment in primary healthcare. 778 48

Seasonal allergic conjunctivitis is the only ocular disease to involve solely Type-1 hypersensitivity, the other main forms of ocular allergy--perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis--each having a more complex immunological basis and a chronic inflammatory component. Involvement of secondary inflammatory cells, particularly eosinophils, in addition to the mast cells resident in the conjunctival substantia propria, can lead to more serious corneal damage with vision-threatening potential. Thoughtful management of allergic conjunctivitis is needed in order to control the ocular inflammation without incurring steroid-induced side-effects, and patient education is also an important factor in maintaining optimal allergen avoidance, especially in the more severe and chronic cases. Laboratory models can be helpful in assessing the potential of new drugs, and SWR mice (topically sensitised and challenged with short ragweed) show clinical signs of allergic conjunctivitis, together with mast cell and eosinophil involvement, remarkably similar to the human pathophysiology. The antiinflammatory activity of both steroids and nedocromil sodium observed in this animal model supports therapeutic evidence of the usefulness of second-generation mast cell stabilising drugs in the treatment of ocular allergy.
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PMID:The pathophysiology of ocular allergy: current thinking. 778 49

Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low-water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses.
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PMID:Giant papillary conjunctivitis. 788 81

Tryptase is useful as a specific and accurate indicator of mast cell activation, whereas histamine, a mast cell's major mediator, also exists in basophils. The aim of this study is to investigate histamine and tryptase levels in allergic conjunctiva. We measured histamine and tryptase levels in conjunctival epithelial cell suspension of children with allergic conjunctivitis (AC) and vernal kerato-conjunctivitis (VKC), and controls, and we evaluated correlations with clinical observations. Both the histamine and tryptase levels in VKC were significantly higher than controls (p < 0.05, p < 0.01), and histamine levels in VKC was also greater than AC (p < 0.05). The histamine/tryptase (H/T) ratios were 0.03 +/- 0.04 in AC, 0.08 +/- 0.09 in VKC and 0.006 +/- 0.006 in controls. The H/T ratios in VKC were significantly higher than controls (p < 0.05) and AC (p < 0.05), and were also found to correlate with the superficial punctate keratopathy (SPK) score (r2 = 0.89). Analyzing the histamine and tryptase levels in conjunctival epithelium may be useful in evaluating the allergic ocular surface, especially in the cases with SPK, where the increase in the histamine levels is not accompanied by an increase in tryptase levels. This suggests an important role for inflammatory cells such as basophils infiltrating into the conjunctival epithelium in allergic reactions.
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PMID:Histamine and tryptase levels in allergic conjunctivitis and vernal keratoconjunctivitis. 792 35

The term ocular allergy encompasses a group of diseases in which there is a high frequency of atopy, ocular itching, stringy discharge and a papillary conjunctival reaction. Conditions confined to the lids and conjunctiva (e.g. seasonal allergic conjunctivitis) have a good prognosis but those involving the cornea may result in visual impairment (e.g. atopic keratoconjunctivitis). Mast cell and eosinophil mechanisms are important in al the ocular allergies, but T cell inflammation is prominent only in vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Therapy involves the use of antigen avoidance (where possible), nonspecific medical therapy (e.g. cold compresses, artificial tears), specific medical therapy and, in certain situations, immunotherapy and surgery. Topical antihistamines (often in combination with a vasoconstrictor) and oral antihistamines are widely used in perennial and seasonal conjunctivitis. Levocabastine is a new preparation which is more rapid and potent. Mast cell inhibitors [e.g. sodium cromoglycate (cromolyn sodium)] have a proven track record as safe and effective therapy for all ocular allergic diseases and the newer, more potent nedocromil and lodoxamide are now available. Topical steroids are only indicated in sight-threatening disease due to their serious adverse effects and other therapy should be continued to minimise the dose required. There is a lack of intermediate potency and high potency but safe topical preparations. A number of future possibilities exist, some of which have been partially explored. Cyclo-oxygenase inhibitors have proved of limited use, but inhibitors of lipoxygenase and kinin pathways are awaited. Although results with HEPP have been disappointing, other modulators of mast cell function (e.g. picumast, beta-agonists and phosphodiesterase inhibitors) may prove useful in the future. So far, results with topical cyclosporin in serious disease are very encouraging. Future developments in the manipulation of eosinophilic products, cytokines and adhesion molecules may also be relevant. However, the current situation for those with serious ocular allergy remains a disturbing dependence upon topical steroids, with all the attendant risks.
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PMID:Therapeutic options in ocular allergic disease. 852 55

A mouse model of conjunctivitis has been developed by topical application of compound 48/80 (C48/80), an agent that triggers mast cell degranulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/J mouse strains to C48/80 stimulation, and of a mutant strain with mast cell depletion (WBB6F1/J and its sham control). Conjunctivae were collected and examined histopathologically at 15 min and 1,6,24,48 and 72 h after topical C48/80 administration. Conjunctival inflammation developed in all strains, although the severity varied. The conjunctivitis was characterized clinically by irritation, discharge, erythema, and chemosis. Pathology showed conjunctival infiltration with neutrophils, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulation of mast cells and evacuation of goblet cells were also observed. Late-phase inflammatory reactions peaked 6-24 h after C48/80 administration and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conjunctival inflammatory response similar to allergen-induced conjunctivitis. The depletion of mast cells significantly reduced the inflammation. This model which consistently mimics the clinical signs and histopathological processes of allergic conjunctivitis in humans, is practical and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the allergic inflammatory cascade.
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PMID:Compound 48/80-induced conjunctivitis in the mouse: kinetics, susceptibility, and mechanism. 862 98


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