Conjunctival Mast Cells Research Articles

Eyelid and conjunctival mast cell tumors: A retrospective study of 26 dogs and 8 cats.

The objective of the study was to describe clinical and histologic characteristics of eyelid (LMCT) and conjunctival (CMCT) mast cell tumors in dogs and cats presented to a referral clinic in Germany. Medical records were reviewed to identify dogs and cats diagnosed with LMCTs or CMCTs between 2006 and 2020. LMCT were diagnosed in 31 patients and were cutaneous (n = 28; 20 dogs and 8 cats) or subcutaneous (three dogs). Five cases involved the mucocutaneous junction (four dogs, one cat). CMCTs occurred only in dogs (n = 3). At the time of presentation two of the four canine LMCT cases involving the mucocutaneous junction had metastasized to a mandibular lymph node. When applying the Kiupel system, both these cases were categorized as high grade. 85.7% (18/21) of the canine (19 cutaneous and 2 subcutaneous) LMCT and all CMCT cases were categorized as Kiupel low grade. No local recurrences occurred in all LMCT cases in which clean surgical margins were obtained (n = 18, mean surgical margin width: dogs 9.4 mm, cats 3.8 mm). Two cats (2/4) and four dogs (4/7) with questionable or incomplete surgical margins experienced local recurrences (mean time to recurrence of 180 and 637 days in dogs and cats, respectively). Recurrence of low-grade LMCTs and CMCTs following excision with clean margins is rare. Tumors involving the mucocutaneous junction may be of higher grade and prone to lymphatic metastasis.

Development in therapeutic strategies for allergic conjunctivitis

Conjunctivitis, also known as pink eye, is a conjunctival inflammation. It is brought on by bacteria, viruses, toxins, and allergies, including coronaviruses, the most frequent reason being allergic conjunctivitis (AC), which is brought on by exposure to pollutants like pollen, animal hair, or mold. The primary contributor to it is the linkage of immunoglobulin E caused by allergens and receptors on stimulated conjunctival mast cells. As a consequence, mast cells are degranulated, along with the release of histamine, cytokines, chemokines, and lipid mediators. The particular eye tissues impacted and the immune mechanism(s) (both local and systemic) that are involved all play a role in the clinical course, length, intensity, and co-morbidities. It frequently occurs in conjunction with allergic rhinitis, also known as allergic rhino-conjunctivitis and other allergy conditions. Atopic keratoconjunctivitis, giant papillary conjunctivitis, seasonal and perennial conjunctivitis, and vernal keratoconjunctivitis are the different types of allergic conjunctivitis. Ocular allergies are frequently misdiagnosed and undertreated, despite the emergence of innovative therapeutic strategies. This review focuses on several previously published studies to discuss the available therapeutic options for treating allergic conjunctivitis as well as the potential targets for the therapies. The association of conjunctivitis with COVID-19, along with recent patents and research, has also been explored.

Therapeutic Targets in Allergic Conjunctivitis.

Allergic conjunctivitis (AC) is a common condition resulting from exposure to allergens such as pollen, animal dander, or mold. It is typically mediated by allergen-induced crosslinking of immunoglobulin E attached to receptors on primed conjunctival mast cells, which results in mast cell degranulation and histamine release, as well as the release of lipid mediators, cytokines, and chemokines. The clinical result is conjunctival hyperemia, tearing, intense itching, and chemosis. Refractory and chronic cases can result in ocular surface complications that may be vision threatening. Patients who experience even mild forms of this disease report an impact on their quality of life. Current treatment options range from non-pharmacologic therapies to ocular and systemic options. However, to adequately control AC, the use of multiple agents is often required. As such, a precise understanding of the immune mechanisms responsible for this ocular surface inflammation is needed to support ongoing research for potential therapeutic targets such as chemokine receptors, cytokine receptors, non-receptor tyrosine kinases, and integrins. This review utilized several published articles regarding the current therapeutic options to treat AC, as well as the pathological and immune mechanisms relevant to AC. This review will also focus on cellular and molecular targets in AC, with particular emphasis on potential therapeutic agents that can attenuate the pathology and immune mechanisms driven by cells, receptors, and molecules that participate in the immunopathogenesis and immunopathology of AC.

D451 CLINICAL ACTIVITY OF AK002, AN ANTI-SIGLEC-8 ANTIBODY, IN SEVERE ALLERGIC CONJUNCTIVITIS AND COMORBID ATOPIC DISEASES

Severe allergic conjunctivitis (AC) can lead to debilitating ocular symptoms with a risk of vision loss. Driven primarily by conjunctival mast cells and eosinophils, AC is also commonly associated with atopic conditions such as atopic dermatitis, asthma, and rhinitis. AC can present in various forms including atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), and perennial allergic conjunctivitis (PAC). AK002 is an anti-Siglec-8 antibody that selectively depletes eosinophils and inhibits mast cells. This open-label study is the first evaluation of the safety, tolerability, and efficacy of AK002 in AC.

Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis.

Molecules that are necessary for ocular hypersensitivity reactions include the receptors CCR1 and CCR3; CCL7 is a ligand for these receptors. Therefore, we explored the role of CCL7 in mast cell activity and motility in vitro and investigated the requirement for CCL7 in a murine model of IgE-mediated allergic conjunctivitis. For mast cells treated with IgE and Ag, the presence of CCL7 synergistically enhanced degranulation and calcium influx. CCL7 also induced chemotaxis in mast cells. CCL7-deficient bone marrow-derived mast cells showed decreased degranulation following IgE and Ag treatment compared with wild-type bone marrow-derived mast cells, but there was no difference in degranulation when cells were activated via an IgE-independent pathway. In vivo, CCL7 was upregulated in conjunctival tissue during an OVA-induced allergic response. Notably, the early-phase clinical symptoms in the conjunctiva after OVA challenge were significantly higher in OVA-sensitized wild-type mice than in control challenged wild-type mice; the increase was suppressed in CCL7-deficient mice. In the OVA-induced allergic response, the numbers of conjunctival mast cells were lower in CCL7-deficient mice than in wild-type mice. Our results demonstrate that CCL7 is required for maximal OVA-induced ocular anaphylaxis, mast cell recruitment in vivo, and maximal FcεRI-mediated mast cell activation in vitro. A better understanding of the role of CCL7 in mediating ocular hypersensitivity reactions will provide insights into mast cell function and novel treatments for allergic ocular diseases.

A histamine-independent itch pathway is required for allergic ocular itch

Non-histaminergic TRPA1 neural pathway is required for the development of allergic ocular itch. Pharmacological inhibition of TRPA1 channel can lead to novel therapeutic strategies to treat ocular itch in severe allergic conjunctivitis.

Nasal allergen deposition leads to conjunctival mast cell degranulation in allergic rhinoconjunctivitis.

The naso-ocular interaction in allergic rhinoconjunctivitis is well recognized from epidemiological, clinical, and experimental observations. The precise mechanisms remain incompletely understood. A new mouse model of allergic rhinoconjunctivitis was used to investigate the contribution of mast cells and trigeminal ganglia activation to conjunctival (conj.) inflammation after nasal allergen provocation. Sensitized mice were exposed to ovalbumin (OVA) via the nose and/or conjunctiva, and conj. homogenates were analyzed for histamine and substance P (using ELISA) and by eosinophil peroxidase (EPO) and beta-hexosaminidase assays. The conj. effects of nasal allergen deposition were compared with those induced by the mast cell activator C48/80 and with pretreatment of the mast cell stabilizer ketotifen or the transient receptor potential channel receptor (TRP) agonist capsaicin. Protachykinin 1 (TAC1) expression was quantified in the trigeminal ganglia using real time polymerase chain reaction. At 1 hour after nasal application of OVA, increased conj. levels of beta-hexosaminidase (0.68 ± 0.03 nm versus 0.56 ± 0.02 nm; p = 0.02), histamine (751.1 ± 52.17 ng/mL versus 546.3 ± 76.91 ng/mL; p = 0.05), and EPO (0.66 ± 0.09 nm versus 0.37 ± 0.03 nm; p = 0.02) were detected compared with saline. Higher levels of TAC1 expression were found in the trigeminal ganglia at 24 hours after OVA application (1326 ± 255 versus 687.5 ± 90.77 TAC1/beta-actin; p = 0.04). Nasal challenge with C48/80 increased substance P and beta-hexosaminidase levels in the conjunctiva, as well as TAC1 expression. Pretreatment with ketotifen resulted in lower levels of substance P as well as TAC1 expression. Destruction of sensory nerves in the nose by capsaicin reduced the OVA-induced conj. levels of substance P, histamine, and beta-hexosaminidase. Nasal allergen deposition in sensitized mice induced trigeminal TAC1 expression and conj. mast cell degranulation. These data represent a significant step forward in understanding the close interaction between nasal and conj. inflammation in allergy.

Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis.

Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivits, has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC mice. Th2-type cytokines, secreted phospholipase A2 type-IIA (sPLA2-IIA), and chemokines levels were also significantly diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific T-cell proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA2-IIA or eotaxin. Taken together, these findings demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and potential therapy for allergic diseases.

Immunomodulators for conjunctivitis

Allergic conjunctivitis is an IgE-mediated inflammatory of conjunctiva. Despite the fact that histamine is a major mediator in this condition, use of topical antihistamines often gives only temporarily relief. Therapeutic agents aiming at inflammatory cascades of the disease are desirable particularly in cases with prolonged and severe allergic conjunctivitis. The article reviews these new treatment armamentariums with regard to their mechanism of actions and clinical efficacy. Some second generation of antihistamines demonstrated anti-inflammatory properties such as inhibition of histamine release from mast cells as well as interference with the production cytokines and adhesion molecules from cord blood and conjunctival mast cells. Among these agents, ketotifen, epinastine and olopatadine are agents of major interest and are thus reviewed. Cromolyn, nedocromil, topical corticosteroids and immunotherapy, especially sublingual immunotherapy, are among other modes of therapy examined. Finally, the review focuses on cyclosporine A and tacrolimus, immunomodulators that have been extensively studied in the therapy of severe conjunctivitis such as atopic and vernal keratoconjunctivitis with promising results. Several immunomodulatory options are currently available for treatment of allergic conjunctivitis. These therapeutic availabilities bring about a better therapeutic outcome for patients with allergic conjunctivitis, particularly those on the severe end of the spectrum.

Interaction Between Conjunctival Epithelial Cells and Mast Cells Induces CCL2 Expression and Piecemeal Degranulation in Mast Cells

Intraepithelial mast cells are observed in giant papillae tissue samples obtained from patients with atopic keratoconjunctivitis (AKC)/vernal keratoconjunctivitis (VKC). We examined the roles of interaction between the conjunctival epithelial cells and mast cells. The interaction between human mast cells and conjunctival epithelial cells (HCjE) was investigated using a coculture model. Protein array analysis, ELISA, and real-time PCR were performed to test the interaction. Tissue samples (n = 6) from giant papillae were resected for therapeutic purposes, and subjected to immunohistological analysis of CCL2 expression. Recombinant CCL2 (10 ng/mL) was reacted with the cultured human mast cells and ultrastructural analysis was performed. A ragweed (RW)-induced mouse experimental allergic conjunctivitis model was used to examine ccl2 mRNA expression and mast cell morphology. Protein array and real-time PCR analyses showed that CCL2 protein/mRNA expression was induced by mast cell-HCjE coculture. Upregulation of CCL2 mRNA was observed in mast cells, whereas in situ CCL2 expression was observed at the conjunctival epithelium of the giant papillae by immunohistochemistry. Ultrastructural analysis showed that recombinant CCL2 treatment induced piecemeal degranulation (PMD) in the mast cells. Ultrastructural analysis of tissues from the giant papillae showed PMD of mast cells within the conjunctival epithelial cells. The RW-induced experimental allergic conjunctivitis model showed increased ccl2 mRNA expression and PMD morphology in the conjunctivae. Mast cell-conjunctival epithelial cell interaction induces CCL2 expression and subsequent PMD.

The murine CCR3 receptor regulates both eosinophilia and hyperresponsiveness in IgE-mediated allergic conjunctivitis

Background/aimsAllergic conjunctivitis is characterised by early-phase clinical symptoms and late-phase inflammation in the conjunctiva. The role of different chemokine receptors in allergic conjunctivitis, especially during the early-phase reaction, is still...

Canine conjunctival mast cell tumors: a retrospective study

To describe signalment, clinical presentation, treatment, recurrence rate, and outcome of canine conjunctival mast cell tumors (MCTs). Retrospective study. Canine cases were selected from the Comparative Ocular Pathology Laboratory of Wisconsin, Eye Path Lab of the UK, and California Eye Care for Animals. Thirty-two canine patients were identified as having a MCT presumed to be arising primarily from the conjunctiva. Data were collected from pathology submission request forms; additional information was collected by means of a questionnaire distributed to the veterinary ophthalmologist or veterinarian who performed the surgery. Data collected included age, gender, breed, location of tumor, dimensions of tumor, duration and growth rate, additional diagnostics, surgical descriptions, adjunctive treatment, histologic description, special stains, number of recurrences, and final outcome. Thirty-two dogs with 33 conjunctival MCTs meeting search criteria were identified. All dogs underwent surgical excision as the primary treatment. Surgical margins were evaluated for 30 tumors and were reported as: incomplete margins in 25 cases, narrow in four cases and complete in one case. Histologic grade was provided for 33 of 33 MCTs and included 10 low (30%), 18 intermediate (55%) and five high-grade (15%) tumors. Follow up information was received for 25 dogs. Four died of unrelated causes, two had local recurrence, 15 were currently disease free (mean 21.4 months postoperatively) and four were reported to be disease free at the reported rechecks but were lost to long term follow up (mean 13 months postoperatively). No dogs in the study were identified that died of MCT related disease.

Comparison of effects of alcaftadine and olopatadine on conjunctival epithelium and eosinophil recruitment in a murine model of allergic conjunctivitis

Background:Antihistamines constitute the first line of therapy for allergic conjunctivitis, and are safe and effective in relieving the signs and symptoms of ocular allergy. Despite this, they are less effective than some other drugs in relieving delayed symptoms of allergic conjunctivitis. Recent evidence suggests that changes in the conjunctival epithelium may underlie aspects of delayed reactions. In this study we compared two antihistamines, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.Methods:Studies employed a modified conjunctival allergen challenge model. Sensitized mice were challenged with topical allergen with or without drug treatments. Treatment groups were assayed for acute-phase (15 minutes) and delayed-phase (24 hours) responses. Groups were scored for allergy symptoms (redness, itch, tearing, and edema) and for conjunctival mast cell numbers. Delayed-phase groups were also examined for eosinophil numbers and for tight junctional protein expression.Results:Olopatadine-treated and alcaftadine-treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase. In contrast, alcaftadine-treated animals had significantly lower conjunctival eosinophil infiltration than either controls or olopatadine-treated animals. Allergen challenge caused a significant decrease in expression of the junctional protein, ZO-1, and this decrease was prevented by alcaftadine but not by olopatadine.Conclusion:Alcaftadine displays therapeutic properties beyond its antihistamine action. These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression.

Olopatadine: a drug for allergic conjunctivitis targeting the mast cell

Importance of the field: Ocular allergic diseases are characterized by specific activation of conjunctival mast cells with subsequent release of preformed and newly formed mediators. Mast cells are thus the first therapeutic target of ocular anti-allergic treatments.Areas covered in this review: In this review, a Medline literature search was conducted on conjunctival mast cells, their role in ocular allergy and mast cell stabilization by ocular anti-allergic compounds.What the reader will gain: Olopatadine hydrochloride, a mast cell stabilizer and histamine receptor antagonist, has been shown to inhibit mast cell activation in an in vitro model of human mast cell culture, reducing histamine and TNF-α release and upregulating proinflammatory mediators in conjunctival epithelial cells. In the in vivo conjunctival allergen challenge (CAC) model in allergic subjects, combined with objective evaluations of tear mediators and cytology, olopatadine reduced histamine tear levels and all aspects of allergic inflammation, confirming the positive clinical effects observed in active allergic patients.Take home message: Mast cells play a central role in the pathogenesis of ocular allergy. The CAC model is ideal for assessing the mast cell stabilizing effects of anti-allergic compounds. This review of clinical studies demonstrates the superiority of olopatadine compared with other topical allergic drugs.

Critical role of IgE-dependent mast cell activation in a murine model of allergic conjunctivitis

Allergic conjunctivitis is characterized by allergen-specific IgE in the serum and infiltration of eosinophils into the conjunctiva. The role of IgE and mast cells in allergic conjunctivitis is largely unknown, however. We investigated the importance of conjunctival mast cells in a murine model of IgE-mediated allergic conjunctivitis. IgE-mediated allergic conjunctivitis was initiated in C57BL/6-Kit(+/+) wild-type mice, mast cell-deficient Kit(W-sh/W-sh) mice, and Kit(W-sh/W-sh) mice that had been subconjunctivally or systemically engrafted with bone marrow-derived, cultured mast cells (BMCMCs) from Kit(+/+) wild-type mice, and clinical symptoms and infiltration of eosinophil of the eyes were evaluated. Total numbers of mast cells in the conjunctiva were counted, and the phenotypes of these cells were characterized by means of immunostaining and PCR analysis of murine mast cell proteases. No mast cells were detected in the conjunctiva or eyelid dermis of adult Kit(W-sh/W-sh) mice. Subconjunctival injection of BMCMCs resulted in local mast cell reconstitution, with the numbers of reconstituted mast cells in the conjunctiva and eyelid dermis comparable with those observed in wild-type Kit(+/+) littermates. Reconstituted and naive conjunctival mast cells expressed proteases ascribed to connective tissue-type mast cells but not mucosal mast cells. Passive transfer of ragweed-specific IgE followed by antigen challenge resulted in both early-phase clinical symptoms and late-phase eosinophilic inflammation in Kit(+/+) mice. These responses, which were significantly decreased in Kit(W-sh/W-sh) mice, were restored on reconstitution of the conjunctival mast cell population. These results suggest a direct contribution of IgE-activated mast cells to both the early-phase reaction and late-phase inflammation during ocular allergy.

Blocking Mast Cell–Mediated Type I Hypersensitivity in Experimental Allergic Conjunctivitis by Monocyte Chemoattractant Protein-1/CCR2

To characterize the roles played by monocyte chemoattractant protein-1 and its preferential receptor CCR2 (MCP-1/CCL2) in acute allergic inflammation. The direct effects of MCP-1 were evaluated histologically after a subconjunctival injection of recombinant MCP-1 into naïve mice. The mice were sensitized to ragweed pollen, and allergic conjunctivitis was induced by an allergen challenge. The location of the induced MCP-1 was determined by immunohistochemistry. Anti-MCP-1 antibody and CCR2-specific antagonist, RS 504393, were used to determine whether an inhibition of MCP-1 or CCR2 signals would suppress the allergen-induced immediate hypersensitivity reaction. The effect of blocking CCR2 was tested in vitro with isolated mast cells from connective tissue, to evaluate the co-stimulatory signals mediated by CCR2 in mast cells directly. A subconjunctival injection of MCP-1 stimulated conjunctival mast cell degranulation and recruited monocytes/macrophages. In the allergic conjunctivitis model, the allergen-induced MCP-1 protein was located in the monocytes/macrophages in the substantia propria of the conjunctiva. Blocking MCP-1 significantly suppressed the allergen-induced clinical signs and mast cell degranulation without affecting the allergen-specific IgE, or the release of Th2 cytokine from the isolated draining lymph node cells. Inhibition of CCR2 similarly suppressed the acute inflammatory responses. Consistent with the outcome of the disease model, inhibition of CCR2 suppressed allergen-specific degranulation of IgE-primed, isolated conjunctival mast cells. Stimulation of the co-stimulatory axis of CCR2 by MCP-1 is essentially required for mast cell-mediated hypersensitivity reactions in mouse eyes.

Reconstitution of Connective Tissue Type Conjunctival Mast Cells in KitW-sh/W-sh Mice by Adoptive Transfer of Bone Marrow-Derived Cultured Mast Cells

Reconstitution of Connective Tissue Type Conjunctival Mast Cells in KitW-sh/W-sh Mice by Adoptive Transfer of Bone Marrow-Derived Cultured Mast Cells

Ocular anti‐allergic compounds selectively inhibit human mast cell cytokines in vitro and conjunctival cell infiltration in vivo

Conjunctival mast cells (MCs) are important effector cells in seasonal allergic conjunctivitis, via histamine and cytokine secretion. Several new anti-allergic eye drops stabilize MCs and block histamine receptors, but their anti-inflammatory effects are unclear. Anti-allergic drugs were compared for their anti-inflammatory effects in an in vitro model of human MC activation and in an experimental murine model of allergic conjunctivitis. Human cord blood stem cell-derived (CBMC) and conjunctival biopsy-derived MCs were stimulated via FcepsilonRI, degranulation and histamine release were assayed at 1 h and cytokine secretion at 24 h using multiplex arrays. Mice sensitized to short ragweed pollen were given anti-allergics topically before allergen challenge, and conjunctival immuno-staining was performed at 24 h. After a 1 h stimulation, 80% of the CBMC had degranulated and secreted histamine (27.9+/-4.7 ng/10(6) cells; P<0.05). Pre-treatment by all drugs significantly reduced histamine and TNF-alpha, whereas IL-5, IL-8, IL-10 and TNF-beta profiles were differentially decreased. For conjunctival biopsy-derived cultures (n=11), FcepsilonR1 stimulation increased histamine, TNF-alpha, TNF-beta, IL-5 and IL-8 levels and the production of IL-5, IL-6 (P<0.05), histamine and IL-8 (P<0.01) was inhibited by epinastine. In vivo, epinastine and olopatadine pre-treatment significantly reduced the clinical scores and eosinophil numbers (n=6; P<0.05) while epinastine also reduced neutrophils (P<0.02). Differential effects on MC cytokine inhibition were observed, with epinastine inhibiting MC secretion of IL-5, IL-8, IL-10 and conjunctival neutrophil infiltration. The anti-allergic drugs have anti-histamine and mast-cell stabilizing properties but might differ in clinical improvement depending on the individual and the cytokines involved.

IL-10 confers protection from mast cell degranulation in a mouse model of allergic conjunctivitis

IL-10 is a regulatory cytokine known to inhibit allergic and inflammatory events. Mast cells (MC) are effector cells which when stimulated release histamine, chemokines and cytokines that initiate the allergic inflammatory response. Recent studies have shown that IL-10 regulates MC function by affecting cytokine production and expression of FcɛR1 in in vitro assays. Using IL-10 knockout (IL10KO) mice, we examined the effect of its absence on MC susceptibility to degranulation by the basic secretagogue, Compound 48/80 (C48/80). C48/80 is a receptor mimetic that directly activates G proteins and stimulates vigorous MC degranulation. For these studies we stimulated conjunctival MC with C48/80 and found that conjunctival MC of IL10KO mice exhibit increased degranulation compared with wild type mice. Reconstitution of IL10KO mice by adding rIL-10 24 h prior to challenge with C48/80 conferred increased resistance of MC to the degranulatory effects of C48/80. The protective effect therefore appears to be due to the presence of IL-10. This is the first in vivo rodent study which reports a novel role of IL-10 in stabilizing mast cells from degranulation by a secretagogue, by as of yet an unknown mechanism.

Primary conjunctival mast cell tumor in a Labrador Retriever

A 4-year-old, intact male Labrador Retriever with a rapidly progressive conjunctival mass was evaluated. Ocular examination showed a 2-cm elongated mass arising from the superior bulbar conjunctiva of the left eye. The mass resulted in distortion of the palpebral fissure and contacted the superior aspect of the cornea without modifying its structure; no adhesion to the sclera was detected. The superior palpebral conjunctiva was unaffected, and the remaining ocular examination was normal. The initial diagnostic work-up included CBC, serum biochemical analysis, urinalysis, and fine needle biopsy of the mass. A poorly differentiated mast cell tumor was diagnosed by cytology. Immunocytochemistry was performed to evaluate Ki-67 proliferation index, and 54/1000 tumoral nuclei showed a dark red staining. After a complete clinical staging, the mass was excised and identified histologically as a grade-II mast cell tumor. An adjuvant treatment with prednisone and vinblastine was instituted because of the limited excisional margins. No evidence of local recurrence or metastasis has been apparent during the 29-month follow-up period. This report contributes to the current literature pertaining to canine conjunctival mast cell tumors; unfortunately, the paucity of case reports and the absence of large studies regarding this tumor make conclusions regarding its biologic behavior impossible.