A nerve-goblet cell association promotes allergic conjunctivitis through rapid antigen passage.

The penetration of allergens through the epithelial layer is the initial step in the development of allergic conjunctivitis. Although pollinosis patients manifest symptoms within minutes after pollen exposure, the mechanisms of the rapid transport of the allergens remain unclear. In the present study, we found that the instillation of pollen shells rapidly induces a large number of goblet cell-associated antigen passages (GAPs) in the conjunctiva. Antigen acquisition by stromal cells, including macrophages and CD11b+ dendritic cells, correlated with surface GAP formation. Furthermore, a substantial amount of antigen was transported to the stroma during the first 10 minutes of pollen exposure, which was sufficient for the full induction of an allergic conjunctivitis mouse model. This inducible, rapid GAP formation and antigen acquisition were suppressed by topical lidocaine or trigeminal nerve ablation, indicating that the sensory nervous system plays an essential role. Interestingly, pollen shell-stimulated GAP formation was not suppressed by topical atropine, suggesting that the conjunctival GAPs and intestinal GAPs are differentially regulated. These results identify pollen shell-induced GAP as a therapeutic target for allergic conjunctivitis.

The protective role of conjunctival goblet cell mucin sialylation.

Gel-forming mucins secreted by conjunctival goblet cells have been implicated in the clearance of allergens, pathogens, and debris. However, their roles remain incompletely understood. Here we show that human and mouse conjunctival goblet cell mucins have Alcian blue-detectable sialic acids, but not sulfates in the steady state. Interestingly, Balb/c mouse strain lacks this sialylation due to a point mutation in a sialyltransferase gene, St6galnac1, which is responsible for sialyl-Tn synthesis. Introduction of intact St6galnac1 to Balb/c restores the sialylation of conjunctival goblet cell mucus. Sialylated mucus efficiently captures and encapsulates the allergen particles in an impenetrable layer, leading to the protection of mice from the development of allergic conjunctivitis. Expression of ST6GALNAC1 and sialyl-Tn is upregulated in humans under conditions with chronic stimuli. These results indicate that the sialylated glycans on the ocular mucins play an essential role in maintaining the conjunctival mucosa by protecting from the incoming foreign bodies such as allergen particles.

Effects of intravitreal injection of ranibizumab and aflibercept for branch retinal vein occlusion on the choroid: a retrospective study.

BACKGROUND: Macular edema is found in more than half of branch retinal vein occlusion (BRVO) cases, leading to visual loss in most of these cases. Intravitreal injection of anti-vascular endothelial growth factor is currently the standard treatment for macular edema due to BRVO (BRVO-ME). The difference in the effects of aflibercept and ranibizumab on the choroid in BRVO-ME is unknown. Therefore, we analyzed the effects of intravitreal injection of ranibizumab and aflibercept on BRVO-ME. METHODS: We retrospectively observed changes in choroidal thickness in the subfoveal region in 36 patients with BRVO-ME who visited the Department of Ophthalmology at the Juntendo University Urayasu Hospital. The patients were treated with intravitreal injection of aflibercept or ranibizumab and followed up for 12 months or more. RESULTS: The observed point bifurcated into the affected and non-affected sides 500 µm from the fovea. The central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) were 564.2 ± 268.5 µm and 228.8 ± 50.1 µm, respectively, in the ranibizumab group (16 patients, 16 eyes) and 542.4 ± 172.5 µm and 246.1 ± 59.1 µm, respectively, in the aflibercept group (20 patients, 20 eyes). The changes in CMT at 12 months were 324.0 ± 262.6 µm and 326.55 ± 187.2 µm in the ranibizumab and aflibercept groups, respectively, with no significant difference (p = 0.97). Similarly, the changes in SFCT over 12 months were not significant between the groups (ranibizumab, 41.9 ± 33.0 µm; aflibercept, 43.8 ± 43.8 µm, p = 0.89). CONCLUSION: The effects of ranibizumab and aflibercept on choroidal thickness in BRVO-ME were the same regardless of the site. Although BRVO is a retinal disease, we hope that we can further explore the mechanism of BRVO-ME by observing changes in the choroid in the future.

Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice.

PURPOSE: We aimed to clarify the role of particulate allergen exposure to the conjunctiva in the development of allergic conjunctivitis. METHODS: We administered ragweed pollen suspension, pollen extract, pollen shell, particulate air pollutants, and their combinations to the mouse conjunctiva five days a week without prior sensitization. Clinical signs were scored. Histological changes, cellular infiltrations, mRNA expressions, lymph node cell recall responses, and serum immunoglobulin levels were assessed. Immune cell-depleting antibodies and ST2 knockout mice were used to investigate the cellular and molecular requirements. RESULTS: Pollen suspension, but not the extract or shell alone, induced robust eosinophilic conjunctivitis, accompanied by a proliferative response of epithelial cells. A combination of pollen extract and shell completely restored eosinophil accumulation. In addition, eosinophilic conjunctivitis was induced by a mixture of particulate air pollutants and pollen extract. Mechanistically, eosinophil accumulation was ameliorated by deficiency of the IL-33 receptor ST2 and abolished by depleting CD4+ T cells. Pollen shells, but not the extract, induced IL-33 release from conjunctival epithelial cells in vivo. CONCLUSIONS: Our results indicate the non-redundant roles for the allergens' particulate properties and soluble factors in the development of allergic conjunctivitis.

Seasonal variation in the occurrence of retinal vein occlusion: a 4-year cross-sectional study.

BACKGROUND: Retinal vein occlusion (RVO) is a common retinal vascular disease that causes a loss of vision. Therefore, we investigated whether there is seasonal variation in the onset of RVO, to examine the possibility of preventing it. METHODS: Patients with RVO who were treated at the Juntendo University Urayasu Hospital between April 2013 and March 2017 were included in this retrospective study. The season in which the RVO occurred was recorded for each case, and the cases were grouped into six 2-month periods based on the month of RVO, and classified by age, sex and hypertension status. The frequency of occurrence of RVO across seasons was compared using a chi-squared test. RESULTS: A total of 348 patients with RVO presented during the study period, with information regarding the date of RVO onset. The cohort of 348 consisted of 167 males and 181 females who, overall, had a mean age of 64.0 years (range 17-96 years). The highest incidence of RVO onset was during January/February, with the lowest incidence during July/August. Patient age, sex and hypertension status did not influence the results. CONCLUSIONS: The seasonal onset of RVO tended to be higher in January/February and May/June, and lower in July/August. These findings suggest that eyecare professionals should be more vigilant in watching for the occurrence of RVO during winter and the rainy season, regardless of the patient's sex, age or hypertension status.

Occurrence of Carcinoma of the Pancreas Following Nilotinib Therapy for Chronic Myeloid Leukemia: Report of a Case with Review of the Literature.

The patient, a 79-year-old Japanese man, was diagnosed with the chronic phase of chronic myeloid leukemia and begun on nilotinib therapy in April 2011. The therapeutic response was major molecular response in August. About 19 months after the start of nilotinib therapy at 400 mg/day (November 2012), an adenocarcinoma (24 x 20 mm) confined to the head of the pancreas developed. In February 2013, a pancreaticoduodenectomy was performed. The therapy regimen was switched to dasatinib at 100 mg/day, beginning in April. The response was still major molecular response with no recurrence of pancreatic carcinoma in July 2013. There have been 29 reported cases of secondary neoplasms associated with nilotinib therapy. These secondary neoplasms were characterized by relatively frequent occurrence of papilloma (6 cases), gastric cancer (3 cases), fibroma (3 cases), and thyroid neoplasms (2 cases). The present case, however, is the first to be reported as carcinoma of the pancreas. This report describes the case.