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Houston, TX, United States

Haque R.M.,Inspire Pharmaceuticals | Torkildsen G.L.,ORA Inc | Brubaker K.,Inspire Pharmaceuticals | Zink R.C.,Inspire Pharmaceuticals | And 3 more authors.
Cornea | Year: 2010

Purpose: To evaluate the effect of 4 weeks of treatment with azithromycin ophthalmic solution 1% on eyelid bacterial load, tear cytokines, and signs and symptoms of blepharitis. Methods: Twenty-six subjects (mean age 64.2 years; 65% female; 100% white) with moderate to severe blepharitis received azithromycin ophthalmic solution 1% in the absence of warm compresses or eyelid scrubs for 28 days (twice a day on days 1 and 2 and once a day on days 3-28). Blepharitis signs and symptoms were evaluated at baseline (day 1) and compared with end of treatment (day 29) and 2 follow-up visits (2 and 4 weeks posttreatment). Tear collection and eyelid margin bacterial cultures were performed at baseline and end of treatment. Tear cytokines were measured by a multiplex immunobead assay. Results: Four-week azithromycin treatment demonstrated significant decreases from baseline in investigator-rated signs of meibomian gland plugging, eyelid margin redness, palpebral conjunctival redness, and ocular discharge (P ≤ 0.002) at day 29, which persisted 4 weeks posttreatment (P ≤ 0.006). Subject-reported symptoms of eyelid itching, foreign body sensation/sandiness/ grittiness, ocular dryness, ocular burning/pain, and swollen/heavy eyelids also demonstrated significant improvement from baseline (P < 0.001 for all symptoms and time points, except P = 0.037 for ocular dryness at visit 4). Eyelid margin culture exhibited significant decreases in coagulase-negative staphylococci and Corynebacterium xerosis bacteria. Changes in tear cytokine concentrations were not observed. Twelve subjects experienced 19 adverse events, 15 of which were ocular and none of which were serious. Conclusion: Azithromycin provided significant improvement in signs and symptoms of blepharitis after 4 weeks of treatment compared with baseline and persisted in the 4-week follow-up period. © 2010 by Lippincott Williams and Wilkins. Source

Pflugfelder S.C.,Cullen Eye Institute | Stern M.E.,Cullen Eye Institute | Stern M.E.,DuPont Company
Expert Review of Clinical Immunology | Year: 2014

The 4th Cullen Symposium, held April 17 and 18, 2014, included expert researchers in mucosal immunity of the eye and other mucosal surfaces, particularly the gut. The theme of the meeting was environmental sensing mechanisms in mucosal tissues and their relevance for initiating ocular surface inflammation in dry eye. There are a number of shared features between the ocular surface and other mucosal surfaces, but distinct differences may exist in the type and distribution of mucins and microbiota. Mechanisms to regulate DC maturation and prevent tissue-damaging inflammation are shared among these sites. Epithelial and dendritic cells are key environmental sensors participating in initiation of innate and adaptive immune responses in response to a variety of environmental stresses. © 2014 Informa UK Ltd. Source

McClellan A.J.,Cullen Eye Institute | Volpe E.A.,Cullen Eye Institute | Zhang X.,Cullen Eye Institute | Darlington G.J.,Baylor College of Medicine | And 3 more authors.
American Journal of Pathology | Year: 2014

Dry eye in humans displays increased prevalence in the aged and in women. Here, we investigated the ocular surfaces and lacrimal glands of aged mice of both sexes. We surveyed three different ages [young, middle-aged (6 to 9 months), and elderly] by investigating severity markers of dry eye disease (DED). We observed an age-dependent dry eye phenotype as early as 6 to 9 months: increased corneal surface irregularity, increased corneal barrier disruption, conjunctival CD4+ T-cell infiltration, and loss of mucin-filled goblet cells. Expression of interferon-γ, IL-17 mRNA transcripts was increased in the conjunctiva and IL-17A, matrix metallopeptidase 9, and chemokine ligand 20 in the corneas of elderly mice. Elderly male mice develop more of a skewed response of type 1 T helper cell, whereas female mice have a bias toward type 17 T helper cell in the conjunctiva. In the lacrimal gland, an increase in CD4+ and CD8+ T cells and B cells and a decrease in activated dendritic cells were observed. Adoptive transfer of CD4+ T cells isolated from elderly mice transferred DED into young immunodeficient recipients, which was more pronounced from male donors. Our findings show the development of DED in aging mice. Pathogenic CD4+ T cells that develop with aging are capable of transferring DED from older mice to naive immunodeficient recipients. Taken together, our results indicate that age-related autoimmunity contributes to development of DED with aging. Copyright © 2014 American Society for Investigative Pathology. Source

De Paiva C.S.,Cullen Eye Institute | Raince J.K.,Cullen Eye Institute | McClellan A.J.,Cullen Eye Institute | Shanmugam K.P.,Cullen Eye Institute | And 7 more authors.
Mucosal Immunology | Year: 2011

Although the effects of the interleukin 13 (IL-13) on goblet cell (GC) hyperplasia have been studied in the gut and respiratory tracts, its effect on regulating conjunctival GC has not been explored. The purpose of this study was to determine the major IL-13-producing cell type and the role of IL-13 in GC homeostasis in normal murine conjunctiva. Using isolating techniques, we identified natural killer (NK)/natural killer T (NKT) cells as the main producers of IL-13. We also observed that IL-13 knockout (KO) and signal transducer and activator of transcription 6 knockout (STAT6KO) mice had a lower number of periodic acid Schiff (PAS)GCs. We observed that desiccating stress (DS) decreases NK population, GCs, and IL-13, whereas it increases interferon-γ (IFN-γ) mRNA in conjunctiva. Cyclosporine A treatment during DS maintained the number of NK/NKT cells in the conjunctiva, increased IL-13 mRNA in NK cells, and decreased IFN-γ and IL-17A mRNA transcripts in NK and NK populations. C57BL/6 mice chronically depleted of NK/NKT cells, as well as NKT cell-deficient RAG1KO and CD1dKO mice, had fewer filled GCs than their wild-type counterparts. NK depletion in CD1dKO mice had no further effect on the number of PAS cells. Taken together, these findings indicate that NKT cells are major sources of IL-13 in the conjunctival mucosa that regulates GC homeostasis. © 2011 Society for Mucosal Immunology. Source

Henriksson J.T.,University of Houston | De Paiva C.S.,Cullen Eye Institute | Farley W.,Cullen Eye Institute | Pflugfelder S.C.,Cullen Eye Institute | And 2 more authors.
Cornea | Year: 2013

PURPOSE:: To investigate the normal palpebral conjunctival histology in C57BL/6 mice and the structural changes that occur in a dry eye model. METHODS:: Twenty-four male and female C57BL/6 mice, 8 untreated and 16 exposed to experimental ocular surface desiccating stress (DS). Ocular dryness was induced by administration of scopolamine hydrobromide (0.5 mg/0.2 mL) four times a day for 5 days (DS5) or 10 days (DS10). Counts and measurements were obtained using anatomical reference points, and goblet cell density was investigated with a variety of stains. RESULTS:: Near the junction between the lid margin and the normal palpebral conjunctiva, the epithelium had an average thickness of 45.6 ± 10.5 μm, 8.8 ± 2.0 cell layers, versus 37.7 ± 5.6 μm, 7.4 ± 1.3 layers in DS10 (P < 0.05). In the goblet cell-populated palpebral region, the normal epithelium was thicker (P < 0.05) than on DS5 and DS10. In the control, 43% of the goblet cells were covered by squamous epithelium compared with 58% (DS5) and 63% (DS10) (P < 0.05). A decreased number of periodic acid-Schiff (PAS)-stained goblet cells and Alcian blue-stained goblet cells were observed in the dry eye. Not all goblet cells were stained with PAS and Alcian blue. CONCLUSION:: The mouse palpebral conjunctival epithelium was structurally similar to the human. After DS, the palpebral conjunctival epithelium decreased in thickness and goblet cell access to the surface seemed to be inhibited by surrounding epithelial cells, potentially slowing down their migration to the surface. Differential staining with PAS and Alcian blue suggests that there may be different subtypes of conjunctival goblet cells. Copyright © 2012 by Lippincott Williams Wilkins. Source

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