Jaafar El Annan

University of Louisville, Louisville, KY, United States

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Publications (10)38.2 Total impact

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    ABSTRACT: PURPOSE:: We have previously reported that mouse kallikrein (KLK) 22 in the lacrimal and salivary glands is an autoantigen that can induce primary Sjogren syndrome (SS) in rats. In this study, we determine whether the production of antibodies against tissue KLK is specific for SS and whether the antibody can be used as a biomarker for the diagnosis in humans. METHODS:: Sera from 11 patients diagnosed with SS, 8 patients with dry eye disease (DED), and 8 normal age/sex-matched controls (NL) were collected for detecting antibodies against tissue KLK1, KLK11, KLK12, and KLK13 by capture enzyme-linked immunosorbent assay. RESULTS:: Anti-KLK11 antibody was significantly higher in the SS than in the DED (P = 0.05) and NL (P < 0.01) groups, with no difference in the level of this antibody between the DED and NL groups. In addition, receiver operating characteristic analysis revealed that, at or above an optical density cutoff point of 0.2695, anti-KLK11 antibody has a sensitivity of 82% and a specificity of 94% to distinguish the SS group from the other groups. CONCLUSIONS:: Our results suggest that anti-KLK11 might be a novel biomarker for SS in humans. Further investigation is required to confirm this finding and to establish the exact role of KLK11 in the pathogenesis of SS.
    Cornea 10/2012; · 1.75 Impact Factor
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    ABSTRACT: Programmed death ligand-1 (PD-L1) plays a critical role in T-cell regulatory function. Here, we report a newly discovered effect of PD-L1 on angiogenesis. We demonstrate that PD-L1 and its receptor CD80, but not PD-1, are expressed by primary murine lung and heart vascular endothelial cells and the miscrovascular endothelial cell line (MS1) at both the mRNA and protein levels in vitro. The inhibition of PD-L1 or CD80 expression in MS1 cells, by small-interfering RNA transfection, led to a significant up-regulation of vascular endothelial growth factor receptor 2 expression and cell proliferation levels in MS1 cells. Furthermore, MS1 cells were found to have a significantly lower proliferation and vascular endothelial growth factor receptor 2 expression levels when they were co-cultured with PD-L1-expressing normal corneal epithelial cells, as compared to MS1 cells co-cultured with PD-L1(-/-) corneal epithelial cells. In a suture-induced corneal angiogenesis model, we observed a significantly higher level of angiogenic response in PD-L1(-/-) knockout mice as compared to wild-type mice, although there was no significant difference in the expression of inflammatory cytokines (interleukin-1α, interleukin-1β, or tumor necrosis factor-α) or the infiltration of innate immune cells (neutrophils and macrophages) between the two groups. We conclude that the expression of PD-L1 in both vascular endothelial cells and corneal epithelial cells regulates corneal angiogenesis.
    American Journal Of Pathology 04/2011; 178(4):1922-9. · 4.60 Impact Factor
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    ABSTRACT: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b(+)/LYVE-1(+) monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II(hi)) antigen-presenting cells to the lymphoid compartment. Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P < .001) and lymphatic caliber (P < .02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b(+)/LYVE-1(+) monocytic cells to the cornea and homing of mature CD11b(+) antigen-presenting cells to the draining lymph nodes were also associated with DED. Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.
    Archives of ophthalmology 07/2010; 128(7):819-24. · 3.86 Impact Factor
  • Janet S Sunness, Jaafar El Annan
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    ABSTRACT: Refraction often may be overlooked in low-vision patients, because the main cause of vision decrease is not refractive, but rather is the result of underlying ocular disease. This retrospective study was carried out to determine how frequently and to what extent visual acuity is improved by refraction in a low-vision population. Cross-sectional study. Seven hundred thirty-nine low-vision patients seen for the first time. A database with all new low-vision patients seen from November 2005 through June 2008 recorded presenting visual acuity using an Early Treatment Diabetic Retinopathy Study chart; it also recorded the best-corrected visual acuity (BCVA) if it was 2 lines or more better than the presenting visual acuity. Retinoscopy was carried out on all patients, followed by manifest refraction. Improvement in visual acuity. Median presenting acuity was 20/80(-2) (interquartile range, 20/50-20/200). There was an improvement of 2 lines or more of visual acuity in 81 patients (11% of all patients), with 22 patients (3% of all patients) improving by 4 lines or more. There was no significant difference in age or in presenting visual acuity between the group that did not improve by refraction and the group that did improve. When stratified by diagnosis, the only 2 diagnoses with a significantly higher rate of improvement than the age-related macular degeneration group were myopic degeneration and progressive myopia (odds ratio, 4.8; 95% confidence interval [CI], 3.0-6.7) and status post-retinal detachment (odds ratio, 7.1; 95% CI, 5.2-9.0). For 5 patients (6% of those with improvement), the eye that was 1 line or more worse than the fellow eye at presentation became the eye that was 1 line or more better than the fellow eye after refraction. A significant improvement in visual acuity was attained by refraction in 11% of the new low-vision patients. Improvement was seen across diagnoses and the range of presenting visual acuity. The worse-seeing eye at presentation may become the better-seeing eye after refraction, so that the eye behind a balance lens should be refracted as well. Proprietary or commercial disclosure may be found after the references.
    Ophthalmology 03/2010; 117(7):1442-6. · 5.56 Impact Factor
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    Jean Yared, Jaafar El Annan
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    ABSTRACT: Clear rhinorrhoea is a common symptom in patients with obstructive sleep apnoea (OSA), which may worsen with nasal continuous positive airway pressure treatment (nCPAP). However, rhinorrhoea can also be the presenting symptom of cerebrospinal fluid (CSF) leak, which is due to a communication between the subarachnoid space and the nasal cavity or sinuses. We report another case of a patient with OSA in whom CSF leak developed following the initiation of nCPAP treatment.
    Case Reports 01/2010; 2010.
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    ABSTRACT: PURPOSE. Given that dry eye disease (DED) is associated with T cell-mediated inflammation of the ocular surface and that PD-L1 is an important negative or inhibitory regulator of immune responses constitutively expressed at high levels by corneal epithelial cells, the authors studied the expression and function of PD-L1 in DED. METHODS. Dry eye was induced in untreated wild-type mice, PD-L1(-/-) mice, and wild-type mice treated with anti-PD-L1 antibody by exposing these mice to a desiccating environment in the controlled environment chamber modified with subcutaneous administration of scopolamine. Real-time PCR was used to quantify the expression of chemokine gene transcript levels of multiple CC and CXC chemokine ligands and receptors. Epifluorescence microscopy was used to evaluate corneal infiltration of CD3(+) T cells after immunohistochemical staining. RESULTS. The increased expression of specific chemokine ligands and receptors in PD-L1(-/-) corneas of normal mice is associated with significant increases in T-cell homing into these corneas. Similar, and more enhanced, increases in T-cell infiltration were observed in PD-L1(-/-) DED mice or DED mice treated with anti-PD-L1 antibody compared with controls. In addition, the authors found significantly decreased expression of PD-L1 by corneal epithelial cells in DED and significantly increased corneal fluorescein staining score with PD-L1 functional blockade using anti-PD-L1 antibody. CONCLUSIONS. Downregulation of corneal epithelial PD-L1 amplifies dry eye-associated corneal inflammation and epitheliopathy by increasing the expression of chemokine ligands and receptors that promote T-cell homing to the ocular surface.
    Investigative ophthalmology & visual science 12/2009; 51(7):3418-23. · 3.43 Impact Factor
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    ABSTRACT: Dry eye disease (DED) is associated with ocular surface inflammation that is thought to be mediated primarily by CD4 T cells. The purpose of this study was to investigate whether this T cell-mediated immune response is generated in the lymphoid compartment and to characterize the functional phenotype of the T cells activated in DED. DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled environment chamber and to systemic scopolamine. T cells from regional draining lymph nodes (LNs) of DED mice and normally sighted mice were analyzed for surface activation markers (CD69 and CD154), chemokine and cytokine receptors, and proliferation potential. Draining LNs of DED mice showed increased frequencies of CD69- and CD154-expressing T cells with higher proliferative capacity. In addition, these LN T cells primarily showed a helper T-cell (Th)1 phenotype, expressing significantly higher levels of IFN-gamma and IL-12Rbeta2 but not IL-4R. Similarly, the LNs of DED mice showed significantly increased frequencies of T cells expressing CXCR3 and CCR5, but not CCR4, suggesting a bias toward a Th1 phenotype. These data demonstrate that a Th1-type immune response is induced in the regional LNs of DED mice. The identification of specific cytokine/chemokine receptors overexpressed by these T cells may signify potential novel targets/strategies for the treatment of DED.
    Investigative ophthalmology & visual science 05/2009; 50(8):3802-7. · 3.43 Impact Factor
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    ABSTRACT: Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium-which shares the same alloantigens-is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such 'chimeric' allografts consisted of a C3H/He (H-2(k)) corneal epithelium over a C57BL/6 (H-2(b)) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2(d)) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4(+) interferon [IFN]-gamma(+)) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds.
    American Journal of Transplantation 04/2009; 9(3):473-82. · 6.19 Impact Factor
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    ABSTRACT: Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an incomplete understanding of its specific cellular and molecular pathogenic elements. Using a validated mouse model of DED, herein we functionally characterize the different T cell subsets, including regulatory T cells (Tregs) and pathogenic effector T cells, and determine their contribution to the pathogenesis of DED. Our data demonstrate the presence of dysfunctional Tregs and the resistance of pathogenic T cells, particularly Th17 cells, to Treg suppression in DED. In addition, we clearly show that in vivo blockade of IL-17 significantly reduces the severity and progression of disease, which is paralleled by a reduction in the expansion of Th17 cells and restoration of Treg function. Our findings elucidate involvement of a previously unknown pathogenic T cell subset (Th17) in DED that is associated specifically with Treg dysfunction and disease pathogenesis and suggest a new target for dry eye therapy.
    The Journal of Immunology 02/2009; 182(3):1247-52. · 5.52 Impact Factor
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    ABSTRACT: To study the effect of topical application of very late antigen 4 (VLA-4) small-molecule antagonist (anti-VLA-4 sm) in a mouse model of dry eye disease. Anti-VLA-4 sm (or control vehicle) was applied topically to mice placed in a controlled-environment chamber. Corneal fluorescein staining and conjunctival T-cell enumeration were performed in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva. Dry eye syndrome induced increased corneal fluorescein staining, corneal and conjunctival tumor necrosis factor alpha messenger RNA expression, and T-cell infiltration into the conjunctiva. Very late antigen 4 blockade significantly decreased corneal fluorescein staining compared with the untreated dry eye disease and control vehicle-treated groups (P < .001 and P = .02, respectively). In addition, VLA-4 blockade was associated with a significant decrease in conjunctival T-cell numbers (P < .001 vs control vehicle-treated group) and tumor necrosis factor-alpha transcript levels in the cornea (P = .04 vs control vehicle-treated group) and conjunctiva (P = .048 vs control vehicle-treated group). Application of topical anti-VLA-4 sm led to a significant decrease in dry eye signs and suppression of inflammatory changes at the cellular and molecular levels. Topical blockade of VLA-4 may be a novel therapeutic approach to treat the clinical signs and inflammatory changes accompanying dry eye disease.
    Archives of ophthalmology 01/2009; 126(12):1695-9. · 3.86 Impact Factor

Publication Stats

157 Citations
38.20 Total Impact Points

Institutions

  • 2010–2012
    • University of Louisville
      • Department of Ophthalmology and Visual Sciences
      Louisville, KY, United States
    • Schepens Eye Research Institute
      Boston, Massachusetts, United States
    • Greater Baltimore Medical Center
      Baltimore, Maryland, United States
  • 2009–2011
    • Massachusetts Eye and Ear Infirmary
      • • Department of Ophthalmology
      • • Schepens Eye Research Institute
      Boston, MA, United States
    • Harvard Medical School
      Boston, Massachusetts, United States