Omar M Durrani

Publications (8)29.33 Total impact

• Article: The role of 11beta-hydroxysteroid dehydrogenase 1 in adipogenesis in thyroid-associated ophthalmopathy.

  Jeremy W Tomlinson, Omar M Durrani, Iwona J Bujalska, Laura L Gathercole, Paul J Tomlins, Tristan T Q Reuser, Geoffrey E Rose, S John Curnow, Paul M Stewart, Elizabeth A Walker, Saaeha Rauz
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  ABSTRACT: Thyroid-associated ophthalmopathy (TAO) is a sight-threatening autoimmune disease in which de novo adipogenesis has been identified as a fundamental pathogenic mechanism. 11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) increases cortisol bioavailability and is pivotal in mediating glucocorticoid responses in adipose tissue and inflammation. In this study we characterize 11beta-HSD1 as a determinant of the adipogenic and inflammatory pathways in TAO orbital fat (OF) compared with normal OF. OF was harvested from 46 TAO and 44 control patients undergoing orbital surgery. Samples were examined by a combination of immunohistochemistry, real-time RT-PCR, primary cell culture, specific enzyme assays, colorimetric proliferation assays, and bead-based ELISA. Glucocorticoid (glucocorticoid receptor-alpha,11beta-HSD1, hexose-6-phosphate dehydrogenase) and inflammatory cytokines (IL-1beta, IL-1 receptor, IL-6, TNF-alpha, TNF-alpha inductible protein, TGF-beta2) target genes together with markers of late adipocyte differentiation (fatty-acid-binding-protein-4, glycerol-6-phosphate-dehydrogenase) were highly expressed in TAO whole OF (P < 0.05) compared with controls. Primary cultures of TAO OF stromal cells demonstrated greater 11beta-HSD1 oxoreductase activity (P < 0.05), which was regulated by cytokines, most notably TNF-alpha (P < 0.01), compared with controls. Activity increased across differentiation, and this was most marked in TAO cells (P < 0.01). Similarly, stromal cell proliferation was limited by incubation with cortisol in TAO cells only. Furthermore, cortisone decreased IL-6 (P < 0.005), IL-8 (P < 0.05), and macrophage chemoattractant protein-1 (P < 0.05) production by cultured TAO cells only, an effect that was abrogated by inhibition of 11beta-HSD1. Induction of 11beta-HSD1 activity and expression by inflammatory cytokines (TNF-alpha, IL-6) may enhance orbital adipocyte differentiation (adipogenesis) and limit proliferation in TAO. 11beta-HSD1 may also have a role in regulating the local orbital inflammatory response.
  The Journal of clinical endocrinology and metabolism 10/2009; 95(1):398-406. · 6.50 Impact Factor
• Article: Bicanalicular obstruction in lichen planus: a characteristic pattern of disease.

  Omar M Durrani, David H Verity, George Meligonis, Geoffrey E Rose
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  ABSTRACT: Lichen planus, an idiopathic mucocutaneous inflammatory disease, has only once been reported to cause lacrimal drainage obstruction. The authors present a series of patients with epiphora resulting from systemic lichen planus and describe the characteristic pattern of lacrimal canalicular blockage. Retrospective noninterventional case series. Eight patients (5 women, 3 men) with a median presenting age of 49 years (range, 39-60 years). A retrospective review of case notes for patients attending the lacrimal clinic between 1998 and 2005 was performed to identify patients with nontraumatic lacrimal canalicular obstruction. In addition to demographic information, the data collected included a history of periocular herpetic infection, administration of systemic 5-fluorouracil, other causes of canalicular obstruction, the extent of proximal and distal canalicular obstruction (noted during surgery), the type of surgery, and the surgical outcomes. Identification of patients with biopsy-proven systemic lichen planus who had conjunctival and canalicular disease and documentation of the extent and severity of canalicular obstruction. Of the 184 patients with canalicular obstruction identified during the study period, 8 had lichen planus. Bilateral, bicanalicular involvement was present in 7 of 8 lichen planus patients, with 3 of 8 patients having completely obstructed canaliculi. Primary dacryocystorhinostomy (DCR) with retrograde canaliculostomy was performed in 4 of 8 patients, but all required secondary placement of Lester Jones canalicular bypass tubes. The other 4 patients had either primary DCR alone (both eyes in 1 patient, with solely canalicular stenosis) or DCR with primary placement of Jones tubes (6 eyes in 3 patients). Histologic examination of pericanalicular tissues in 2 patients showed features consistent with lichen planus. Lacrimal involvement in lichen planus is characterized by severe bilateral bicanalicular occlusion involving most of the length of affected canaliculi, and placement of a Jones canalicular bypass tube is generally required to control symptoms.
  Ophthalmology 03/2008; 115(2):386-9. · 5.45 Impact Factor
• Source

  Available from: Iwona Bujalska

  Article: Characterisation of 11beta-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat.

  Iwona J Bujalska, Omar M Durrani, Joseph Abbott, Claire U Onyimba, Pamela Khosla, Areeb H Moosavi, Tristan T Q Reuser, Paul M Stewart, Jeremy W Tomlinson, Elizabeth A Walker, Saaeha Rauz
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  ABSTRACT: Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0 x 001). Although immunohistochemical analyses demonstrated resident CD68+ cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha compared with SC and OM. OF harbours a large CD68+ population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease.
  Journal of Endocrinology 02/2007; 192(2):279-88. · 3.55 Impact Factor
• Article: Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis.

  S John Curnow, Francesco Falciani, Omar M Durrani, C M Gemmy Cheung, Emma J Ross, Kaska Wloka, Saaeha Rauz, Graham R Wallace, Mike Salmon, Philip I Murray
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  ABSTRACT: To extensively characterize the complex network of cytokines present in uveitis aqueous humor (AqH), and the relationships between cytokines and the cellular infiltrate. AqH from noninflammatory control subjects and patients with idiopathic, Fuchs' heterochromic cyclitis (FHC), and herpes-viral or Behçet's uveitis were analyzed for IL-1beta, -2, -4, -5, -7, -8, -10, -12, -13, -15, TNFalpha, IFNgamma, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (Eotaxin), TGFbeta2, and CXCL12 (SDF-1), using multiplex bead immunoassays. The cellular infiltrate was also determined for each sample. Idiopathic uveitis AqH, compared with noninflammatory controls, was characterized by high levels of IL-6, IL-8, CCL2 and IFNgamma, the levels of which correlated with each other. For IL-6 and IL-8 these levels were proportional to the number of neutrophils present. By contrast, the levels of both TGFbeta2 and CXCL12 decreased in idiopathic uveitis AqH with increasing inflammation. Cluster analysis showed a degree of segregation between noninflammatory and idiopathic uveitis AqH. Further examination using random forest analysis yielded a complete distinction between these two groups. The minimum cytokines required for this classification were IL-6, IL-8, CCL2, IL-13, TNFalpha, and IL-2. Application of multiplex bead immunoassays has allowed us to identify distinct patterns of cytokines that relate to both clinical disease and the cellular infiltrates present. Bioinformatics analysis allowed identification of cytokines that differentiate idiopathic uveitis from noninflammatory control AqH and are likely to be important for the pathogenesis of uveitis.
  Investigative Ophthalmology &amp Visual Science 12/2005; 46(11):4251-9. · 3.60 Impact Factor
• Source

  Available from: Stefan Rose-John

  Article: Inhibition of T cell apoptosis in the aqueous humor of patients with uveitis by IL-6/soluble IL-6 receptor trans-signaling.

  S John Curnow, Dagmar Scheel-Toellner, Will Jenkinson, Karim Raza, Omar M Durrani, Jeff M Faint, Saaeha Rauz, Kaska Wloka, Darrell Pilling, Stefan Rose-John, Christopher D Buckley, Philip I Murray, Mike Salmon
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  ABSTRACT: A fundamental mechanism of immune privilege in the eye is the induction of T lymphocyte apoptosis. Intraocular inflammation in uveitis implies compromise of immune privilege. This study sought to determine whether apoptosis of T cells is actively inhibited in patients with uveitis and by what pathways this may occur. Apoptotic lymphocytes were found to be absent from aqueous humor (AqH) of virtually all patients with recent-onset uveitis. However, T cells removed from the eye were highly susceptible to both spontaneous and Fas ligand-induced apoptosis in vitro. AqH from patients with uveitis had no modulatory effect on Fas ligand-induced apoptosis, but strongly suppressed survival factor deprivation-induced apoptosis. In contrast, noninflammatory AqH from patients undergoing cataract surgery had no modulatory effects on apoptosis at all. These data suggest that triggering of the Fas pathway is diminished in uveitis, and also that homeostatic resolution through survival factor deprivation-induced apoptosis is inhibited by factors present in AqH. The most widely recognized pathways, common gamma-chain cytokines and type I IFNs, did not contribute to AqH-mediated T cell survival. High levels of both IL-6 and soluble IL-6R were found in AqH. IL-6 alone did not induce T cell survival, because IL-6R expression on T cells in AqH was too low to facilitate signaling. However, combinations of IL-6 and soluble IL-6R were highly effective inhibitors of T cell apoptosis, suggesting that the trans-signaling pathway is likely to be a key mediator of T cell apoptosis inhibition mediated by uveitis AqH.
  The Journal of Immunology 11/2004; 173(8):5290-7. · 5.79 Impact Factor
• Source

  Available from: ncbi.nlm.nih.gov

  Article: The danger of wearing an anorak.

  Chui M G Cheung, Omar M Durrani, Ming S Lim, Mahesh Ramchandani, Somnath Banerjee, Philip I Murray
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  ABSTRACT: Campaigns to reduce road traffic accidents have paid little attention to the way headgear could interfere with vision. Binocular visual field measurement was undertaken in six healthy volunteers wearing four different types of anorak. All four anoraks greatly reduced the horizontal and superior field of vision. The anorak producing the worst reduction resulted in a width of vision of 99 degrees and only 15 degrees of vision above eye level, versus 167 degrees and 52 degrees respectively without an anorak. Anorak wearers should turn their heads to look sideways before crossing the road.
  Journal of the Royal Society of Medicine 05/2002; 95(4):192-3. · 1.41 Impact Factor
• Article: Use of a novel topical hemostatic sealant in lacrimal surgery: a prospective, comparative study.

  Omar M Durrani, Arosha I Fernando, Tristan Q Reuser
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  ABSTRACT: FloSeal Matrix is a new, two-component (collagen granules and thrombin), topical hemostatic sealant. We prospectively evaluated the role of FloSeal Matrix in achieving hemostasis in dacryocystorhinostomy (DCR) surgery and its intraoperative characteristics (ease of use). We hypothesize that FloSeal will efficiently control bleeding in patients and eliminate the need for postoperative intranasal dressing. FloSeal was used during surgery in 10 consecutive patients undergoing DCR. A further 10 consecutive patients (comparative group) had DCR without FloSeal; nasal packing was performed to control postoperative bleeding. The severity of postoperative bleeding and patient comfort were compared between the two groups at three time points (immediately after surgery, 12 hours after surgery, and 24 hours after surgery). All patients in the comparative group had some degree of postoperative bleeding (minimal to severe), whereas the nine patients in the FloSeal group had none or minimal bleeding. The difference was statistically significant at all three measured time points (p = 0.047, 0.006, 0.05). The FloSeal group also had less postoperative discomfort (p = 0.0001). FloSeal Matrix is an effective hemostasis adjunct in patients undergoing lacrimal surgery. It has the added benefits of high patient satisfaction and ease of use.
  Ophthalmic Plastic and Reconstructive Surgery 23(1):25-7. · 0.69 Impact Factor
• Article: Primary anti-phospholipid antibody syndrome (APS): current concepts.

  Omar M Durrani, Caroline Gordon, Philip I Murray
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  ABSTRACT: Primary anti-phospholipid syndrome (APS) is a thrombophilic state characterized by recurrent arterial and venous thrombosis, recurrent pregnancy loss, and the presence of circulating anti-phospholipid antibodies that may be responsible for thrombophilia and pregnancy morbidity. Ophthalmologic features are present in 15-88% of the patients with primary APS, thus ophthalmologists are one of the first physicians to whom the patient will present. An accurate diagnosis may save the patient from recurrent, potentially life-threatening thrombosis. In the U.S.A., an estimated 35,000 new cases of APS-related venous thrombosis occur each year in a population that is several decades younger than the patient population typically affected by thrombosis. Clinical features, such as chorea, transverse myelitis, cardiac valvular lesions, and accelerated atherosclerosis, are hypothesized to be due to a direct tissue-antibody interaction and cannot be explained purely by thrombosis. The use of recently proposed, well-defined diagnostic criteria, and better standardization of laboratory assays for the anti-phospholipid antibodies should help enable epidemiological surveys to establish the prevalence of these antibodies in patients with thrombosis and in the general population. Diagnosis of APS should be considered in all patients with recurrent systemic or ocular thrombosis in the absence of known risk factors. Several well-designed prospective studies show an increased risk of thrombosis in the presence of medium to high antibody level. With ocular involvement in as many as 88% of APS patients, an ophthalmic assessment should be an integral part of the clinical work-up of any patient with suspected or confirmed APS. The presence of isolated ocular thrombophilia with persistently elevated anti-phospholipid antibodies or lupus coagulant should confirm the diagnosis of APS. Management of these patients must be a multi-disciplinary effort with either a rheumatologist or a hematologist having the overall responsibility for coordinating treatment and monitoring the patient's immune status and anticoagulation. Treatment of isolated ocular thrombophilia in the presence of moderate to high titers of antiphospholipid antibodies should be on the same principles as patients with APS to prevent recurrent ocular or cerebral thrombosis.
  Survey of Ophthalmology 47(3):215-38. · 2.35 Impact Factor