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Table of Contents - WOC 2012

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PO-IMM-13<br />

Identification <strong>of</strong> Autoantibodies against TRPM1 in Patients with<br />

Paraneoplastic Retinopathy Associated with ON Bipolar Cell<br />

Dysfunction<br />

Kondo Mineo (1) , Sanuki Rikako (2) , Ueno Shinji (1) , Terasaki Hiroko (1) , Furukawa<br />

Takahisa (2)<br />

1. Nagoya University Graduate School <strong>of</strong> Medicine<br />

2. Osaka Bioscience Institute<br />

Purpose: Paraneoplastic retinopathy (PR), including cancer-associated<br />

retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a<br />

progressive retinal disease caused by antibodies generated against neoplasms<br />

not associated with the eye. The purpose <strong>of</strong> the current study is to investigate<br />

whether there are autoantibodies against transient receptor potential cation<br />

channel, subfamily M, member 1 (TRPM1) in the sera <strong>of</strong> PR patients exhibiting<br />

ON bipolar cell dysfunction.<br />

Methods: We performed detailed electroretinographic (ERG) analyses and<br />

Western blot analysis in one lung CAR and 26 MAR patients, who were thought<br />

to have ON-bipolar cell dysfunction.<br />

Results: We identified autoantibodies against TRPM1 in the serum <strong>of</strong> a patient<br />

with lung CAR, and two <strong>of</strong> 26 MAR patients. The ERGs <strong>of</strong> these patients<br />

showed a severely reduced ON response with normal OFF response,<br />

indicating that the defect is in the signal transmission between photoreceptors<br />

and ON bipolar cells.<br />

Conclusion: Our study reveals TRPM1 to be one <strong>of</strong> the autoantigens targeted<br />

by autoantibodies in at least some patients with CAR or MAR associated with<br />

retinal ON bipolar cell dysfunction.<br />

PO-IMM-14<br />

Evaluation <strong>of</strong> systemic biomarkers in diabetic macular edema and<br />

proliferative diabetic retinopathy and relation to outcome after<br />

ranibizumab therapy<br />

Voegeler Jessica (1,2) , Pohl Karin (2) , Faerber Lothar (1,2) , Lang Gabriele E. (3) ,<br />

Straub Rainer H. (1)<br />

1. University <strong>of</strong> Regensburg<br />

2. Novartis Pharma GmbH<br />

3. University <strong>of</strong> Ulm<br />

Objective & Purpose: Elevated blood-glucose levels in diabetes mellitus (DM)<br />

boost the development <strong>of</strong> secondary diseases complications <strong>of</strong> the eye such<br />

as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR).<br />

In DM diverse biomechanisms and processes as well as cytokine levels are<br />

altered. Therefore several cytokine- and apolipoprotein-levels (i.e. biomarkers)<br />

are measured to assess correlation <strong>of</strong> biomarkers with baseline characteristics<br />

and with outcome.<br />

Methods: In a phase III clinical trial patients with visual impairment due to DME<br />

were randomized 2:1 for treatment <strong>of</strong> ranibizumab in combination with laser<br />

photocoagulation or laser photocoagulation alone up to 12 month. At baseline<br />

visits and at defined study time points serum and plasma samples were taken,<br />

aliquoted and stored at -18°C until investigation. Levels <strong>of</strong> IL-6, MCP-1, ICAM-<br />

1, VCAM-1, IL-8, IL-10, IL 17a, VEGF, Apo Al, Apo All, Apo Cll, Apo Clll, Apo E<br />

and Apo B100 are determined by ELISA or Luminex.<br />

Results: Approximately 125 patients were randomized with LPLV early July<br />

2011.<br />

Conclusion: The assessment evaluates the correlation between biomarkers<br />

and central retinal thickness at baseline and as main outcome parameter.<br />

<strong>WOC</strong><strong>2012</strong> Abstract Book<br />

PO-IMM-15<br />

Case Report: Resistant Corneal Ulcer diagnosed by Histopathology<br />

as Acanthamoeba Keratitis.<br />

Al Mansoori Noura (1) , Al Obthani Murad (1) , Dachiw Christine (1) , Hendawy<br />

Bassem (1) , Al Mosabi Saleh (1)<br />

1. Sheikh Khalifa Medical City<br />

Purpose and<br />

Methods: Case report <strong>of</strong> Acanthamoeba Keratitis in middle-aged farmer whose<br />

corneal scraping slides and cultures where negative for 3 times. However,<br />

histopathology <strong>of</strong> corneal biopsy showed the organism. Case Report: A 48<br />

years old male farmer presented to the first hospital with history <strong>of</strong> exposure<br />

to water, soil and grass. Initial scraping, showed hyphae in fungal slides but<br />

cultures were negative. Treated for 3 weeks as fungal ulcer with systemic<br />

Voricanazole, natamycin, and Voricanazole drops. Patient didn›t respond to<br />

therapy and infiltrate size increased and referred to our service for further<br />

management. Visual acuity on presentation was Hand Motion. Re-culture<br />

was negative and patient deteriorated more over one week. Corneal biopsy<br />

cultures where negative and Histopathology showed the organism. The<br />

patient was treated with Porpamidine and chlorhexadine drops. Infiltrate size<br />

decreased and hypopyon disappeared and visual acuity improved over one<br />

week to counting finger.<br />

Conclusion: This case emphasizes the importance <strong>of</strong> considering<br />

acanthamoeba species in the differential diagnosis <strong>of</strong> keratitis. In late stage,<br />

Acanthamoeba cysts present in deep stroma and might not be detect by<br />

scraping. Histopathological evaluation <strong>of</strong> corneal biopsy was crucial in<br />

diagnosing the case reported.<br />

PO-IMM-16<br />

Acanthamoeba Infections Initiate Toll-Like Receptor 4 Expression<br />

and Inflammatory Responses in the Corneal Epithelium<br />

Alizadeh Hassan (1) , LI Haochuan (2) , Neelam Sudha (1)<br />

1. Department <strong>of</strong> Cell Biology and Anatomy, North Texas Eye Research Institute<br />

2. Department <strong>of</strong> Ophthalmology, University <strong>of</strong> Texas Southwestern Medical<br />

Center<br />

Purpose: To determine if Toll-like receptors (TLRs) on corneal epithelial cells<br />

are activated by Acanthamoeba,<br />

Methods: The expression <strong>of</strong> mRNA for TLR1, TLR2, TLR3, TLR4, and TLR9 in<br />

normal and A. castellanii infected human corneal epithelial (HCE) cells were<br />

examined by RT-PCR. Secretion <strong>of</strong> IL-8 IL-6, and MIP-2 was examined by<br />

ELISA. Chinese hamsters were infected with pathogenic A. castellanii and<br />

non-pathogenic A. castellanii neff strains <strong>of</strong> Acanthamoeba trophozoites. The<br />

expression <strong>of</strong> TLR1s genes was examined by RT-PCR.<br />

Results: HCE cells constitutively expressed TLRs mRNA, and A. castellanii<br />

upregulated TLR2 and TLR4 transcription. Both IL-6 and IL-8 mRNA expression<br />

was upregulated in HCE cells exposed to A. castellanii trophozoites. A.<br />

castellanii trophozoites and LPS induced significant IL-8 production by HCE<br />

cells as measured by ELISA. Clinical isolates <strong>of</strong> Acanthamoeba but not soil<br />

isolates activate TLR4 expression in the Chinese hamster corneas, while TLR2<br />

expression was unchanaged..Clinical isolate induced significant (P

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