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2. Contributors

Author

Abu-Shakra, Mahmoud, primary, Adiguzel, Yekbun, additional, Al Shawaf, Maisam, additional, Alghory, Amal, additional, Almeida, Isabel, additional, Alrais, Mahmoud, additional, Alrifaai, Mohamad Aosama, additional, Alwani, Abdulkarim, additional, Alwani, Abdulrahman, additional, Amital, Howard, additional, Anna, Dubaniewicz, additional, Arleevskaya, Marina, additional, Ashkenazi, Shai, additional, Athanassiou, Lambros, additional, Athanassiou, Panagiotis, additional, Atik, Houda, additional, Atzeni, Fabiola, additional, Balbir-Gurman, Alexandra, additional, Balcioglu, Zeynep Betul, additional, Baldini, Chiara, additional, Barbour, Mohammad, additional, Bashi, Tomer, additional, Belyaeva, Irina V., additional, Ben-Ami, Dana, additional, Blank, Miri, additional, Boccassini, Laura, additional, Bogdanos, Dimitrios P., additional, Bombardieri, Stefano, additional, Bost, Chloé, additional, Brandão, Mariana, additional, Braun-Moscovici, Yolanda, additional, Brooks, Wesley H., additional, Campar, A., additional, Carvalheiras, Graziela, additional, Cervera, R., additional, Churilov, Leonid P., additional, Cohen, Eytan, additional, Correia, J., additional, Darkhabani, Mohammad, additional, David, Paula, additional, de Carvalho, Jozélio Freire, additional, Deniz, Omer Faruk, additional, Detrick, Barbara, additional, Deutsch, Melanie, additional, Di Battista, Marco, additional, Dogan, Emir, additional, Dogru, Omer Faruk, additional, Domingues, Vital Da Silva, additional, Dotan, Arad, additional, Dow, Coad Thomas, additional, Durai, Malarvizhi, additional, Elefante, Elena, additional, Elsalti, Abdulrahman, additional, Erman, Mikhail V., additional, Esirgun, Sevval Nil, additional, Ferrão, C., additional, Ferreira, Álvaro, additional, Ferro, Francesco, additional, Fonseca, Tomás, additional, Garg, Ravindra Kumar, additional, Guilherme, Luiza, additional, Habra, Mona, additional, Halpert, Gilad, additional, Hammerstad, Sara Salehi, additional, Hooks, John J., additional, Ilchovska, Daisy, additional, Invernizzi, Pietro, additional, Israeli, E., additional, Janket, Sok-Ja, additional, Kalil, Jorge, additional, Karaoglan, Birnur Sinem, additional, Kiyak, Zeynep, additional, Kol, Mustafa Yusuf, additional, Kostoglou-Athanassiou, Ifigenia, additional, Krause, Ilan, additional, Kudryavtsev, Igor V., additional, Kumar, Neeraj, additional, Lavine, Noy, additional, Lerman, Tsahi T., additional, Levi, Assi, additional, Ling, Eduard, additional, Moutsopoulos, Haralampos M., additional, Mahajna, Hussein, additional, Mahroum, Naim, additional, Malhotra, Hardeep Singh, additional, Malkova, Аnna M., additional, Maoz-Segal, Ramit, additional, Marinho, António, additional, Mavragani, Clio P., additional, Meurman, Jukka H., additional, Milhes, Jean, additional, Mimouni, Daniel, additional, Morais, Cátia Iracema, additional, Moudgil, Kamal D., additional, Muniz Caldas, Cezar Augusto, additional, Neves, Esmeralda, additional, Neyestani, Kamyar, additional, Nikolaev, Alexei V., additional, Noversa de Sousa, Rita, additional, Ohayon, Aviran, additional, Palumbo, Antonino, additional, Pasoto, Sandra Gofinet, additional, Petríková, Jana, additional, Puxeddu, Ilaria, additional, Raftopoulou, Sylvia, additional, Renaudineau, Yves, additional, Ribeiro, Francinne Machado, additional, Rigopoulou, Eirini I., additional, Rosário, Cristina, additional, Rossa, Alessandra Della, additional, Sahin, Meyha, additional, Sarzi-Puttini, Piercarlo, additional, Seguro, Luciana Parente Costa, additional, Seida, Isa, additional, Seida, Ravend, additional, Serpa Pinto, L., additional, Sharon, Eran, additional, Shoenfeld, Yehuda, additional, Smyk, Daniel S., additional, Sousa, Rita Catarina Medeiros, additional, Starshinova, Anna A., additional, Tamimi, Faleh, additional, Tocut, Milena, additional, Tomer, Yaron, additional, Tunitsky-Lifshitz, Yulia, additional, Vasconcelos, Carlos, additional, Vasconcelos, Júlia, additional, Vassilopoulos, Dimitrios, additional, Venkatesha, Shivaprasad H., additional, Villanueva, Ronald, additional, Vita, Pedro, additional, Yablonskiy, Piotr K., additional, Yilmaz, Mesut, additional, Zamorano, Bryan, additional, Zandman-Goddard, Gisele, additional, Zinchenko, Yulia S., additional, and Zoubi, Magdi, additional

Published
2024
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5. Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

Author

Fox, Austin R, Gordon, Lynn K, Heckenlively, John R, Davis, Janet L, Goldstein, Debra A, Lowder, Careen Y, Nussenblatt, Robert B, Butler, Nicholas J, Dalal, Monica, Jayasundera, Thiran, Smith, Wendy M, Lee, Richard W, Adamus, Grazyna, Chan, Chi-Chao, Hooks, John J, Morgans, Catherine W, Detrick, Barbara, and Sen, H Nida

Subjects
Clinical Research, Eye Disease and Disorders of Vision, Autoantibodies, Autoantigens, Autoimmune Diseases, Consensus, Delphi Technique, Humans, Paraneoplastic Syndromes, Ocular, Retina, Retinal Diseases, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services, Ophthalmology & Optometry
Abstract

PurposeTo develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts.DesignModified Delphi process.MethodsA survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement.ResultsThere was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies.ConclusionsConsensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Published
2016

7. Urinary IL‐6 and IL‐8 as predictive markers in bladder urothelial carcinoma: A pilot study.

Author

VandenBussche, Christopher J., Heaney, Christopher D., Kates, Max, Hooks, John J., Baloga, Kelly, Sokoll, Lori, Rosenthal, Dorothy, and Detrick, Barbara

Abstract

Background: Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear. Methods: Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL‐8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL‐6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations. Results: Significantly elevated concentrations of IL‐6 and IL‐8 were detected in the urine from patients with urothelial carcinoma on follow‐up compared to patients with benign follow‐up. The presence of both IL‐6 and IL‐8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow‐up. The presence of the combination of both IL‐6 and IL‐8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL‐6 and IL‐8 concentrations in the urine from patients with HGUC vs. the hematuria cohort. Conclusions: The presence of IL‐6 and IL‐8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory. Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. The authors show that a combination of two regulatory molecules, IL‐6 and IL‐8, are present in 100% of patients with high‐grade bladder cancer, whereas this dual combination signature was observed in only 13.6% of patients with hematuria and without any diagnosis of urothelial carcinoma on follow‐up. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Contributors

Author

Abdurakhmanov, Alexander, primary, Abu-Shakra, Mahmoud, additional, Afanasyeva, Marina, additional, Agmon-Levin, Nancy, additional, Albert, Paul J., additional, Almeida, Isabel, additional, Alves, Rute, additional, Amital, Howard, additional, Andrade, Paulo, additional, Antonelli, Alessandro, additional, Puccetti, Antonio, additional, Arango, María-Teresa, additional, Atzeni, Fabiola, additional, Baird, Alison E., additional, Balbir-Gurman, Alexandra, additional, Bashi, Tomer, additional, Batticciotto, Alberto, additional, Benucci, Maurizio, additional, Blank, Miri, additional, Bogdanos, Dimitrios P., additional, Bombardieri, S., additional, Borella, E., additional, Bosis, Samantha, additional, Bournia, Vasiliki Kalliopi, additional, Brandão, Mariana, additional, Braun-Moscovici, Yolanda, additional, Brender-Gotlieb, Neta, additional, Cainelli, Francesca, additional, Caldas, Cezar Augusto Muniz, additional, Campar, A., additional, Carvalheiras, Graziela, additional, Cervera, R., additional, Chapman, Joab, additional, Chastain, Emily M.L., additional, Claudio, Lunardi, additional, Cohen, Eytan, additional, Conti, Fabrizio, additional, Correia, J., additional, Carvalho, Jozélio Freire de, additional, Rossa, A. Della, additional, Detrick, Barbara, additional, Deutsch, Melanie, additional, Di Domenicantonio, Andrea, additional, Domeneghetti, M., additional, Domingues, Vital, additional, Doria, A., additional, Dow, Coad Thomas, additional, Dreyfus, David H., additional, Drouin, Elise E., additional, Dubaniewicz, Anna, additional, Durai, Malarvizhi, additional, Ebringer, Alan, additional, Ehrenfeld, Michael, additional, Elisa, Tinazzi, additional, Esposito, Susanna, additional, Fallahi, Poupak, additional, Faria, Raquel, additional, Farinha, Fátima, additional, Ferrannini, Ele, additional, Ferrari, Silvia Martina, additional, Ferreira, Alvaro, additional, Ferrão, C., additional, Garg, Ravindra Kumar, additional, Gatto, M., additional, Ghirardello, A., additional, Giovanna, Zanoni, additional, Giuseppe, Patuzzo, additional, Givaty, Gili, additional, Guilherme, Luiza, additional, Hammerstad, Sara Salehi, additional, Hodak, Emillia, additional, Hooks, John J., additional, Iaccarino, L., additional, Invernizzi, Pietro, additional, Israeli, Eitan, additional, Jamin, Christophe, additional, Janket, Sok-Ja, additional, Jarčuška, Peter, additional, Jones, Rodney P., additional, Kalil, Jorge, additional, Kanasi, Eleni, additional, Kivity, Shaye, additional, Konikoff, Tom, additional, Kozáková, D., additional, Krause, Ilan, additional, Lerner, Aaron, additional, Lidar, Merav, additional, Ling, Eduard, additional, Mahajna, Hussein, additional, Mahroum, Naim, additional, Maoz-Segal, Ramit, additional, Marinho, António, additional, Marshall, Trevor G., additional, Martinelli, Maria, additional, Marzia, Dolcino, additional, Mavragani, Clio P., additional, Mendonça, Teresa, additional, Miller, Stephen D., additional, Mimouni, Daniel, additional, Monteiro, Marta, additional, Moudgil, Kamal D., additional, Moulton, Vaishali R., additional, Moutsopoulos, Haralampos M., additional, Nagpal, Kamalpreet, additional, Neves, Esmeralda, additional, Nussenblatt, Robert, additional, Ollech, Ayelet, additional, Palma, L., additional, Pasoto, Sandra Gofinet, additional, Pella, Daniel, additional, Pereira, Cláudia, additional, Perricone, Carlo, additional, Petríková, Jana, additional, Proal, Amy D., additional, Rashid, Taha, additional, Reif, Shimon, additional, Renaudineau, Yves, additional, Ribeiro, Francinne Machado, additional, Rigante, Donato, additional, Rigopoulou, Eirini I., additional, Rose, Noel R., additional, Rosário, Cristina, additional, Rovenský, J., additional, Sakkas, Lazaros I., additional, Sarzi-Puttini, Piercarlo, additional, Seguro, Luciana Parente Costa, additional, Semino, Margherita, additional, Shoenfeld, Yehuda, additional, Silva, S., additional, Simonin, Laurent, additional, Smyk, Daniel S., additional, Sousa, Rita Catarina Medeiros, additional, Stagnaro, C., additional, Steere, Allen C., additional, Strle, Klemen, additional, Tektonidou, Maria G., additional, Tishler, Moshe, additional, Tomer, Yaron, additional, Toubi, Elias, additional, Tsokos, George C., additional, Vadasz, Zahava, additional, Valesini, Guido, additional, Vasconcelos, Carlos, additional, Vasconcelos, Júlia, additional, Vassilopoulos, Dimitrios, additional, Venkatesha, Shivaprasad H., additional, Vento, Sandro, additional, Viale, Christophe, additional, Villanueva, Ronald, additional, Vita, Pedro, additional, Wilson, Clyde, additional, Youinou, Pierre, additional, Záňová, E., additional, Zandman-Goddard, Gisele, additional, and Zen, M., additional

Published
2015
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17. The RPE Cell and the Immune System

Author

Detrick, Barbara and Hooks, John J.

Subjects
Innate immunity, Inflammation, Antigen presenting cell, animal diseases, Adaptive immunity, bacteria, Cytokines, chemical and pharmacologic phenomena, sense organs, biochemical phenomena, metabolism, and nutrition, Article
Abstract

The RPE cell plays a pivotal role in retinal immunity. In fact, the RPE cell orchestrates both innate and adaptive immunity and contains a plethora of factors to regulate the immune response. Many immunoregulatory activities of the RPE cell are accomplished through cytokine production, toll-like receptor (TLR) activation, complement regulation and antigen presentation. The RPE cells immune regulatory network plays an essential role in retinal immunity and autoimmunity, retinal infections and in a variety of retinal degenerative disorders. Understanding the immune regulatory properties of this cell may provide additional clues to disease mechanisms that may lead to future treatments for many human retinal diseases.

Published
2019

28. List of Contributors

Author

Abu-Shakra, Mahmoud, primary, Achiron, Anat, additional, Adelman, Miranda K., additional, Afanasyeva, Marina, additional, Akaogi, Jun, additional, Alcocer-Varela, Jorge, additional, Amedei, Amedeo, additional, Appelmelk, Ben J., additional, Aron-Maor, Anabel, additional, Asherson, Ronald A., additional, van den Berg, Leonard H., additional, Bergman, Mathijs P., additional, Blank, M., additional, Bombardieri, Stefano, additional, Buc, Milan, additional, Bussel, James, additional, Cainelli, Francesco, additional, Cervera, Ricard, additional, Chou, Alexander J., additional, Cohen, Irun R., additional, Cohen, Pascal, additional, Acuña, J.C. Crispin, additional, Cunha-Neto, Edecio, additional, Cutolo, Maurizio, additional, David, Michael, additional, D'Elios, Mario M., additional, Del Prete, Gianfranco, additional, Denman, A.M., additional, Detrick, Barbara, additional, Doria, Andrea, additional, Dugué, C., additional, Durai, Malarvizhi, additional, Ebringer, Alan, additional, Eisenstein, Miriam, additional, Ferri, Clodoveo, additional, Frostegård, Johan, additional, Gambari, Pier Franca, additional, Garvey, Marjorie A., additional, Gershwin, M. Eric, additional, Ghirardello, Anna, additional, Giacomelli, Roberto, additional, Guiducci, Serena, additional, Fonseca, Simone Gonçalves, additional, Guilherme, Luiza, additional, Guillevin, Loïc, additional, Hafler, David A., additional, Hatemi, Gülen, additional, He, Xiao-Song, additional, Hooks, John J., additional, Iaccarino, Luca, additional, Jacobson, Steven, additional, Jansen, M.D., additional, Jara, Luis J., additional, Jun, Hee-Sook, additional, Kalil, Jorge, additional, Kapsogeorgou, Efstathia K., additional, Iwai, Leo Kei, additional, Kelly, Kindra M., additional, Krause, Ilan, additional, Krebs, Philippe, additional, Kuroda, Yoshiki, additional, Lerner, Aaron, additional, Liakos, Dimitrios A., additional, Lim, Dong-Gyun, additional, Ludewig, Burkhard, additional, Marchalonis, John J., additional, Cerinic, Marco Matucci, additional, Medina, Gabriela, additional, Miller, Stephen D., additional, Milo, Gui, additional, Mimouni, Daniel, additional, Miranda, Juan M., additional, Bilate, Angelina Morand B., additional, Moudgil, Kamal D., additional, Moutsopoulos, Haralampos M., additional, Nacionales, Dina C., additional, Navarro, Carmen, additional, Nussenblatt, Robert, additional, Pagnoux, Christian, additional, Pender, Michael P., additional, Pers, Jaques-Olivier, additional, van der Pol, W-Ludo, additional, Prummel, Mark F., additional, Quintana, Francisco J., additional, Rager-Zisman, B., additional, Rashid, Taha, additional, Reeves, Westley H., additional, Reif, Shimon, additional, Renaudineau, Yves, additional, Rose, Noel R., additional, Rovenský, Jozef, additional, Satoh, Minoru, additional, Schmidt, Reinhold E., additional, Seriolo, Bruno, additional, Severin, Marianne C., additional, Shoenfeld, Yehuda, additional, Sibilia, Jean, additional, Snider, Lisa A., additional, Soldan, Samantha S., additional, Sorge, N.M. van, additional, Steere, Allen C., additional, Stoll, Matthias, additional, Sulli, Alberto, additional, Swedo, Susan E., additional, Tishler, Moshe, additional, Tomer, Yaron, additional, Tyndall, Alan, additional, Vandenbroucke-Grauls, Christina M., additional, VanderLugt-Castaneda, Carol L., additional, Vassilopoulos, Dimitrios, additional, Vento, Sandro, additional, Vera-Lastra, Olga, additional, Villanueva, Ronald, additional, Wachsmann, Dominique, additional, Weinstock, Joel V., additional, Wick, Georg, additional, Wiersinga, Wilmar M., additional, Wilson, Clyde, additional, van de Winkel, Jan G.J., additional, Wucherpfennig, Kai W., additional, Xu, Qingbo, additional, Yazici, Hasan, additional, Yocum, David E., additional, Yoon, Ji-Won, additional, Youinou, Pierre, additional, Zampieri, Sandra, additional, and Zandman-Goddard, Gisele, additional

Published
2004
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33. Differential regulation of microRNA-146a and microRNA-146b-5p in human retinal pigment epithelial cells by interleukin-1β, tumor necrosis factor-α, and interferon-γ

Author

Kutty, R. Krishnan, Nagineni, Chandrasekharam N., Samuel, William, Vijayasarathy, Camasamudram, Jaworski, Cynthia, Duncan, Todd, Cameron, Jennifer E., Flemington, Erik K., Hooks, John J., and Redmond, T. Michael

Subjects
Adult, Time Factors, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, Gene Expression Profiling, Interleukin-1beta, Molecular Sequence Data, Electrophoretic Mobility Shift Assay, Epithelial Cells, Retinal Pigment Epithelium, Models, Biological, Interferon-gamma, MicroRNAs, Interleukin-1 Receptor-Associated Kinases, STAT1 Transcription Factor, Gene Expression Regulation, Humans, Inflammation Mediators, Promoter Regions, Genetic, Research Article
Abstract

Purpose The inflammatory response of the retinal pigment epithelium (RPE) is implicated in the pathogenesis of age-related macular degeneration. The microRNAs miR-146a and miR-146b-5p can regulate the inflammatory process by attenuating cytokine signaling via the nuclear factor-κB pathway. The aim of the present study is to investigate the expression of miR-146a and miR-146b-5p in human RPE cells and their response to proinflammatory cytokines. Methods Confluent cultures of RPE cells established from adult human donor eyes were treated with the proinflammatory cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. The expression of microRNAs was analyzed by real-time PCR using total RNA fraction. The retinal pigment epithelial cell line ARPE-19 was employed to analyze the promoter activity of the genes encoding miR-146a and miR-146b-5p. STAT1-binding activity of oligonucleotides was analyzed by electrophoretic mobility shift assay. ARPE-19 cells were transiently transfected with miR-146a and miR-146b-5p mimics for the analysis of IRAK1 expression by western immunoblotting. Results Real-time PCR analysis showed that miR-146a and 146b-5p are expressed in RPE cells. The cells responded to proinflammatory cytokines (IFN-γ + TNF-α + IL-1β) by highly increasing the expression of both miR-146a and miR-146b-5p. This was associated with an increase in the expression of transcripts for CCL2, CCL5, CXCL9, CXCL10, and IL-6, and a decrease in that for HMOX1. The miR-146a induction was more dependent on IL-1β, since its omission from the cytokine mix resulted in a greatly reduced response. Similarly, the induction of miR-146b-5p was more dependent on IFN-γ, since its omission from the cytokine mix minimized the effect. In addition, the increase in MIR146B promoter activity by the cytokine mix was effectively blocked by JAK inhibitor 1, a known inhibitor of the JAK/STAT signaling pathway. The expression of IRAK1 protein was decreased when ARPE-19 cells were transiently transfected with either miR-146a mimic or miR-146b-5p mimic. Conclusions Our results clearly show that both miR-146a and miR-146b-5p are expressed in human RPE cells in culture and their expression is highly induced by proinflammatory cytokines (IFN-γ + TNF-α + IL-1β). The induction of miR-146a showed a dependency on IL-1β, while that of miR-146b-5p on IFN-γ. Our results show for the first time that miR-146b-5p expression is regulated by IFN-γ, potentially via the JAK/STAT pathway. These two microRNAs could play a role in inflammatory processes underlying age-related macular degeneration or other retinal degenerative diseases through their ability to negatively regulate the nuclear factor-κB pathway by targeting the expression of IRAK1.

Published
2013

34. Infections Associated with Retinal Autoimmunity

Author

Detrick, Barbara, Hooks, John J., and Nussenblatt, Robert

Subjects
Onchocerca volvulus, parasitic diseases, Experimental coronavirus retinopathy, Retinal autoimmunity, Toxoplasmosis gondii, Article
Abstract

Autoimmune reactivity and autoimmune disease in the eye is a rapidly expanding area of research and therapy. We present evidence implicating three distinct classes of infectious agents in the development of an autoimmune process within the retina. We highlight two human diseases triggered by Onchocerca volvulus or Toxoplasma gondii and an experimental model of retinal degenerative disease, referred to as experimental coronavirus retinopathy (ECOR). Analysis of these systems revealed distinct pathogenic mechanisms involved in the induction of autoimmunity triggered by each organism. In T. gondii infections, the chronic reactivation is probably responsible for the presentation of sequestered retinal epitopes of the immune system. In O. volvulus infections, molecular mimicry between the organism and the human RPE protein may contribute to retinal pathology. In ECOR, differences in time of induction, duration, and intensity of innate immune reactivity may contribute to autoimmune reactivity in BALB/c mice.

Published
2007

35. Reply

Author

Fox, Austin R., primary, Gordon, Lynn K., additional, Heckenlively, John R., additional, Davis, Janet L., additional, Goldstein, Debra A., additional, Lowder, Careen Y., additional, Nussenblatt, Robert B., additional, Butler, Nicholas J., additional, Dalal, Monica, additional, Jayasundera, Thiran, additional, Smith, Wendy M., additional, Lee, Richard W., additional, Adamus, Grazyna, additional, Chan, Chi-Chao, additional, Hooks, John J., additional, Morgans, Catherine W., additional, Detrick, Barbara, additional, and Sen, H. Nida, additional

Published
2016
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36. Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

Author

Fox, Austin R., primary, Gordon, Lynn K., additional, Heckenlively, John R., additional, Davis, Janet L., additional, Goldstein, Debra A., additional, Lowder, Careen Y., additional, Nussenblatt, Robert B., additional, Butler, Nicholas J., additional, Dalal, Monica, additional, Jayasundera, Thiran, additional, Smith, Wendy M., additional, Lee, Richard W., additional, Adamus, Grazyna, additional, Chan, Chi-Chao, additional, Hooks, John J., additional, Morgans, Catherine W., additional, Detrick, Barbara, additional, and Sen, H. Nida, additional

Published
2016
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42. Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration.

Author

Nagineni, Chandrasekharam N., Kommineni, Vijay K., Ganjbaksh, Nader, Nagineni, Krishnasai K., Hooks, John J., and Detrick, Barbara

Subjects
CHEMOKINE receptors, NEOVASCULARIZATION, RETINAL degeneration
Abstract

Chemokine reeptor-3 (CCR-3) was shown to be associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). AMD is a vision threatening retinal disease that affects the aging population world-wide. Retinal pigment epithelium and choroid in the posterior part of the retina are the key tissues targeted in the pathogenesis of CNV in AMD. We used human retinal pigment epithelial (HRPE) and choroidal fibroblast (HCHF) cells, prepared from aged adult human donor eyes, to evaluate the expression of major CCR-3 ligands, CCL-5, CCL -7, CCL-11,CCL-24 and CCL-26. Microarray analysis of gene expression in HRPE cells treated with inflammatory cytokine mix (ICM= IFN-γ+TNF-α+IL-1β) revealed 75 and 23-fold increase in CCL-5 and CCL-7 respectively, but not CCL-11, CCL-24 and CCL-26. Chemokine secretion studies of the production of CCL5 and CCL7 by HRPE corroborated with the gene expression analysis data. When the HRPE cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent manner. Similar to the gene expression data, the ICM did not enhance HRPE production of CCL-11, CCL-24 and CCL-26. CCL-11 and CCL-26 were increased with IL-4 treatment and this HRPE production was augmented in the presence of TNF-α and IL1α. When HCHF cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent fashion. IL-4 induced low levels of CCL-11 and CCL-26 in HCHF and this production was significantly enhanced by TNF-α. Under these conditions, neither HRPE nor HCHF were demonstrated to produce CCL-24. These data demonstrate that chronic inflammation triggers CCL-5 and CCL-7 release by HRPE and HCHF and the subsequent interactions with CCR3 may participate in pathologic processes in AMD. [ABSTRACT FROM AUTHOR]

Published
2015
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49. Reply

Author

Forooghian, Farzin, primary, Macdonald, Ian M., additional, Heckenlively, John R., additional, Héon, Elise, additional, Gordon, Lynn K., additional, Hooks, John J., additional, Detrick, Barbara, additional, and Nussenblatt, Robert B., additional

Published
2009
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