Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Taurone, Samanta (2016) Profilo Immunoistochimico di Citochine Infiammatorie e Fattori di Crescita nell'Occhio Umano. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF
3183Kb

Abstract (inglese)

The aim of this experimental thesis focuses on the study of eye diseases related to the involvement of growth factors, of inflammatory cytokines in chronic-inflammatory, and of tissue remodeling. Particular emphasis has been addressed to the physiopathology of the eye surface and the complex relationships existing between cells and mediators in the immune response. Furthermore, the research has been directed to molecular events that control these biological responses. The lost in regulation of the inflammatory processes corresponds to the loss of control of the production/action of cytokines followed by the onset of inflammatory or autoimmune pathologies.
Immunohistochemical technique has been performed in order to evaluate the physiopathological behaviour of inflammatory cytokines and of some growth factors (TGF-b1, IL-1b, IL-6, TNF-a and VEGF) located in the ocular tissues. Samples were obtained from human patients affected by glaucoma, diabetic retinopathy and macular degeneration. Our main purpose was to assess the levels of expression and localization of pro-inflammatory cytokines by immunohistochemistry in order to identify their involvement in the pathology, assuming for them a role in the modulation of these factors as a potential therapeutic target. Our study has shown an imbalance between pro- and anti-inflammatory cytokine plays a key role in the pathogenesis of retinal diseases. This disproportion within a complex regulatory network is related to some immunological processes that promote autoimmunity, chronic inflammation and / or tissue destruction. We were able to confirm that the inflammatory process involves a complex cascade of molecular and cellular biological signals, altering the physiological responses of the ocular tissues. The transmission electron microscopy investigation (TEM) showed that at the site of the lesion cells the probable release of molecular signals produces changes in the affected area: dilation of blood vessels resulting in increased blood flow and vascular permeability, exudation of fluid containing proteins such as immunoglobulins and invasion by leukocytes. It is well known that chronic and prolonged inflammation is a fundamental feature in some diseases such as atherosclerosis, obesity, diabetes, rheumatoid arthritis, asthma and various types of cancer. These diseases are strictly connected with their ocular manifestations: diabetic retinopathy, scleritis, uveitis, dry eye syndrome and ocular tumours. It should be noticed that pharmacological and clinical advances occur in areas apparently distant from application in ophthalmology, but they should be potentially used also in the ocular field by a translational application. Since many ocular tissues have a immune-privileged system to protect the delicate visual apparatus, the control of the acute inflammation is regulated by the same pathways and mediators that manage inflammatory responses in other organs. These scientific informations not only provide further support to the chronic inflammation, that plays a significant role in the pathogenesis of diabetic retinopathy, but also suggest that the inflammatory process is active even before retinopathy (diabetic and/or proliferative) is clinically diagnosed. Therefore, the alteration of the profile of some cytokines might be useful both as a predictive marker as well as an important target for the development of new therapeutic treatments.
A novel pharmacological approach to treat eye inflammation may be represented by progress in the cellular therapy. In recent years, research has been devoted to the development of cell therapy applied to eye diseases producing a remarkably increased risk of visual impairment. Recently, cellular therapy has evolved into two research pathways: one finalized to a remodeling of the structure and the relative functions of specific tissues using stem cells; the other one has been focused on the restore of the immunological homeostasis controlling the harmful effects caused by inflammatory diseases.

Abstract (italiano)

Questo lavoro di tesi sperimentale è rivolto allo studio di alcune patologie oculari e al coinvolgimento di alcuni fattori di crescita e citochine infiammatorie in alcune condizioni cronico-infiammatorie e nel rimodellamento tissutale, con particolare interesse per la fisiopatologia della superficie oculare e al legame complesso tra cellule e mediatori nella risposta immune innata ed acquisita. Nello svolgimento dell’attività di ricerca particolare interesse è stato rivolto agli eventi molecolari deputati al controllo e allo spegnimento di queste risposte biologiche. La mancata regolazione dei processi infiammatori corrisponde infatti alla perdita del controllo della produzione/azione delle citochine e determina come conseguenza l’insorgere di patologie infiammatorie croniche o autoimmuni. In questo lavoro di tesi è stato valutato, mediante l'utilizzo della tecnica immunoistochimica, il ruolo fisiopatologico di alcune citochine infiammatorie e di alcuni fattori di crescita (TGF-b1, IL-1b, IL-6, TNF-a e VEGF) in tessuti oculari umani ottenuti da pazienti affetti da glaucoma, retinopatia diabetica ed degenerazione maculare in confronto ad analoghi tessuti umani normali. Pertanto il nostro principale scopo è stato quello di valutare i livelli di espressione e la localizzazione delle citochine pro-infiammatorie mediante tecnica immunoistochimica in modo da poter identificare il loro coinvolgimento nella patologia ipotizzando per esse un ruolo nella modulazione di tali fattori come potenziale bersaglio terapeutico. Come dimostrato nel nostro studio uno sbilanciamento tra citochine pro- e anti-infiammatorie giuoca un ruolo fondamentale nella patogenesi delle patologie retiniche. Tale sbilanciamento nell’ambito di un complesso network regolatorio è correlato ad alcuni processi immunologici che favoriscono autoimmunità, infiammazione cronica e/o distruzione tissutale. Nello svolgimento del lavoro di tesi è stato ulteriormente confermato come il processo infiammatorio comporti una complessa cascata di segnali biologici molecolari e cellulari, che alterano le risposte fisiologiche del tessuto oculare interessato. L'analisi in microscopia elettronica (TEM) ha evidenziato come presso il sito della lesione le cellule rilascino verosimilmente segnali molecolari che causano una serie di modificazioni nella zona interessata: dilatazione dei vasi sanguigni, con conseguente aumento del flusso sanguigno e della permeabilità vascolare, essudazione di liquidi contenenti proteine come le immunoglobuline ed invasione da parte dei leucociti. Risulta ampiamente noto come l’infiammazione cronica e prolungata sia una caratteristica determinante per malattie come aterosclerosi, obesità, diabete, artrite reumatoide, asma e diversi tipi di tumore. Molte di queste malattie si caratterizzano per una ormai consolidata manifestazione oculare: retinopatia diabetica, sclerite, uveite, sindrome dell’occhio secco e neoplasie oculari. Questo ci porta ad osservare attentamente anche i progressi farmacologici e clinici che si registrano in aree apparentemente distanti dall’applicazione in campo oftalmologico, ma che potenzialmente, per traslazione, potrebbero essere utilizzabili in prospettiva anche in campo oculare. Infatti, nonostante molti tessuti oculari abbiano un sistema immuno-privilegiato o altamente evoluto per proteggere il delicato apparato visivo, l’indispensabile controllo dell’infiammazione acuta è regolato dalle stesse vie generali e da mediatori e cellule effettrici che gestiscono le risposte infiammatorie in altri organi. Queste informazioni scientifiche non soltanto conferiscono ulteriore supporto al fatto che l’infiammazione cronica svolga un ruolo significativo nella patogenesi della retinopatia, ma suggeriscono, inoltre, che il processo infiammatorio si attivi prima ancora che la retinopatia (diabetica e/o proliferativa) sia clinicamente diagnosticata. L’alterazione nel profilo di alcune citochine potrebbe, quindi, diventare sia un marker predittivo, che un importante target per lo sviluppo di future opzioni terapeutiche.
Un percorso radicalmente diverso dall’approccio farmacologico nella cura delle patologie infiammatorie oculari potrebbe in futuro essere rappresentato dai progressi dalla terapia cellulare. Negli ultimi anni si è evidenziato un crescente interesse per la possibile applicazione della terapia cellulare ad alcune patologie oculari che incidono maggiormente sul rischio di disabilità visiva. La terapia cellulare si può dividere in due ampie classi: una, attraverso l’impiego di cellule staminali, finalizzata al rimodellamento della struttura e della relativa funzionalità di specifici tessuti e cellule; l’altra, che utilizza cellule immunitarie nel ruolo di potenziali immunomodulatori dell’infiammazione, diretta al ripristino dell’omeostasi immunologica attraverso il controllo degli effetti nocivi provocati dalle patologie infiammatorie.

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Di Liddo , R
Dottorato (corsi e scuole):Ciclo 28 > Scuole 28 > BIOMEDICINA > MEDICINA RIGENERATIVA
Data di deposito della tesi:22 Gennaio 2016
Anno di Pubblicazione:Febbraio 2016
Parole chiave (italiano / inglese):occhio, retinopatia diabetica, glaucoma, fattori di crescita, citochine infiammatorie
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/08 Anatomia patologica
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina Molecolare
Codice ID:9087
Depositato il:06 Ott 2016 14:34
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

- Abbas AK, Lichtman AH, Pillai S. Immunologia cellulare e molecolare, 6° edizione, Milano 2010, Elsevier Masson. Cerca con Google

- Abbas AK, Lichtman AH, Pober JS. Cellular and molecular immunology, 2000, W.B. Saunders Company. Cerca con Google

- Abcouwer SF, Gardner TW. Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment. Ann N Y Acad Sci. 2014 Apr;1311(1):174-90. Cerca con Google

- Abcouwer SF. Angiogenic Factors and Cytokines in Diabetic Retinopathy. J Clin Cell Immunol. 2013;Suppl 1(11). Cerca con Google

- Aeschlimann FA, Hofer KD, Cannizzaro Schneider E, Schroeder S, Lauener R, Saurenmann RK. Infliximab in Pediatric Rheumatology Patients: A Retrospective Analysis of Infusion Reactions and Cerca con Google

- Alvarado JA, Betanzos A, Franse-Carman L, Chen J, González-Mariscal L. Endothelia of Schlemm's canal and trabecular meshwork: distinct molecular, functional, and anatomic features. Am J Physiol Cell Physiol. 2004 Mar;286(3):C621-34. Epub 2003 Nov 12. Cerca con Google

- Ambati J, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA, Rollins BJ, Ambati BK. An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice. Nat Med. 2003 Nov;9(11):1390-7. Cerca con Google

- Apostolaki M, Armaka M, Victoratos P, Kollias G. Cellular mechanisms of TNF function in models of inflammation and autoimmunity. Curr Dir Autoimmun, 2010;11:1-26. Cerca con Google

- Arend WP. Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist. Semin in Arthritis Rheum, 2001; 30(5 suppl 2): 1-6. Cerca con Google

- Arvin B, Neville LF, Barbone FC, Feurestein CZ. The Role of Inflammation and Cytokines in Brain Injury. Neuroscience & Biobehavioral Reviews. 1996, Vol.20(3):445-452. Cerca con Google

- As R, Fm S, Jp M, Jp CD, Ja Q, Ct T, LA P. Trends in proteomic analysis of human vitreous humor samples. Electrophoresis. 2014 May 13. doi: 10.1002/elps.201400049. Cerca con Google

- Azzolini C, Carta F, Marchini G, Menchini U. Clinica dell'apparato visivo - EdizioniEdra – Masson, 2010; pp. 11-16. Cerca con Google

- Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest. 1998 Aug 15;102(4):783-91. Cerca con Google

- Bischoff P. Macular edema: from symptom to diagnosis. Klin Monbl Augenheilkd. 1999 May;214(5):311-6. Cerca con Google

- Burns SA, Elsner AE, Chui TY, Vannasdale DA Jr, Clark CA, Gast TJ, Malinovsky VE, Phan AD. In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy. Biomed Opt Express. 2014 Feb 27;5(3):961-74. Cerca con Google

- Carroll MC.The complement system in regulation of adaptive immunity. Nat Immunol. 2004 Oct;5(10):981-6. Cerca con Google

- Chen KH, Wu CC, Roy S, Lee SM, Liu JH, Increased Interleukin-in Aqueous Humor Of Neovascular Glaucoma. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2627-32. Cerca con Google

- Chua J, Vania M, Cheung CM, Ang M, Chee SP, Yang H, Li J, Wong TT. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol Vis. 2012;18:431-8. Epub 2012 Feb 11. Cerca con Google

- Contreras-Ruiz L, Ghosh-Mitra A, Shatos MA, Dartt DA, Masli S. Modulation of conjunctival goblet cell function by inflammatory cytokines. Mediators Inflamm. 2013;2013:636812. Cerca con Google

- Dautriche CN, Xie Y, Sharfstein ST. Walking through trabecular meshwork biology: Toward engineering design of outflow physiology. Biotechnol Adv. 2014 May 5. pii: S0734-9750(14)00059-7. Cerca con Google

- David MB, Peter KK, Mark M, et al. Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration. N Engl J Med 2006; 355: 1432–44. Cerca con Google

- Devi TS, Lee I, Huttemann M, Kumar A, Nantwi KD, Singh LP: TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy. Exp Diabetes Res 2012;2012:438238. Cerca con Google

- Dinarello CA. Biologic basis for interleukin-1 in disease. Blood, 1996; 87(6):2095-147. Cerca con Google

- Eisenberg P, Evans J, Arend P, Verderber E, Brewer MT, Hannum H, Thompson C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature, 1990; 343: 341-346. Cerca con Google

- Falcone DJ, McCaffrey TA, Haimovitz-Friedman A, Garcia M.Transforming growth factor-beta1 stimulates macrophage urokinase expression and release of matrix-bound basic fibroblast growth factor. J Cell Physiol. 1993 Jun;155(3):595-605. Cerca con Google

- Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004 Aug;25(4):581-611. Cerca con Google

- Ferris FL III, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR. Clinical classification of age-related macular degeneration. Ophthalmology. 2013; 120: 844–851. Cerca con Google

- Filipe HP, Silva ED, Stulting AA, Golnik KC. Continuing professional development: best practices. Middle East Afr J Ophthalmol. 2014 Apr;21(2):134-41. Cerca con Google

- Firestein GS, Boyle DL, Yu C, Paine MM, Whisenand TD, Zvaifler NJ, et al. Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis. Arthritis Rheum, 1994; 37: 644- 52. Cerca con Google

- Flamme I, Frölich T, Risau W. Molecular mechanisms of vasculogenesis and embryonic angiogenesis. J Cell Physiol. 1997 Nov;173(2):206-10. Cerca con Google

- Folkman J. Fundamental concepts of the angiogenic process. Curr Mol Med. 2003 Nov;3(7):643-51. Cerca con Google

- Friedman DS, Katz J, Bressler NM, Rahmani B, Tielsch JM. Racial differences in the prevalence of age-related macular degeneration: the Baltimore Eye Survey. Ophthalmology. 1999 Jun;106(6):1049-55. Cerca con Google

- Fuchshofer R, Tamm ER. The role of TGF-β in the pathogenesis of primary open-angle glaucoma.Cell Tissue Res. 2012 Jan;347(1):279-90. Cerca con Google

- Fukada T, Hibi M, Yamanaka Y, et al. Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis. Immunity, 1996; 5(5):449-460. Cerca con Google

- Gardlik R, Fusekova I. Pharmacologic Therapy for Diabetic Retinopathy. Semin Ophthalmol. 2014 Feb 27. Cerca con Google

- Goldsby RA, Kindt TJ, Osborne BA. Kuby. Immunologia UTET, 2000. Cerca con Google

- Haspel RL, Salditt-Georgieff M, Darnell JE, Jr. The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase. EMBO J, 1996; 15:6262-6268. Cerca con Google

- Hayes AJ1, Huang WQ, Mallah J, Yang D, Lippman ME, Li LY. Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvasc Res. 1999 Nov; 58(3):224-37. Cerca con Google

- Heinrich PC, Behrmann I, Műller-Newen G, Schaper F, Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J, 1998; 334(Pt 2):297-314. Cerca con Google

- Holz FG, Schmitz-Valckenberg S, Fleckenstein M. Recent developments in the treatment of age-related macular degeneration. J Clin Invest. 2014 Apr 1;124(4):1430-8. Cerca con Google

- Horsley MB & Kahook MI. Anti-VEGF Therapy for Glaucoma.Current Opinion in Ophthalmology. (2010) ; 21 :112-117. Cerca con Google

- Iancu R, Corbu C. Intraocular pressure after phacoemulsification in patients with uncontrolled primary open angle glaucoma. J Med Life. 2014 Mar 15;7(1):11-6. Cerca con Google

- Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y, Khan S, Al-Gayyar MM. El-Shishtawy MM, Liou GI. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes2001, 60: 1122-1133. Cerca con Google

- Ihle JN. The Janus kinase family and signaling through members of the cytokine receptor superfamily. Proc Soc Exp Biol Med, 1994; 206(3):268-272. Cerca con Google

- Ishida S, Usui T, Yamashiro K, et al. VEGF164 – mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascolarization. J Exp Med. 2003;198:483-89 Cerca con Google

- Izzotti A, Longobardi M, Cartiglia C, Saccà SC. Proteome alterations in primary open angle glaucoma aqueous humor. J Proteome Res. 2010 Sep 3;9(9):4831-8. Cerca con Google

- Jacobs M, Samarina A, Grivennikov S, et al. Reactivation of tuberculosis by tumor necrosis factor neutralization. Eur Cytokine Netw, 2007;18(1):5-13. Cerca con Google

- Jonasson F, Fisher DE, Eiriksdottir G, Sigurdsson S, Klein R, Launer LJ, Harris T, Gudnason V, Cotch MF. Five-Year Incidence, Progression, and Risk Factors for Age-related Macular Degeneration: The Age, Gene/Environment Susceptibility Study. Ophthalmology. 2014 Apr 23. Cerca con Google

- Joussen AM, Doehmen S, Le ML, Koizumi K, Radetzky S, Krohne TU, Poulaki V, Semkova I, Kociok N: TNF-α mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Molecular vision 2009;15:1418. Cerca con Google

- Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G. Transgenic mice expressing human tumor necrosis factor: a predictive genetic model of arthritis. EMBO J, 1991; 10(13):4025-4031. Cerca con Google

- Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G. Impaired on/off regulaton of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity, 1999;10(3):387-398. Cerca con Google

- Krause TA, Alex AF, Engel DR, Kurts C, Eter N. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization. PLoS One. 2014 Apr 8;9(4):e94313. Cerca con Google

- Kriegler M, Perez C, DeFay K, Albert I, Lu SD. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell, 1988; 53:45-53. Cerca con Google

- Kwon YH, Fingert JH, Kuehn MH, Alward WL. Primary open-angle glaucoma. N Engl J Med 2009; 360:1113–1124 Cerca con Google

- Labbé A,Gabison E, Brignole-Baudouin F, Riancho L, Menashi S, Baudouin C. Increased Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Expression in the Conjunctival Epithelium Exposed to Antiglaucoma Treatments. Curr Eye Res. 2014 May 15:1-8 Cerca con Google

- Langmann T: Microglia activation in retinal degeneration. J Leukoc Biol 2007;81:1345-1351. Cerca con Google

- Liou GI: Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation. World J Diabetes 2010;1:12-18. Cerca con Google

- Liu W, Xu GZ, Jiang CH, Tian J: Macrophage colony-stimulating factor and its receptor signaling augment glycated albumin-induced retinal microglial inflammation in vitro. BMC Cell Biol 2011;12:5. Cerca con Google

- Liu Y, Biarnes Costa M, Gerhardinger C: IL-1beta is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1beta autostimulation. PLoS One 2012;7:e36949. Cerca con Google

- Lotz M. Interleukin-6: a comprehensive review. Cancer Treat.Res, 1995; 80:209-233. Cerca con Google

- Lou J, Lucas R, Grau GE. Pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. Clin Microbiol Rev, 2001;14(4):810-820. Cerca con Google

- Montero-Julian FA. The soluble IL-6 receptors: serum levels and biological function. Cell Mol Biol, 2001; 47(4):583-597. Cerca con Google

- Mullins RF, Khanna A, Schoo DP, Tucker BA, Sohn EH, Drack AV, Stone EM. Is age-related macular degeneration a microvascular disease? Adv Exp Med Biol. 2014;801:283-9. Cerca con Google

- Munemasa Y, Kitaoka Y. Molecular mechanisms of retinal ganglion cell degeneration in glaucoma and future prospects for cell body and axonal protection. Front Cell Neurosci. 2013 Jan 9;6:60. Cerca con Google

- Naka T, Nishimoto N, Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthritis Res, 2001; 4 Suppl 3:S233-S242. Cerca con Google

- Naka T, Nishimoto N, Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthritis Res, 2001; 4 Suppl 3:S233-S242. Cerca con Google

- Nguyen QD, Shah SM, Browning DJ, Hudson H, Sonkin P, Hariprasad SM, Kaiser P, Slakter JS, Haller J, Do DV, Mieler WF, Chu K, Yang K, Ingerman A, Vitti RL, Berliner AJ, Cedarbaum JM, Campochiaro PA. A phase I study of intravitreal vascular endothelial growth factor trap-eye in patients with neovascular age-related macular degeneration. Ophthalmology 2009 Nov;116(11):2141-8. Cerca con Google

- Ohtani T, Ishihara K, Atsumi T, et al. Dissection of signaling cascades through gp130 in vivo: reciprocal roles for STAT3- and SHP-mediated signals in immune responses. Immunity, 2000; 12(1):95-105. Cerca con Google

- Owen LA, Hartnett ME. Soluble mediators of diabetic macular edema: the diagnostic role of aqueous VEGF and cytokine levels in diabetic macular edema. Curr Diab Rep. 2013 Aug;13(4):476-80. Cerca con Google

- Paloma B Liton, Guorong Li, Coralia Luna, Pedro Gonzalez, David L Epstei.Cross-talk between TGF-beta1 and IL-6 in human trabecular meshwork cells. Molecular vision 02/2009; 15:326-34. Cerca con Google

- Pasparakis M, Alexopoulu L, Espiskopou V, Kollias G. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med 1996;184(4):1397-1411. Cerca con Google

- Pasparakis M, Kousteni S, Peschon J, Kollias G. Tumor necrosis factor and the p55TNF receptor are required for optimal development of the marginal sinus and for migration of follicular dendritic cell precurors into splenic follicles. Cell Immunol, 2000; 201:33-41. Cerca con Google

- Pfeffer K, Matsuyama T, Kűndig TM, et al. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell, 1993; 73(3):457-467. Cerca con Google

- Pflugfelder SC, Corrales RM, de Paiva CS. T helper cytokines in dry eye disease. Exp Eye Res. 2013 Dec;117:118-25. Cerca con Google

- Pontieri G M, Russo M A, Frati L. Patologia generale. Piccin, 2010; pp.355-362. Cerca con Google

- Prendes MA, Harris A, Wirostko BM, Gerber AL, Siesky B.The role of transforming growth factor β in glaucoma and the therapeutic implications. Br J Ophthalmol. 2013 Jun;97(6):680-6. Cerca con Google

- Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system- specific expression of tumor necrosis factor alpha. Proc Natl Acad Sci USA, 1995; 92:11294- 11298. Cerca con Google

- Rangasamy S, McGuire PG, Das A: Diabetic retinopathy and inflammation:Novel therapeutic targets. Middle East African Journal of Ophthalmology 2012;19:52. Cerca con Google

- Rangasamy S, McGuire PG, Das A: Diabetic retinopathy and inflammation: Novel therapeutic targets. Middle East African Journal of Ophthalmology 2012;19:52. Cerca con Google

- Resnikoff S1, Pascolini D, Mariotti SP, Pokharel GP. Global magnitude of visual impairment caused by uncorrected refractive errors in 2004. Bull World Health Organ. 2008 Jan;86(1):63-70. Cerca con Google

- Robbins SL, Kumar V, Abbas AK, Cotran RS, Fausto N. “Robbins and Cotran pathologic basis of disease”, 2010; Milano: Elsevier. Cerca con Google

- Roh M, Zhang Y, Murakami Y, Thanos A, Lee SC, Vavvas DG, Benowitz LI, Miller JW, Etanercept, a Widely Used Inhibitor of Tumor Necrosis Factor-α (TNF-α), Prevents Retinal Ganglion Cell Lös a Rat Model of Glaucoma, PloS ONE, (2012); 7(7) :e40065. Cerca con Google

- Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355: 1419–31. Cerca con Google

- Rothe J, Lesslauer W, Lotscher H, et al. Mice lacking the tumor necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature, 1993; 364:798-802. Cerca con Google

- Rungger–Brändle E, Dosso AA, Leuenberger PM: Glial reactivity, an early feature of diabetic retinopathy. Invest Ophthalmol Vis Sci 2000;41:1971-1980. Cerca con Google

- Russo RA, Brogan PA.Monogenic autoinflammatory diseases. Rheumatology (Oxford). 2014 May 15. pii: keu170. Cerca con Google

- Sappington RM, Calkins DJ. Pressure-induced regulation of IL-6 in retinal glial cells: involvement of the ubiquitin/proteasome pathway and NFkappaB. Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3860-9. Cerca con Google

- Shelton MD, Distler AM, Kern TS, Mieyal JJ: Glutaredoxin regulates autocrine and paracrine proinflammatory responses in retinal glial (muller) cells. J Biol Chem 2009;284:4760-4766. Cerca con Google

- Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, Hofman A, Jensen S, Wang JJ, de Jong PT. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001 Apr;108(4):697-704. Cerca con Google

- Sonne O, Davidsen O, Moller BK, Munck PC. Cellular targets and receptors for interleukin-6. I. In vivo and in vitro uptake of IL-6 in liver and hepatocytes. Eur J Clin Invest, 1990; 20(4):366-376. Cerca con Google

- Stahl N, Farruggella TJ, Boulton TG, Zhong Z, Darnell JE Jr., Yancopoulos GD. Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science, 1995; 267:1349-1353. Cerca con Google

- Stanton CM, Wright AF. Inflammatory Biomarkers for AMD. Adv Exp Med Biol. 2014;801:251-7. Cerca con Google

- Starr R, Willson TA, Viney EM, et al. A family of cytokine-inducible inhibitors of signalling. Nature, 1997; 387(6636):917- 921. Cerca con Google

- Takeuchi K, Nakazawa M, Ebina Y, Effects of Trehalose on VEGF-Stimulated Angiogenesis and Myofibroblast Proliferation: Implications for Glaucoma Filtration Surgery, Physiology and Pharmacology, (2011); Vol.52, No.9. Cerca con Google

- Tamm ER, Toris CB, Crowston JG, Sit A, Lim S, Lambrou G, Alm A. Basic science of intraocular pressure. Edited by Weinreb RN, Brandt JD, Garway-Heath D, Medeiros F. Amsterdam. Kugler Publications, 2007; p. 1–14. Cerca con Google

- Tang J, Kern TS: Inflammation in diabetic retinopathy. Prog Retin Eye Res 2011;30:343-358. Cerca con Google

- Uva MG, Longo A, Reibaldi M. Pneumatic trabeculoplasty versus argon laser trabeculoplasty in primary open-angle glaucoma. Ophthalmologica. 2010;224(1):10-5. Cerca con Google

- Vandenabeele P, Declerq W, Bayaert R, Fiers W. Two tumor necrosis factor receptors: structure and function. Trend Cell Biol, 1995; 5(10):392-399. Cerca con Google

- Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol, 1992; 10:411-452. Cerca con Google

- Vinay DS, Kwon BS. TNF superfamily: costimulation and clinical applications. Cell Biol Int, 2009; 33(4):453-465. Cerca con Google

- Vlantis K, Pasparakis M. Role of TNF in pathologies induced by nuclear factor kappaB deficiency. Curr Dir Autoimmunity, 2010; 11:80-93. Cerca con Google

- Wang AL, Li Z, Yuan M, Yu AC, Zhu X, Tso MO. Sinomenine inhibits activation of rat retinal microglia induced by advanced glycation end products. Int Immunopharmacol. 2007 Dec 5;7(12):1552-8. Cerca con Google

- Wegenka UM, Buschmann J, Lutticken C, Heinrich PC, Horn F. Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level. Mol Cell Biol, 1993; 13(1):276-288. Cerca con Google

- Xu YX, Chen L, Hou WK, Lin P, Sun L, Sun Y, Dong QY, Liu JB, Fu YL.Mesenchymal stem cells treated with rat pancreatic ext ract secrete cytokines that improve the glycometabolism of diabetic rats. Transplant Proc. 2009 Jun;41(5):1878-84. Cerca con Google

- Yoshizaki K, Nishimoto N, Mihara M, Kishimoto T. Therapy of rheumatoid arthritis by blocking IL-6 signal transduction with a humanized anti-IL-6 receptor antibody. Springer Semin Immunopathol, 1998; 20(1-2):247-259. Cerca con Google

- Zeng HY, Green WR, Tso MO: Microglial activation in human diabetic retinopathy. Arch Ophthalmol 2008;126:227-232. Cerca con Google

- Zeng J, Chen B. Epigenetic Mechanisms in the Pathogenesis of Diabetic Retinopathy. Ophthalmologica. 2014 Apr 4. Cerca con Google

- Zong H, Ward M, Madden A, Yong P, Limb G, Curtis T, Stitt A: Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE). Diabetologia 2010;53:2656-2666. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record