Intraocular Cytokine Environment in Active Behçet Uveitis

Ahn, Jae-Min; Yu, Hyeong Gon; Chung, Hum; Park, Yeoung Geol

doi:10.1016/j.ajo.2006.04.016

Cited by 128 publications

(83 citation statements)

References 26 publications

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“…2 In patients with uveitis, high levels of TNF-a have been found in the ocular media. 3,4 Furthermore, polymorphisms within the TNF-a promoter region and the TNF-a receptors genes have been associated with a significant increased susceptibility for developing intraocular inflammation in HLA-B27 + patients. 5,6 Based on these initial findings, pilot studies have demonstrated the efficacy of anti-TNFa strategies for the treatment of refractory uveitis using either etanercept (a p75 TNF receptor fusion protein), infliximab (a chimeric immunoglobulin G (IgG) monoclonal antibody (mAb) directed against TNF-a) or adalimumab (a human monoclonal TNF-a antibody).…”

Section: Introductionmentioning

confidence: 99%

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

et al. 2009

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Intraocular inflammation has been recognized as a major factor leading to blindness. Because tumor necrosis factor-a (TNF-a) enhances intraocular cytotoxic events, systemic anti-TNF therapies have been introduced in the treatment of severe intraocular inflammation, but frequent re-injections are needed and are associated with severe side effects. We have devised a local intraocular nonviral gene therapy to deliver effective and sustained anti-TNF therapy in inflamed eyes. In this study, we show that transfection of the ciliary muscle by plasmids encoding for three different variants of the p55 TNF-a soluble receptor, using electrotransfer, resulted in sustained intraocular secretion of the encoded proteins, without any detection in the serum. In the eye, even the shorter monomeric variant resulted in efficient neutralization of TNF-a in a rat experimental model of endotoxininduced uveitis, as long as 3 months after transfection. A subsequent downregulation of interleukin (IL)-6 and iNOS and upregulation of IL-10 expression was observed together with a decreased rolling of inflammatory cells in anterior segment vessels and reduced infiltration within the ocular tissues. Our results indicate that using a nonviral gene therapy strategy, the local self-production of monomeric TNF-a soluble receptors induces a local immunomodulation enabling the control of intraocular inflammation.

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Section: Introductionmentioning

confidence: 99%

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

et al. 2009

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“…7,8 TNFA-1031*2 occurs in a TNFA haplotype associated with Behcet's disease, 28 a condition associated with local increases in TNF-␣. 29 Further, alleles at several loci upstream of TNFA (including TNFA-1031) associate with poor control of HIV viremia 30 and with HIV-associated lipodystrophy. 31 Therefore, the association between TNFA-1031*2 and NRTI-SN following dNRTI exposure is biologically plausible and consistent with findings from other disease states.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Genotype Suggests a Role for Inflammation in Nucleoside Analog-Associated Sensory Neuropathy (NRTI-SN) and Predicts an Individual's NRTI-SN Risk

Cherry

Rosenow

Affandi

et al. 2008

AIDS Research and Human Retroviruses

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Nucleoside analog-associated sensory neuropathy (NRTI-SN) attributed to stavudine, didanosine, or zalcitabine (the dNRTIs) and distal sensory polyneuropathy (DSP) attributed to HIV are clinically indistinguishable. As inflammatory cytokines are involved in DSP, we addressed a role for inflammation in NRTI-SN by determining the alleles of immune-related genes carried by patients with and without NRTI-SN. Demographic details associated with risk of various neuropathies were included in the analysis. Alleles of 14 polymorphisms in 10 genes were determined in Australian HIV patients with definite NRTI-SN (symptom onset Ͻ6 months after first dNRTI exposure, n ‫؍‬ 16), NRTI-SN-resistant patients (no neuropathy despite Ͼ6 months on dNRTIs, n ‫؍‬ 20), patients with late onset NRTI-SN (neuropathy onset after Ͼ6 months of dNRTIs, n ‫؍‬ 19), and HIV-negative controls. Carriage of TNFA-1031*2 was highest in NRTI-SN patients, suggesting potentiation of NRTI-SN. Carriage of IL12B (3Ј UTR)*2 was higher in NRTI-SN-resistant patients than controls or NRTI-SN patients, suggesting a protective role. BAT1 (intron 10)*2 was more common in NRTI-SN than resistant patients, but neither group differed from controls. This marks the conserved HLA-A1, B8, DR3 haplotype. Of the demographic details considered, increasing height was associated with NRTI-SN risk. A model including cytokine genotype and height predicted NRTI-SN status (p Ͻ 0.0001, R 2 ‫؍‬ 0.54). Late onset NRTI-SN patients clustered genetically with NRTI-SN-resistant patients, so these patients may be genetically "protected." In addition to patient height, cytokine genotype influenced NRTI-SN risk following dNRTI exposure, suggesting inflammation contributes to NRTI-SN. 117

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“…This immuno-inflammatory response may cause tissue damage in the conjunctiva and the cornea of the BD patients. [16][17][18] In a previous study, the mean flare of anterior chamber of BD patients without active inflammation were evaluated and the mean flare in these eyes that were in remission were found to be significantly higher. 19 Based on this study, we designed our research, in order to identify what type of changes could happen in the eyes of BD patients without active inflammation.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Tear Film Function and Corneal Thickness of Behcet's Disease Patients Without Ocular Involvement

Karci¹,

Aslan²,

Güler³

et al. 2017

Turkiye Klinikleri J Ophthalmol

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A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Behcet's disease (BD) is a chronic inflammatory vasculitis characterized by mucocutaneous ulcers and ocular involvement. There are a few studies about the effects of BD on the ocular surface. We aimed to investigate central corneal thickness (CCT) and tear film function in patients without clinically detectable ocular pathology. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Eighty nine eyes of 45 BD patients without ocular pathology were examined and compared with 52 eyes of 26 healthy, age and sex matched volunteers. For both groups, after routine opthalmologic examinations, tear film function tests, containing tear break-up time (BUT) and Schirmer test were done. CCT was measured with ultrasonic pachymeter. Schirmer test results, CCT and BUT measurements were compared and p<0,05 was considered statistically significant. R Re es su ul lt ts s: : Mean values of Schirmer tests in patient and control groups were 7.62±5.87 mm and 9.32±3.92 mm, respectively. Difference between groups was not statistically significant (p= 0.06). Mean BUT was significantly lower in the patient group (p= 0.0001). Mean CCT of patient and control groups were 536.13±31.47 μm and 540,90±36,39 μm, respectively. There was no significant difference between the CCT of the groups (p= 0.41). All parameters were similar for patients receiving and not receiving immunosuppressive therapy (p>0.05). C Co on nc cl lu us si io on n: : There may be changes in tear film functions of BD patients without clinically detectable ocular pathology. Since BUT test results were found to be significantly lower in our patient group we concluded that BD patients without ocular pathology must also be evaluated for symptoms of dry eye. K Ke ey yw wo or rd ds s: : Behcet syndrome; cornea; dry eye syndromes Ö ÖZ ZE ET T A Am ma aç ç: : Behçet Hastalığı (BH) mukokutanöz ülserler ve oküler tutulum ile karakterize kronik inflamatuar bir vaskülittir. Behçet hastalığının oküler yüzey üzerine etkisini bildiren çok az çalışma vardır. Klinik olarak oküler bulguları olmayan Behçet hastalarının gözyaşı fonksiyonlarını ve kornea kalınlıklarını değerlendirmeyi amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Oküler patolojisi olmayan 45 Behçet hastasının 89 gözü, benzer yaş ve cinsiyette 26 sağlıklı gönüllü bireyin 52 gözü incelendi ve karşılaştırıldı. Her iki gruba rutin oftalmolojik muayeneyi takiben göz yaşı kırılma zamanı (GKZ) ve Schirmer testi içeren göz yaşı fonksiyon testleri yapıldı. Santral kornea kalınlığı (SKK) ultrasonografik pakimetri ile ölçüldü. Grupların Schimer test sonuçları, GKZ ve SKK değerleri istatistiksel analizler ile karşılaştırıldı, p< 0,05 istatistiksel olarak anlamlı kabul edildi. B Bu ul lg gu ul la ar r: : Hasta ve kontrol grubunun ortalama Schirmer test değerleri sırasıyla 7,62±5,87 mm ve 9,32±3,92 mm olarak ölçüldü. Gözyaşı fonksiyon değerlendirilmesinde Schirmer testi sonuçları her iki grup için benzerdi (p= 0,06). Göz yaşı kırılma zamanı (GKZ) kontrol grubunda a...

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Intraocular Cytokine Environment in Active Behçet Uveitis

Cited by 128 publications

References 26 publications

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

Cytokine Genotype Suggests a Role for Inflammation in Nucleoside Analog-Associated Sensory Neuropathy (NRTI-SN) and Predicts an Individual's NRTI-SN Risk

Evaluation of Tear Film Function and Corneal Thickness of Behcet's Disease Patients Without Ocular Involvement

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