The TNF-α level variation in the aqueous humour of the anterior chamber inindividuals with cataract

Author(s):  
V.S. Shevchenko ◽  
◽  
A.S. Prilutskii ◽  
K.Y. Tkachenko ◽  
◽  
...  

Актуальность. Фактор некроза опухоли(TNF-α) является провоспалительным цитокином, продуцирующимся макрофагами и многими другими клетками. Данные о вариации концентрацииTNF-α во влаге передней камеры глаза у лиц, не имеющих выраженных воспалительных и аутоиммунных процессов практически единичны. Цель. Исследование диапазона вариации фактора некроза опухоли альфа во влаге передней камеры глаза у пациентов с возрастной катарактой. Материал и методы. Отобраны и обследованы 33 пациента, в возрасте от 47 до 82 лет, госпитализированных для плановой экстракции катаракты не имеющих выраженных сопутствующих воспалительных заболеваний (аутоиммунных, острых инфекционных болезней, обострением хронических заболеваний, глаукомы, перенесенного увеита и др.). Влага передней камеры забиралась при вскрытии передней камеры глаза во время факоэмульсификации катаракты. Исследование TNF-αпроводилось с помощью иммуноферментны хтест-систем, разработанных при участии сотрудников кафедры клинической иммунологии, аллергологии и эндокринологии ГОО ВПО «ДонНМУ им.М. Горького». Вышеуказанные тест-системы характеризует высокая чувствительность (0,5 пикограмм в миллилитре) и хорошая воспроизводимость. Результаты. При исследовании уровня TNF-αво влаге передней камеры глаза у пациентов с возрастной катарактой, мы выявили колебания данного показателя от 0 до 2,49 пкг/мл. Следует отметить, что полученные нами результаты показывают небольшую вариацию (в пределах низких значений) данного провоспалительного цитокина в исследованной жидкости у пациентов в возрасте от 47 до80 лет, не имеющих выраженной воспалительной(аутоиммунной и др.) патологии. Выводы. Показана низкая вариация TNF-α во влаге передней камеры глаза у пациентов с возрастной катарактой (у обследуемых исключена сопутствующая выраженная воспалительная патология). Результаты можно также использовать как контрольные при проведении сравнительныхисследований этого цитокина в данной среде у лицс различными заболеваниями глаза.

Author(s):  
V.S. Shevchenko ◽  
◽  
A.S. Prilutskii ◽  
K.Y. Tkachenko ◽  
◽  
...  

Актуальность. TNF-α является провоспалительным цитокином, имеющим широкий спектр патофизиологических эффектов. В норме, в кровиTNF-α находится в минимальных концентрациях, однако при воспалительных (аутоиммунных и др.)процессах резко возрастает. Вместе с тем данные об изменениях уровня TNF-α во влаге передней камеры глаза при различных заболеваниях немногочисленны. Практически единичны они при возрастной катаракте. При этом исследования концентрации данного цитокина у лиц с вышеуказанной патологией в зависимости от наличия сопутствующей гипертонической болезни (ГБ) отсутствуют. Следует отметить, что TNF-α участвует в патогенезе ГБ и концентрация его в крови может иметь корреляцию со степенью её. Цель. Изучение уровня TNF-α во влаге передней камеры глаза у пациентов с возрастной катарактой в зависимости от наличия ГБ. Материал и методы. Из 68 пациентов с возрастной катарактой был отобран 21 пациент с отсутствием сопутствующих выраженных аутоиммунных и воспалительных заболеваний. Кроме того, у выбранных больных в анамнезе отсутствовали прочие заболевания глаз (увеит, глаукома и др.). Пациенты были госпитализированы для планового оперативного лечения по поводу катаракты. У 11 из данных лиц гипертоническая болезнь отсутствовала. 2-я стадия ГБ была диагностирована у10 пациентов. Влага передней камеры глаза для исследования забиралась у пациентов во время факоэмульсификации катаракты. Исследование TNF-αпроводилось с помощью разработанных нами иммуноферментных тест-систем. Результаты. Результаты исследований показали, что уровень фактора некроза опухоли-альфа во влаге передней камеры глаза у пациентов со 2стадией ГБ был существенно выше (p=0,025), чему пациентов с катарактой без данной сопутствующей патологии. Выводы. Показано достоверное увеличение концентрации TNF-α у лиц с катарактой в сочетании со 2 стадией гипертонической болезни. Полученные данные следует учитывать, как при проведении лечебной работы так и при осуществлении научных исследований.


2019 ◽  
Vol 98 (12) ◽  
pp. 1386-1396 ◽  
Author(s):  
X. Hong ◽  
S.N. Min ◽  
Y.Y. Zhang ◽  
Y.T. Lin ◽  
F. Wang ◽  
...  

IgG4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic fibroinflammatory disease that affects salivary glands and leads to hyposalivation. Tumor necrosis factor–α (TNF-α) is a critical proinflammatory cytokine involved in several salivary gland disorders, but its role and mechanism regarding acinar cell injury in IgG4-RS are unknown. Here, we found that TNF-α level was significantly increased in serum and submandibular gland (SMG) of patients and that serum TNF-α level was negatively correlated with saliva flow rate. Ultrastructural observations of IgG4-RS SMGs revealed accumulation of large autophagic vacuoles, as well as dense fibrous bundles, decreased secretory granules, widened intercellular spaces, swollen mitochondria, and expanded endoplasmic reticulum. Expression levels of LC3 and p62 were both increased in patients’ SMGs. TNF-α treatment led to elevated levels of LC3II and p62 in both SMG-C6 cells and cultured human SMG tissues but did not further increase their levels when combined with bafilomycin A1 treatment. Moreover, transfection of Ad-mCherry-GFP-LC3B in SMG-C6 cells confirmed the suppression of autophagic flux after TNF-α treatment. Immunofluorescence imaging revealed that costaining of LC3 and the lysosomal marker LAMP2 was significantly decreased in patients, TNF-α–treated SMG-C6 cells, and cultured human SMGs, indicating a reduction in autophagosome-lysosome fusion. Furthermore, the ratio of pro/mature cathepsin D was elevated in vivo, ex vivo, and in vitro. TNF-α also appeared to induce abnormal acidification of lysosomes in acinar cells, as assessed by lysosomal pH and LysoTracker DND-26 fluorescence intensity. In addition, TNF-α treatment induced transcription factor EB (TFEB) redistribution in SMG-C6 cells, which was consistent with the changes observed in IgG4-RS patients. TNF-α increased the phosphorylation of extracellular signal–regulated kinase (ERK) 1/2, and inhibition of ERK1/2 by U0126 reversed TNF-α–induced TFEB redistribution, lysosomal dysfunction, and autophagic flux suppression. These findings suggest that TNF-α is a key cytokine related to acinar cell injury in IgG4-RS through ERK1/2-mediated autophagic flux suppression.


Eye ◽  
2021 ◽  
Author(s):  
Inês C. F. Pereira ◽  
Rosanne van de Wijdeven ◽  
Hans M. Wyss ◽  
Henny J. M. Beckers ◽  
Jaap M. J. den Toonder

AbstractGlaucoma is a progressive optic neuropathy that is the second leading cause of preventable blindness worldwide, after cataract formation. A rise in the intraocular pressure (IOP) is considered to be a major risk factor for glaucoma and is associated with an abnormal increase of resistance to aqueous humour outflow from the anterior chamber. Glaucoma drainage devices have been developed to provide an alternative pathway through which aqueous humour can effectively exit the anterior chamber, thereby reducing IOP. These devices include the traditional aqueous shunts with tube-plate design, as well as more recent implants, such as the trabeculectomy-modifying EX-PRESS® implant and the new minimally invasive glaucoma surgery (MIGS) devices. In this review, we will describe each implant in detail, focusing on their efficacy in reducing IOP and safety profile. Additionally, a critical and evidence-based comparison between these implants will be provided. Finally, we will propose potential developments that may help to improve the performance of current devices.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.


2017 ◽  
Vol 12 (1) ◽  
pp. 35 ◽  
Author(s):  
Dian Ratih Laksmitawati ◽  
Anisa Widyastuti ◽  
Nadia Karami ◽  
Ervi Afifah ◽  
Dwi Davidson Rihibiha ◽  
...  

<p class="Abstract">In this study, the anti-inflammatory potential of <em>Anredera </em>cordifolia and <em>Piper </em>crocatum extracts on lipopolysaccharide-induced murine macrophage cell line (RAW 264.7) was observed. Cell viability assay was performed with MTS assay. Parameters measured to determine the anti-inflammatory activity were interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, nitric oxide (NO) and IL-6. Both <em>A. </em>cordifolia and<em> P. </em>crocatum at concentration of 50 µg/mL in cell line resulted significant decrease in TNF-α level (250.3 and 242.5 pg/mL respectively). <em>A. </em>cordifolia showed significant decrease in IL-1β level at 50 µg/mL and IL-6 level at 10 µg/mL, whilst <em>P. </em>crocatum  showed significant decrease IL-1β level in three concentrations with lowest level at 50 µg/mL.<em> A. </em>cordifolia showed lowest decrease in NO level at 50 µg/mL but not comparable with normal cells, whilst <em>P. </em>crocatum showed significant decrease in NO level at 50 µg/mL. This research revealed that <em>A. </em>cordifolia and<em> P. </em>crocatum possess the anti-inflammatory potential indicated by the inhibitory activity of the inflammatory mediators including, TNF-α, IL-1β, IL-6, and NO.</p>


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Annabel C. Y. Chew ◽  
Li-Fong Seet ◽  
Stephanie W. L. Chu ◽  
Nyein C. Lwin ◽  
Tina T. Wong

Abstract Background Peripheral iridectomy (PI), routinely performed during glaucoma filtration surgery, may contribute to scarring. This study aims to determine whether PI alters the concentrations of VEGF-A and TGF-β isoforms in the rabbit aqueous humour. Methods Anterior chamber paracentesis (ACP) was performed in both eyes of six New Zealand white rabbits, with additional surgical PI performed in the right eyes. Eyes were examined on postoperative days (PODs) 1, 7, 30 and 60 by means of the tonopen, slit-lamp biomicroscopy, and bead-based cytokine assays for TGF-β and VEGF-A concentrations in the aqueous humor. Results ACP caused a significant reduction in intraocular pressure (IOP) from mean preoperative 11.47 ± 1.01 mmHg to 5.67 ± 1.63 mmHg on POD 1 while PI did not cause further IOP reduction. Limbal conjunctival vasculature appeared slightly increased on POD 1 in both ACP and PI eyes with PI also causing mild bleeding from damaged iris vessels. Two PI eyes developed fibrinous anterior chamber reaction and/ or peripheral anterior synechiae. Aqueous VEGF-A levels were not significantly different between eyes treated with ACP and PI. Aqueous TGF-β concentrations distributed in the ratio of 4:800:1 for TGF-β1:TGF-β2:TGF-β3 respectively. While aqueous TGF-β2 was not significantly induced by either procedure at any time point, TGF-β1 and TGF-β3 were significantly induced above baseline levels by PI on POD 1. Conclusion PI increases the risk of inflammation. The combined induction of aqueous TGF-β1 and TGF-β3 by PI in glaucoma surgery may impact surgery success in glaucoma subtypes sensitive to these isoforms.


Author(s):  
Svetlana Čapenko ◽  
Marija Mihailova ◽  
Santa Rasa ◽  
Angelika Krūmiņa ◽  
Zane Zazerska ◽  
...  

Abstract Fibromyalgia (FM) is a chronic widespread pain disorder that impacts 0.5%-7% of the general population worldwide. The aetiology and pathogenesis of the disease are still unknown. Human herpesvirus-6 and -7 belong to the family Herpesviridae, subfamily Betaherpesvirinae, and genus Roseolovirus and are immunomodulating viruses potentially pathogenic to the nervous system. Presence of anti-HHV-6 and -HHV-7 antibodies and viral genomic sequences, viral loads, HHV-6 variant-specificity, and TNF-α level were studied in 41 FM patients and 50 healthy individuals using polymerase chain reactions, restriction endonuclease analysis and ELISA. There was no difference in the presence of anti-HHV-6 and anti-HHV-7 IgG class antibodies between FM patients and control group individuals. Viral sequences were found in 80.5% of FM patients and in 62.0% of controls. Significantly higher rate of concurrent HHV-6 and HHV-7 infection and higher viral loads in peripheral blood were detected in FM patients compared to the control group individuals. Plasma viremia was detected only in FM patients. Significantly higher TNF-α levels were detected in virus positive FM patients. From all positive cases only in two FM patients HHV-6A was revealed. Significantly higher detection frequency of concurrent HHV-6 and HHV-7 infection, simultaneous HHV-6 and HHV-7 activation, higher viral loads and TNF-α expression levels in primary FM patients than in control group individuals indicate the potential involvement of Roseoloviruses in development of this disorder.


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