Objective
To observe the expression of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor of matrix metalloproteinase (TIMP-1), inducible nitric oxide synthase (iNOS) and contents of nitric oxide (NO) in the ocular tissues of Sprague-Dawley (SD) rats with endotoxin induced uveitis（EIU）.
Methods
Ninety SD rats were randomly divided into experimental (81 rats) and control group (9 rats). The model of EIU was induced in rats in experimental group by injecting with lipoplysaccharide (LPS) 200 μl into the hind feet pads, while the rats in the control group were not injected. Nine rats were executed 0, 6, 12, 18, 24, 48, 72, 96 hours and 7 days, respectively, after injecting with LPS; the NO content and concentration of protein in the aqueous humor in blood plasma, aqueous humor, and uveal tissues were detected. The expressions of MMP-9, TIMP-1 and iNOS in the ocular tissues were detected by immunohistochemistry, and the average absorbance (A) value was evaluated by computer medical image analysis system.
Results
iNOS, MMP-9 and TIMP-1 expressed in the epithelial cells of iris and ciliary body and exudated inflammatory cells of rats. The concentration of protein in the aqueous humor, the contents of NO in blood plasma, aqueous humor, and uveal tissues, and A value of MMP-9 had obvious relativity with the inflammatory extent, while no positive correlation was found between the inflammatory extent and the A value of iNOS and TIMP-1. Expression of iNOS was found 6 hours after injection, reached the peak after 12 hours, and then dropped gradually. The expression of TIMP-1 could be seen 24 hours after injection, and reached its peak after 72 hours.
Conclusion
The content of NO and expressions of iNOS, MMP-9 and TIMP-1 changes from the beginning and during the development of EIU, which suggests that NO, iNOS, MMP-9 and TIMP-1 are involved in the pathologic process of EIU.
(Chin J Ocul Fundus Dis, 2005, 21: 371-374)
Objective To observe the therapeutic effect of mensenchymal stem cells (MSCs) for experimental autoimmune uveitis (EAU). Methods MSCs were obtained from Wistar rats and selected by plastic adherence. Lewis rats were divided into treatment group and control group, six rats in each group. EAU models were induced by immunization with an emulsion (0.2 ml) containing 30 mu;g interphotoreceptor retinoid-binding protein derived peptide R16 and complete Freundprime;s adjuvant. The clinical manifestations of two groups were observed. Nine to 11 day after modeling, 1 ml MSCs suspension, which contained 5times;106 MSCs, were injected into the rats in treatment group via tail vein, and the rats in control group were given equal volume of phosphate buffer solution. Fifteen day after modeling, the eyes were collected to test the proportion of interferon gamma;, interleukin-17 and Foxp3 positive cells by flow cytometry. The clinical scores were analyzed by mixed linear model and statistical analysis of variance of repeated measurement data. The results of flow cytometry were analyzed using independent-sample t test. Results Six days after immunization, mild dilatation and congestion of iris vascular was observed. Nine days after immunization, mild muddy anterior chamber, myosis and absent pupillary reaction to light were observed. Twelve days after immunization, muddy anterior chamber, occlusion of pupil and dimmed or disappeared red reflex were observed, and then inflammation was slowly reduced. From 11 to 15 days after immunization, the clinical score of treatment group was lower than that in control group, the difference was statistically significant (t=2.42, 2.21, 4.16, 5.24, 4.03; P＜0.05). The results of flow cytometry showed that MSCs treatment could decrease the proportion of CD4＋T cells, Th1 cells and Th17 cells, increase the proportion of Treg cells. Conclusion MSCs treatment can ameliorate EAU, up-regulate the expression of Treg cells and down-regulate the expression of CD4＋T cells, Th1 cells and Th17 cells.
Objective To observe the proportion changes of CD4+CD25+FOXP3+ T cells in peripheral blood of patients with VogtKoyanagiHarada disease (VKH) before and after one month of treatment. Methods he peripheral blood samples from 15 patients with VKH disease before and after one month of treatment by glucocorticoid, and from 15 healthy volunteers were collected，and lymphocytes were separated from them. CD4+CD25+ regulatory T cells were labeled by antibodies of cell surface marker CD4、CD25 and transcription factor FOXP3. The proportion of CD4+CD25+FOXP3+ T cells were detected by flow cytometry. Results Before the treatment, the percentage of CD4+CD25+FOXP3+ T cells in periphery blood was（0.30plusmn;0.19）% of CD4+ cell in VKH patients, and（1.41plusmn;0.52）% in control group, the difference was statistically significant（t=7.665,Plt;0.01）; after one month of treatment, the VKH patients group was（1.28plusmn;0.54）% which close to the control group. However there were two patients whose CD4+CD25+ T cells increased extraordinarily after one month of treatment. Conclusions The proportion of CD4+CD25+ FOCP3+ T cells in periphery blood in VKH patients were lower than control group obviously before treatment, but were close to control group after treatment. Those results indicated that VKH diseases may be associated with the decreased proportion of CD4+CD25+ regulatory T cells.
Objective To examine the levels of interferon-gamma; (INF-gamma;), tumor necrosis factor-alpha; (TNF-alpha;) and interleukin-6(IL-6) in serum of patients with acute uveitis before and after treatment, and to explore the possible roles of those cytokines in the initiation and progression of the uveitis. Methods A series of 75 patients with acute uveitis,and 30 healthy persons from our hospital were investigated. The levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase and convalescent phase were measured by the enzymelinked immunosorbent assay. Result The serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase were significantly higher than that of the convalescent phase and the healthy controls (F=65.805/50.418/155.381, P=0.000). A significant negative correlation was found between the serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase with their initial visual acuity(r=-0.656, -0.592 and -0.653, Plt;0.01). There was also a positive correlation among the serum levels of INF-gamma;, TNF-alpha; and IL-6(r=0.340, 0.467 and 0.338, Plt;0.05). Conclusions There are high serum levels of INF-gamma;, TNF-alpha; and IL-6 in patients with acute uveitis, and the cytokines levels were decreased after the treatment. The results suggested that the INF-gamma;, TNF-alpha; and IL-6 involved in initiation and progression of uveitis.
One hundred and thirty patients with uveitis in north-western zone of our country were analyzed based on anatomical classification and their causes. It was found that anterior uveitis was the commonest type in uveitis,accounting for 86.15% of total patients. Intermediate uveitis, pan-uveitis and posterior uveitis accounted repectively for 6.92%, 3.85%and3.08% of the total patients. Rheumatic arthritis was the most frequently accompanied systemic disease in patients with uveitis,showing a possibly causative link between them in their pathogenesis.
（Chin J Ocul Fundus Dis,1994,10:156-158）
Experimental uveitis was induced in rabbits by bovine serum albumin. Ocular inflammation,protein content of aqueous humor,T lymphocyte transformation and serum circulating immune complex were reduced markedly after the treatment of tetrandrine (Tet, 50mg/kg/d,ip)and dexamethasone(Dex, 5mg/kg/d,ip)for 8 days. Four days after withdrawal of Tet and Dex the protien content of the aqueous humor and serum eiucrlating immune complexes rose again,but these parameters in Tet group is lower than that in Dex group. The pathological
study showed that inflammation of choroid in Tet treated group was lighter than that in untreated group. These results suggest that Tet is an effective inhibitory agent on bovine serum albumin-induced experimental uveitis. Its mechanism may be related to the suppression of cellular and humoral immune function aside from antiinflammation.
（Chin J Ocul Fundus Dis,1994,10:149-152）
Objective
To investigate the cellular phenotype involved in experimental autoimmune uveoretinitis (EAU) and apoptosis of infiltrating cells in this inflammation．
Methods
Immunohistochemical staining and in situ apoptosis staining were performed using monoclonal antibodies to monocytes and macrophages (EDI),MHC calss -II antigen (OX6),T lymphocytes (R73) and TACS 1 Klenow kit on both ocular sections and wholemounts of 16 Lewis rats after immunization with interphotoreceptor retinod-binding protein(IRBP).
Results
EAU was induced in 12 of 16 Lewis rats with a clinical inflammation score being 1.29plusmn;0 .7.Influx of monocytes,lymphocytes and MHC class II+ cells into the uvea and retina was noted after immunization with IRBP.Apoptosis of infiltrating cells was observed in the uvea and retina and more apoptotic cells were present in the iris and ciliary body compared with the choroid and retina.
Conclusion
A number of cells including monocytes,macrophages,lymphocytes and MHC class II+ cells are involved in EAU induced by IRBP.Apoptosis of infiltrating cells occurs at early stage of EAU,which may greatly contribute to the rapid regression of the inflammation induced by IRBP.
(Chin J Ocul Fundus Dis，2000，16：1-70)
Objective
To investigate the expression and significance of inducible co-stimulator (ICOS) in experimental autoimmune uveoretinitis (EAU). Methods
EAU was induced in 24 Lewis rats (immune group) by immunization with retinal S-antigen (50 mu;g) and complete Freundprime;s adjuvant, and another 4 rats were in the control group. Anterior segment of the ratsprime; eyes were observed by split microscope every day. Immunohistochemical staining was performed using polyclonal antibodies to ICOS on the sections of the spleen which were obtained from the rats in immune group at the 7th, 12th, 15th and 21st days after immunisation respectively. Western blotting was performed to investigate the dynamic expression of ICOS protein in the spleen. The same procedures were made at the corresponding time points in the rats in control group.
Results
A few ICOS positive cells were observed in the normal spleen. The number of ICOS positive cells in immune group increased obviously at the 7th and 12th days after immunization, reached the peak at the 15th day, and decreased at the 21st day which was still higher than that in the control group. The result of Western blotting showed that the dynamic changes of ICOS protein was identical with the changes of positive-cell number detected by immunohistochemistry.
Conclusions
The enhanced expression of ICOS happens before EAU occurs, which increases when the inflammation occurs and deteriorates, and decreases at the alleviative stage of EAU. It suggests that ICOS participates in the formation, development and disappearance of EAU and plays an important role in the incidence of EAU.
(Chin J Ocul Fundus Dis, 2005,21:114-117)
The knowledge of uveitis of Chinese eye doctors has been improved in general. While the usage of glucocorticoid agents was more reasonable, other non-corticoid immunosuppressant get more attention recently. The usage of antibiotics also has being reduced gradually. The international impact of our uveitis research has been enhanced. However there are still some problems, such as big difference between different regions of uveitis research, still many misunderstandings on the treatment of uveitis complications, and the reasonable evaluation of intravitreal injection with glucocorticoid needs emphasis. In China Behcetprime;s disease and Vogt-Koyangi-Harada syndrome are the most common uveitis subtypes which can lead to blindness,but some rare subtypes of uveitis are also increasing such as syphilitic uveitis, acquired immune deficiency syndrome（AIDS），mycotic endophthalmitis and masquerade syndrome. In the future we need cooperative studies between multicenters to investigate the effectiveness of different treatment strategies for Behcetprime;s disease and Vogt-Koyangi-Harada syndrome, and to optimizing the best therapeutic schedule. We also need to pay more attentions to the clinical features of those uveitis subtypes which increased recently；and to investigate the prevention and therapeutic effect of induction of immune tolerance to uveitis.
Clinical materials of 198 patients with anterior uveitis were amdysed. The etiologic factors of disease, were estimated by history of the disease,clinical manifestation,concurrent diseases and laboratory findings.The main relevant causes were found successively to be rheumatlc arthritis (57 cases,28.79%), Fuchs syndrome (15 cases,7.58%) and herpes simplex virus infection (10 cases,5.05%).The diagnosis,treatement and etiology of anterior uveitis were discussed,and it was suggested that early diagnosis and appropriate treatment
are key to prevent loss of sight.
（Chin J Ocul Fundus Dis,1994,10:159-161）
