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 study the clinical classification and etiologies of uveitis based on 1214 uveitis patients reffered to Zhongshan Ophthalmic Center. Methods A retrospective analysis was made on the patients with uveitis, coming from all over China between January 1996 and December 2001. All kinds of uveitis were classified according to the anatomical criteria and etiological criteria. The relevant data of these patients, such as the age at uveitis onset and sex were also analyzed. Results The total number of the patients is 1214 (male 698, female 516), with the average age at disease onset being 34.43. Anterior uveitis, the most common type, was seen in 546 cases, accounting for 44.98% of all the patients, followed in descending order by panuveitis (530 cases, 43.66%), intermediate uveitis(78 cases, 6.43%) and posterior uveitis(60 cases, 4.94%). Etiological factors and clinical entities were identified in 703 patients, accounting for 57.91% of all the patients, and the other 511 patients were idiopathic ones. The most common types of anterior uveitis were idiopathic uveitis(316 cases, 57.88%), followed by Fuchs syndrome(85 cases) and ankylosing spondylitis(45 cases). BehCcedil;et disease(218 cases, 41.13%) and Vogt-Koyanagi-Harada syndrome(196 cases, 36.98%) were the most common entities in panuveitis. Neither etiological factors nor clinical entities could be identified in the patients with intermediate uveitis and those with posterior uveitis. Conclusions Uveitis occurs mostly in young and middle-aged adults. In general, a predilection was seen in the male as compared with the female in the development of uveitis. Idiopathic anterior uveitis, BehCcedil;et disease and Vogt-Koyanagi-Harada syndrome are the most common entities of uveitis seen in China. Classification based on etiological and anatomical factors may provide a reasonable system for the study of uveitis. (Chin J Ocul Fundus Dis, 2002, 18: 253-255)
Objective To investigate the impact of bone marrow mesenchymal stem cell transplantation on a rat model of experimental autoimmune uveitis (EAU) and analyze its immune regulatory mechanisms in vivo.Methods Eighteen Lewis rats were randomly divided into three groups: model control group, intervention group and normal control group, six animals in each group. Human retinal S-antigen peptide (HS-AgP35, 1 mg/ml) was mixed and emulsified with complete Freundprime;s adjuvant and injected into hind foot pad of rats on the first and eighth day to establish the animal model of EAU. For bone marrow mesenchymal stem cell transplantation, 1 ml of cell suspension (2times;106 cells/ml) was injected into tail vein of the intervention group rats on the first day when the emulsified S-antigen was injected. EAU manifestation, pathological change and IFN-gamma; level were evaluated and compared among those three groups after two weeks. Results No abnormal signs were found in the eyes of rats in normal control group. The manifestation grading of the intervention group (two rats at grade 0, three rats at grade 0.5, one rat at grade one) was significantly different from the model control group (one rat at grade one, one rat at grade two, three rats at grade three, one rat at grade four) (P=0.015). The retina of rats in normal control group was ordinary under light microscope. The histopathologrical grading of the intervention group (one rat at grade 0, four rats at grade 0.5,one rat at grade one) and the model control group (four rats at grade three, two rats at grade four) was also statistically different (P＜0.01). Furthermore, the IFN-gamma; level in peripheral blood of the intervention group rats declined significantly compared to the model control group (t=9.0574, P=0.01). Conclusions Bone marrow mesenchymal stem cells can inhibit EAU significantly, possibly by lowering the level of IFN－gamma;, thereby reduce the severity of uveitis and improve the condition of uveitis in rats.
Objective To observe the clinical features, the complications and treatment effects of intermediate uveitis. Methods The clinical data of 36 patients (66 eyes) with intermediate uveitis were retrospectively analyzed，including the clinical features, fundus fluorescein angiography (FFA) features, complications，treatment effects and prognosis. The patients, 21 males and 15 females, aged from 8 to 70 years，with the mean age of 34.8 years. There were 30 cases with bilateral lesions and 6 cases with unilateral lesions. Results The main clinical manifestation were vitreous opacity, peripheral retinal venous lesions, optic disc edema, macular edema and posterior subcapsular cataract. The results of FFA showed that peripheral retinal venous lesions, optic disc hyperfluorescence, cystoid macular edema and retinal vein staining. After the treatment, the visual acuity of 31 cases（60 eyes，90.9%) were improved, 4 cases（5 eyes，7.6%) were stable and 1 case（1 eye，1.5%) was worsening. The main complications were cystoid macular edema, posterior subcapsular cataract and vitreous hemorrhage which leads to visual damage. Conclusions Intermediate uveitis was a common bilateral and chronic progressive intraocular inflammation，the anterior vitritis, pars plana and peripheral retinal vascular changes were mainly involved. Early diagnosis and proper treatment may prevent the permanent visual damage.
Objective To investigate the effect of bromocriptine on rats with experimental autoimmune uveoretinitis.Methods Tweenty-four Wistar rats were immunized by bovine soluble antigen and randomly divided into treatment and control group. The rats in treatment group took bromocriptine orally with the dosage of 5 mg/(kg·d), which could inhibit prolactin (PRL) deliverance, while the rats in control group took glucose solution orally with the dosage of 50 g/(L·d). The clinical changes of all the rats and the delayed type hypersensitivity (DTH) response were detected. The rats were anesthetized and killed after im munized for 21 days, and the eyes were removed and examined histologically.Results The occurrence of EAU and histology scores of rats in treatment group were lower than the controls (P＜0.05,P＜0.001). The DTH response of two groups had no statistic difference (P＞0.05). Conclusions Bromocriptine can generally inhibit PRL deliverance, and may also inhibit the occurrence of EAU in rats through neuroendocrine-immune regulating network. (Chin J Ocul Fundus Dis，2003，19：34-37)
Glucocorticoids (GCS) are the main treatment for non-infectious uveitis (NIU). However, long-term GCS treatment may induce systemic side effects including hypertension, hyperlipidemia and diabetes. Patients may develop cataract, ocular hypertension or glaucoma because of topical application of GCS. Rapamycin (RAPA) exhibits immunosuppressive, antiangiogenic and antiproliferative effects. Animal experiments and clinical trials have shown that RAPA has therapeutic potential for NIU, especially the treatment of intravitreal injection. In particular, intravitreal injection of RAPA can result in minimal systemic exposure and reduce adverse events. Meanwhile, systemic unwanted effects should be concerned about. In recent years, some studies have attempted to employ nanostructured carriers to improve penetrating abilities of RAPA and efficacy of treatment for ocular posterior segment diseases. These carriers include micelles, liposomes, nanocrystals, polymeric nanoparticles, magnetic nanoparticles and so on. Whether they can load RAPA for treating NIU deserves further study and exploration.
ObjectiveTo preliminarily investigate the mechanism of MMP-9 blocking CD73 detachment from RPE cells surface and preventing and treating experimental autoimmune pigment membranitis (EAU).MethodsRPE cells isolated from wild-type C57BL/6 and CD73 gene knockout (CD73-/-) mice were cultured in vitro, and treated with lipopolysaccharide and TNF-α to induce CD73 detachment from RPE surface. According to whether MMP-9 inhibitor CTK8G1150 was added at the same time (the final concentration was 5.0 mol/L) or not, RPE cells cultured in the two types of mice were respectively set as MMP-9 inhibitor intervention group and non-intervention control group. The cells in each group were treated with the intervention of a solvent, 1 μmol/L adenosine monophosphate (AMP), 1 μmol/L AMP, and 3 μmol/L 5' -α,β-methylene adenosine diphosphate (APCP) (AMP+APCP). The stimulating effect of RPE cells in different groups on CD4+ T cell proliferation was detected by tritiated thymidine incorporation. Adoptive immune induced EAU in wild-type B6 mice and CD73-/- mice, respectively. The receptor mice were randomly divided into the MMP-9 inhibitor intervention group and the non-intervention control group, and CTK8G1150 or the solvent were injected into the subretinal cavity 4, 7 and 10 days after adoptive immunity. CD73 mRNA and protein expression in RPE cells of recipient mice were detected by real-time quantitative PCR (RT-PCR) and Western blot. One-way ANOVA was used to analyze all experimental data.ResultsWhen the stimulation mode was AMP, the proliferation of CD4+ T cells in the C57BL/6 MMP-9 inhibitor intervention group decreased significantly compared with the non-intervention group (F=13.28, P＜0.01). When the stimulation mode was solvent and AMP+APCP, there was no statistically significant difference in the proliferation capacity of CD4+ T cells between the two groups (F=7.78, 6.58; P＞0.05). There was no statistically significant difference in the proliferation capacity of CD4+ T cells between the CD73-/- MMP-9 inhibitor intervention group and the non-intervention group (F=5.24, 6.12, 7.04; P＞0.05). RT-PCR results showed that there was no statistically significant difference in the relative expression of CD73 mRNA in RPE cells between the MMP-9 inhibitor group and the non-intervention control group (F=6.54, P>0.05). Western blot results showed that the expression of CD73 protein in RPE cells in the MMP-9 inhibitor group of B6 receptor mice was significantly increased compared with the control group (F=15.24, P＜0.01).ConclusionMMP-9 inhibitor blocks CD73 detachment from RPE cells surface and has a protective effect on EAU.
Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis, typically as chronic anterior uveitis with insidious onset. Delayed and inadequate treatment may result in loss of patients' vision and even blindness. For refractory or severe uveitis related to juvenile idiopathic arthritis, systemic immunosuppressive agents should be used as early as possible. With the advantage of controlling ocular inflammation, avoiding ocular complications and reducing the use of traditional immunosuppressant drugs and glucocorticoid, tumor necrosis factor-α inhibitors have been new therapeutic options for uveitis associated with juvenile idiopathic arthritis, although methotrexate is known as the first-line approach. However, there are no internationally unified guidelines for clinical issues regarding the timing of application, reduction and withdrawal of tumor necrosis factor-α inhibitors, and no agreement on the application of tumor necrosis factor-α inhibitors in the management of ocular complications either. An in-depth understanding of the application status and progress of tumor necrosis factor alpha inhibitors in the treatment of juvenile idiopathic arthritis-associated uveitis has important clinical significance.
Objective To explore the consistency and significance of optical coherence tomography (OCT) and clinical and histopathological findings in adoptively transferred uveitis in mice. Methods The adoptively transferred experimental autoimmune uveitis (EAU) model was established by intraperitoneal injection of antigen-specific T cells in C57BL/6 mice. Since 9 days after transferred, inflammation of eyes was observed by indirect ophthalmoscope with +90D lens and record clinical scores every 3 days. The disease was divided into 6 phases including onset phase, early phase, pre-peak phase, peak phase, resolution phase and late phase of EAU, which respectively corresponding to clinical score 0.5, 1.0, 1.5 - 2.0, 2.5 - 3.0, 1.0 - 2.0 and less than 1.0. Since 9 days after transferred, the retina and retinal thickness (RT) was measured by spectralis OCT about 1 disc from the disc edge in 10 time points including 9, 11, 16, 21, 25, 30, 35, 40, 50 and 60 days after transferred. The OCT score was recorded as from 0.0 to 4.0. After transferred 9, 21 and 60 days, the mice were killed and eye balls were examined in histology. OCT score, clinical score and histology in the mouse were compared and analyzed. Results The disease was divided into onset phase, early phase, pre-peak phase and peak phase of EAU, which respectively corresponding to 9, 16, 21 and 26 days after transferred. In four phases, OCT score were 0.5, 1.0, 2.0 and 4.0 respectively. After transferred 30 days, which was in resolution phase of EAU, the inflammation cells in vitreous were decreased and OCT score was 3.0. After transferred 60 days, which was in late phase of EAU, inflammation cells in vitreous were disappeared and retina was atrophic topically. The histology showed the vitreous has slight inflammation cells and retinal structure was normal at onset of EAU. The vitreous has massive inflammation cells and retina structure was disorder at pre-peak of EAU. And in resolution phase of EAU, the inflammation cells in vitreous were slightly and retina was atrophic and thinned. The data in this study demonstrated that OCT score was well correlated with clinical score in EAU (r=0.957 9, P < 0.000 1). Conclusion OCT and clinical and histopathological findings in adoptively transferred uveitis in mice were consistency and OCT is contribute to evaluate the disease dynamically and quantifiably.