Noninfectious uveitis refers to a category of inflammatory diseases involving the uvea, with the exception of infectious factors or masquerade syndrome. The diagnosis and follow-up of noninfectious uveitis that involving retina or choroid require fundus imaging techniques. Fundus autofluorescence is a noninvasive imaging technique. Compared with fundus colorized photography, fundus fluorescein angiography and indocyanine green angiography, fundus autofluorescence indicates the functional status of retinal pigment epithelium and photoreceptor cells in a better way, thus playing a role in the pathophysiological mechanisms investigating, early diagnosis, disease progression monitoring and prognosis estimating of noninfectious uveitis, such as Vogt-Koyanagi-Harada disease, Behçet disease, multifocal choroiditis, punctate inner choroidopathy, birdshot chorioretinopathy, multiple evanescent white dot syndrome, acute zonal occult outer retinopathy, acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis.
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.
Objective To explore the frequency, clinical features, and characteristics of results of fundus fluorescein angiography (FFA) of uveitis related cystoid macular edema (CME). Methods The clinical data and FFA results of 67 patients (106 eyes) with posterior uveitis examined in our hospital from July 2002 to June 2005 were collected. The clinical features and characteristics of FFA images of CME were observed and analyzed. Results Among the106 eyes of 67 patients with uveitis,the CME was observed in 28 eyes (26.4%) of 18 patients, including 7 males and 11 females with the average age of (42.5plusmn;10.8) years. The dark area due to the choroidal fluorescence blocked by the macular edema was found at the early FFA phase, and th en followed by the punctate and sheetlike leakage of fluorescein; the capillar y was dilated at the venous phase, and the typical petaloid appearance was seen at the late phase because the fluorescein cumulated in several small vesicles in the macular area. After treated by corticosteroids and topical non-steroidal anti-inflammatory medicine and carbonic anhydrase inhibitors, the extent of CME diminished, and the visual acuity improved in varying degrees. Conclusi ons Uveitis may seriously harm the visual function, in which CME induces the damage of visual acuity. Early detection and timely treatment may prevent thepermanent visual damage. (Chin J Ocul Fundus Dis, 2006, 22: 394-396)
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 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.
PURPOSE: To investigate the influence of transforming growth factor-beta (TGF-beta;) on endotoxin-induced uveitis (EIU). METHODS: TGF- beta; was abstracted from humam platelets using Bio-gel P-60 chromatography. It was introduced either topically(drops) or intraperitoneally into the SD rats after footpad injection of lipopolysaccbaride(LPS). The inflammation in the anterior uvea was clinically evaluated with slitlamp every day. RESULTS :TGF-beta; obtained from Biogel P-60 chromatography displayed single band on SDS-PAGE,showing a molecular weight of 12 500 EIU occurs significantly earlier and more severe in the rats which only received LPS injection than in the TGF-beta; treated rats. The duration of the inflammation was also much longer in the untreated rats than in the treated rats (P＜0. 001). CONCLUSION: TGF-beta; purified from human platelets may partly prevent the development of EIU and effectively reduce the severity of the inflammation induced by LPS injection. （Chin J Ocul Fundus Dis,1996,12: 101-104)
ObjectiveTo investigate the expression of costimulatory molecules( B7，CD28, and CTLA-4) of peripheral blood lymphocytes in patients with Behcet′s disease(BD).MethodsLymphocytes were obtained in 24 patients with BD and 20 healthy individuals, and the expression of CD80(B7-1), CD86(B7-2), CD28 and CTLA-4 on T and B cells were detected by direct three-color immunofluorescence flow cytometry.ResultsSignificantly increased expression of CTLA-4 on CD 4+ T cells[(3.18±1.18)%]was found in BD patients compared with that in controls[(1.73±0.66) %](t=－3.722,P＜0.01). The expression of CD86 on CD19+B cells was also significantly increased in BD patients[(4.49±1.73)%]compared with that in controls[(2.40±1.49) %] (t=-2.071,P＜0.05). No significant difference in the expression of the other costimulatory molecules was found.ConclusionsInteraction of B7 and CD28 on peripheral lymphocytes promote the occurrence of uveitis in BD patients. Intervention with these costimulatory signals may lead to a new prevention or treatment for uveitis patients.(Chin J Ocul Fundus Dis, 2003,19:357-359)
Objective To observe the fundus imaging characteristics of different stages of syphilitic posterior uveitis. Methods Retrospective cases series. Forty-six eyes of 32 patients with syphilitic posterior uveitis were included. There were 14 patients (16 eyes) and 18 patients (30 eyes) were assigned to acute stage group (with the course ＜2 months) and chronic stage group (with the course ≥2 months) respectively. All eyes received the examination of indirect ophthalmoscopy, color fundus photography, fundus fluorescein angiography (FFA) and optical coherence tomography (OCT). All patients received regular anti-syphilitic treatment. Color fundus photography and OCT were followed after treatment. The fundus imaging characteristics of different stages of syphilitic posterior uveitis were observed. Results Indirect ophthalmoscopy and fundus color photography showed that in the acute stage group, there were 3/16 eyes with optic disc edema; 4/16 eyes with a yellowish, placoid lesion involving the macular. There were only some pigment alterations on the fundus after treatment. In the chronic stage group, there were 4/30 eyes with optic disc hyperemia, 3/30 eyes with cystoid macular edema. After treatment, the optic hyperemia vanished gradually, but there were still some pigment alterations. The FFA images of two groups showed various vascular leakages. In the chronic stage group, patients also showed hyper-fluorescence with cystoid macular edema. The patients with course 2 – 3 years have more transmitted fluorescence on FFA. OCT showed that all eyes in the acute stage group had lost the ellipsoid zone, with irregular granular reflectivity of the retinal pigment epithelium (RPE) layer, 6 eyes with subretinal fluid in the macular. After treatment, the ellipsoid zone and RPE layer structure recovered gradually. In the chronic stage group, all eyes showed widespread loss of the ellipsoid zone, pigment migration and (or) cystoid macular edema. After treatment, the ellipsoid zone showed partial recovery. The outer ellipsoid zone was still discontinuous in patients with long duration. Conclusions Syphilitic posterior uveitis patients generally had normal fundus, but some cases had a yellowish, placoid lesion involving the macular. FFA showed various vascular leakages, and the chronic stage group showed more transmitted fluorescence. The major OCT change was loss of the ellipsoid zone or with subretinal fluid. After treatment, fundus showed no abnormal manifestations except some pigment alterations; the ellipsoid zone structure recovered gradually in acute stage eyes, partially recovered in chronic stage eyes.
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.
ObjectiveTo study the distribution of pathogenic microorganisms in the ocular fluid of patients with acquired immunodeficiency syndrome (AIDS) and infectious uveitis.MethodsIt was a retrospective case analysis. From June 2018 to December 2019, 31 AIDS patients with infectious uveitis who were hospitalized or outpatient at Shanghai Public Health Clinical Center were included in the study. Among them, there were 30 males and 1 female; the average age was 38.51±11.17 years. There were 20 cases of panuveitis, 10 cases of posterior uveitis, and 1 case of infectious endophthalmitis. Serum CD4+T lymphocyte count (CD4+TC) were 0 - 239/μl during the same period. The second-generation gene sequencing technology was used to detect the collected intraocular fluid. Among 31 specimens, aqueous humor and vitreous humor were 27 and 4 respectively.ResultsAmong 31 specimens, 18 samples (58.1%, 18/31) of cytomegalovirus (CMV) were detected; varicella-zoster virus (VZV) were detected in 5 samples (16.1%, 5/31); Epstein-Barr virus were detected in 9 samples (29.0%, 9/31); human beta herpes virus type 6 (HHV6) were detected in 3 samples (9.7%, 3/31), human papillary molluscum virus (HPV), human polyoma virus, type G hepatitis virus were separately detected in 1 sample (3.2%, 1/31), all coexisting with other microorganisms. Parvovirus were detedcted in 8 samples (25.8%, 8/31); treponema pallidum were detedcted in 5 samples (16.1%, 5/31); toxoplasma gondii and Harmon coccidia were detedcted in 1 sample (3.2%, 1/31); synitelium Polycarpum were detedcted in 1 sample (3.2%, 1/31); mycobacterium tuberculosis complex, fungi, and microbacteria coexist were detedcted in 1 sample (3.2%, 1/31). Among the 18 CMV specimens, the number of gene sequences was more than 1059 (50.0%), and 104-1055 (27.7%). Among the 5 specimens of VZV, the number of gene sequences was＞1044 (80.0%). In one specimen, the mycobacterium tuberculosis complex, fungi, and microbacteria coexist, and the number of gene sequences were all＜100. The number of gene sequences of HHV6, HPV, human polyoma virus, type G virus, and parvovirus in all specimens was small. Among 31 specimens, 15 (48.4%) of pathogenic microorganisms were detected at least 2 species.ConclusionsCMV and VZV are the main pathogenic microorganisms of infective uveitis in patients with serum CD4+TC＜100/μl; treponema pallidum, toxoplasma gondii or other protozoa, mycobacterium tuberculosis, and fungi cause more infectious uveitis which are common in AIDS patients with serum CD4+TC＞100/μl. The coexistence of two or more microorganisms can be detected in the intraocular fluid of AIDS patients with infectious uveitis.