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)
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.
Vogt-Koyanagi-Harada syndrome (VKH) is an autoimmune disorder primarily characterized by bilateral granulomatous uveitis, which can lead to severe visual impairment and related complications. Traditional treatment typically involves glucocorticoid combined with immunosuppressants, but these therapies are associated with significant side effects, limited efficacy, and poor long-term prognosis. In recent years, biologic agents have emerged as a promising treatment for refractory VKH due to their targeted action, high efficacy, and low toxicity. Tumor necrosis factor-alpha (TNF-α) inhibitors, such as infliximab and adalimumab, have shown significant benefits in controlling inflammation, improving vision, and reducing steroid dependence, making them a key option for difficult-to-treat VKH. Among interleukin (IL) blockers, tocilizumab has demonstrated potential in patients who do not respond to traditional treatments. Rituximab, a B-cell targeting agent, has shown good efficacy and safety in patients resistant to TNF-α inhibitors. Additionally, research into novel biologics targeting the IL-23/IL-17 axis and IL-33 offers new directions for VKH therapy. While biologics provide clear advantages in VKH treatment, further research is needed to explore their long-term safety, cost-effectiveness, and optimal treatment regimens. Large-scale randomized controlled trials are required to validate their efficacy and identify personalized treatment strategies to improve long-term patient outcomes.
ObjectiveTo observe the clinical evolution process and imaging characteristics of choroidal lesions in different subtypes of serpiginous choroiditis (SC), and to explore the clinical significance of subtype classification. MethodsA retrospective, uncontrolled and observational study. A total of 45 eyes of 25 SC patients diagnosed in Yunnan Eye Hospital from May 2009 to September 2021 were included in the study. According to the initial location of the lesion and fundus images, including fundus color photography, fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and other examination results. SC was divided into peripapillary serpiginous choroiditis, macular serpiginous choroiditis and ampiginous choroiditis. According to the shape of the lesions at the first diagnosis, it can be divided into new lesions with only infiltrating edema, old lesions with only atrophy and recurrent lesions with coexistence of edema and atrophy. the imaging features, development and complications of different subtypes of ocular lesion were observed. ResultsAmong the 45 eyes of 25 cases, 15 cases were male and 10 cases were female, 20 cases of binocular and 5 cases of monocular, age was 42.3±5.7 years old. There were 21 eyes with active lesions, of which 5 eyes were new lesions and 16 eyes with recurrent lesions; 24 eyes were old lesions. Concurrent optic disc edema occurred in 3 eyes; mild vitreitis occurred in 5 eyes; retinal occurred vasculitis in 3 eyes; choroidal neovascularization occurred in 3 eyes. Among the 16 cases (64%, 16/25) of the peripapillary serpiginous choroiditis, 2 cases (2 eyes) were monocular, and 14 cases (28 eyes) were binocular. Active lesions were found in 16 eyes, of which patients with binocular lesions only one had active lesions. The choroidal lesions that were close to the optic disc or around the optic disc, expanded outwards centrifugally with the prolongation of the disease course, and can progress to the macula. The edge of the lesion was tortuous, with a geographic-like, amoeboid-like and finger-like, polypoid or propeller-like shape. Active lesions in FFA showed weak fluorescence in the early stage and strong fluorescence in the late stage; the old lesions showed weak fluorescence in the early stage and mottled fluorescence in the late stage, and mostly strong fluorescence on the edge. OCT showed thickening of active lesions and thinning of old lesions. Among the 4 cases (16.0%, 4/25) of macular type, 2 cases (2 monocular eyes) had active lesions; 2 cases (4 eyes) had lesion in both eyes, among them, 1 case (2 eyes) had old lesion, and the other case had alternate active lesions. The initial lesions were all located in the off-center of the macula, and most of them were disk-shaped and progressing centrifugally to the periphery. The FFA and OCT imaging findings of the lesions were similar to those of the peridisc type. Among the 5 cases (20.0%, 5/25) of ampiginous choroiditis, 1 case (1 eye) was monocular and 4 cases (8 eyes) were binocular. These lesions were multiple old lesions of varying sizes, gray-white with pigmentation, with clear borders in the posterior pole. Among them 4 eyes have new active lesions appeared near the old lesions. The old lesions showed weak fluorescence with clear borders, and the fluorescein leakage at the late edge formed a strong fluorescence ring; the active lesions showed weak fluorescent spots with blurred edges, and the fluorescence was slightly enhanced in the late stage. In old lesions, atrophy of the photoreceptor layer, RPE and choroid can be seen, and RPE hyperplasia in some areas. ConclusionsSC subtype is a classification of the location of the first lesion, but the characteristics of the repeated attack of this disease can lead to the annihilation of each subtype due to the continuous expansion of the lesion. The phenomenon that the fundus active lesions only occur in one eye that can explain the clinical manifestations of asymmetric morphology of binocular lesions. The characteristics of binocular subtype warn that the predilection site of the healthy eye should be paid attention to.
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 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 observe the efficacy of the anti-tumor necrosis factor-alpha; monoclonal antibody (TNF-alpha; MCAb) in the treatment of experimental autoimmune uveoretinitis (EAU). Methods EAU animal models were induced by interphotoreceptor retinoid-binding protein (IRBP) R16 peptide with immunization. The rats were divided into 2 groups according to the injection times. TNF-alpha; MCAb was administered intravenously on day 6 or 4, 6 and 8 post-immunization respectively, and then to observe the clinical expression by slit-lamp microscope. Meanwhile, take the rats which did not accept TNF-alpha; MCAb as control group. Delayed type hypersensitivity (DTH) responses were measured on day 13 post-immunization of IRBP R16; the rats were killed on day 14 post-immunization of IRBP R16, and then enucleated the eyes for histopathological examination. To detect the cytokine level of IFN-gamma;, IL-4 in serum and IFN-gamma; in aqueous humor by enzyme-liked immunosorbent assay (ELISA) on day 14 post-injection. The hyperplasia responses of antigen specific lymphocyte of draining lymph node cells were detected. Results The TNF-alpha; MCAb group had mitigated ocular inflammation and decreased pathological grades compared with the control group; the IFN-gamma; concentrations in aqueous humor and serum were decreased, IL-4 was increased in serum; DTH responses were decreased; the hyperplasia responses of draining lymphocytes to IRBP R16 peptide were decreased, all the differences were statistically significant (P＜0.01). The rats accepted TNF-alpha; MCAb thrice had much better curative effect than the rats injected once (P＜0.05). Conclusions Injection of TNF-alpha; MCAb can inhibit ocular inflammation and specific immune cells of EAU remarkably and change the Th1/Th2 balance. Many times injections of TNF-alpha; MCAb were more effective than once.
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)
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.
Uveitic macular edema (UME) is a major reason of permanent visual loss. Early treatment is essential for achieving a good visual outcome, but some patients are resistant or nonresponsive to the treatment, which is called refractory UME (RUME). Intravitreous injection of glucocorticoids can improve the intraocular drug concentration and avoid systemic side effects. Immunosuppressive agents have a certain role in improving RUME by inhibiting immune cells through a variety of ways. Non-steroidal anti-inflammatory drugs, carbonic anhydrase inhibitors and new biological agents also can improve RUME outcome, but their effectiveness and safety need to be confirmed by large scale randomized clinical trials. Vitrectomy can improve RUME outcome but whether peeling of internal limiting membrane is necessary or not is still controversial. Peeling the inner limiting membrane can eliminate the potential incentive for macular edema and remove the barrier. But the process of stripping may injury the retinal neurepithelium. To eliminate edema and protect the visual function, we should analysis the causes of RUME and treat it individually.