PURPOSE: Transforming growth factor-beta2 is known to be present at elevated levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and diabetes but not in uveitis-related secondary glaucoma. We investigated total TGF-beta2 levels and levels of the active form of TGF-beta2 in the aqueous humor of eyes with different types of glaucoma. METHODS: The concentration of the total and active form of TGF-beta2 was measured in 63 patients with primary open angle glaucoma, neovascular glaucoma complicated with diabetes (NVG), and secondary open angle glaucoma complicated with uveitis (SOAG) using a double antibody 'sandwich-indirect' ELISA method. RESULTS: The levels of total TGF-beta2 in the aqueous samples of POAG, NVG, and SOAG were elevated. The levels of active TGF-beta2 in the aqueous samples of POAG, and NVG were also elevated, whereas the level of active TGF-beta2 was within the normal range in the aqueous samples of SOAG. CONCLUSIONS: These results suggest that the level of TGF-beta2 may play a role in the pathology of various types of glaucoma.
Uveitis/*metabolism ; Transforming Growth Factor beta/*metabolism ; Severity of Illness Index ; Middle Aged ; Humans ; Glaucoma, Open-Angle/*metabolism ; Glaucoma, Angle-Closure/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Diabetic Retinopathy/*metabolism ; Biological Markers/metabolism ; Aqueous Humor/*metabolism ; Aged, 80 and over ; Aged ; Adult

PURPOSE: Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) METHODS: EIU was induced in female Lewis rats by single footpad injections of 200 microgram of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients. RESULTS: Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region. CONCLUSIONS: TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.
Animals ; Disease Progression ; Enzyme Inhibitors/*therapeutic use ; Female ; GTP-Binding Proteins/*antagonists & inhibitors/*metabolism ; Lipopolysaccharides ; Rats ; Rats, Inbred Lew ; Transglutaminases/*antagonists & inhibitors/*metabolism ; Uveitis/chemically induced/*enzymology/pathology

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

PURPOSE: Demonstrate unequivocally the generation of nitric oxide in experimental autoimmune uveoretinitis by electron spin resonance spectroscopy (ESR) using ferrous iron complex of N-methyl-D-glucamine dithiocarbamate, (MGD)2-Fe2+, as a spin trap. METHODS: Experimental autoimmune uveitis was induced in Lewis rats, and at the peak of the intraocular inflammation, the animals received intravitreous injections of the spin trap. The retina and choroid dissected from the enucleated globes were subjected to ESR. Similarly, the retina and choroid obtained at the peak of experimental autoimmune uveo-retinitis (EAU) were placed in a vial containing luminal, and chemiluminescence was counted on a Packard liquid scintillation analyzer. RESULTS: The ESR three-line spectrum (g=2.04; a(N)=12.5 G) obtained was characteristic of the adduct [(MGD)2-Fe2+-NO]. The majority of this signal was eliminated by the inducible nitric oxide synthase (iNOS) specific inhibitor aminoguanidine injected inflamed retina was detected when compared with that of the non inflamed controls. The chemiluminescent activity was further increased two-fold by the addition of bicarbonate to the inflamed retina; the phenomenon is attributable only to the presence of a high steady-state concentration of peroxynitrite. CONCLUSIONS: The study shows an unequivocal presence of nitric oxide in EAU retina and choroid and the generation of peroxynitrite. High levels of these reactive nitrogen species generated in the inflamed retina and choroids are certain to cause irreversible tissue damage, especially at the susceptible sites such as photoreceptors.
Uveitis/immunology/*metabolism ; Thiocarbamates ; Spin Trapping ; Spin Labels ; Sorbitol/analogs & derivatives ; Retina/metabolism ; Reactive Nitrogen Species/*metabolism ; Rats, Inbred Lew ; Rats ; Peptide Fragments/immunology ; Humans ; Electron Spin Resonance Spectroscopy ; Choroid/metabolism ; Autoimmune Diseases/immunology/*metabolism ; Arrestin/immunology ; Animals

A disease may be closely related to the change of season, as metabolism in human body may variously change with the season and the weather. Especially in the field of ophthalmology, several diseases have close relationship to the season in its incidence. In Korea, however, there has not been a report on seasonal distribution and incidence of eye diseases. The author made investigation upon seasonal, sex and age incidence of several eye diseases in the patients who were seen at Woo-Sok Hospital and two other eye clinics during the past five years. The results were as follows: 1. Among a total of 35, 157 patients, the seasonal, sex and age incidence of hordeolum, chalazion, phlyctenular kerato-conjunctivitis, uveitis, herpetic keratitis and central serous retinopathy were investigated. 2. Hordeolum shows the highest incidence in the winter season, and higher incidence particularly in the patients with blepharitis. 3. Chalazion has the highest incidence in the third decade, but no remarkable seasonal variation. 4. Phlyctenular kerato-conjunctivitis has the highest incidence in the spring season. 5. Uveitis has the highest incidence in the winter, especially in the fourth decade. 6. Herpetic keratitis is frequently developed in the spring and autumn, especially in the male of fourth decade. 7. Central serous retinopathy has the highest incidence in the winter season in healthy young adult male.
Blepharitis ; Central Serous Chorioretinopathy ; Chalazion ; Eye Diseases* ; Hordeolum ; Human Body ; Humans ; Incidence ; Keratitis, Herpetic ; Korea ; Male ; Metabolism ; Ophthalmology ; Seasons* ; Uveitis ; Weather ; Young Adult

OBJECTIVETo explore the effect of Tripterygium wilfordii polyglycoside (TWP) on level of serum interleukin 2 (IL-2), and tumor necrosis factor alpha (TNF-alpha) in patients of acute anterior uveitis (AAU).

METHODSPatients of AAU were randomly divided into two groups. The treated group (n = 50) was mainly treated with TWP and the control group (n = 50) treated with bimolani. The level of IL-2 and TNF-alpha before and after treatment were determined and compared between the two groups and also compared between the treated group and normal group consisted of 50 healthy subjects.

RESULTSLevels of IL-2 and TNF-alpha in the treated group before treatment were 1.31 +/- 0.27 micrograms/L and 1.20 +/- 0.65 micrograms/L, and after treatment 1.19 +/- 0.27 micrograms/L and 0.96 +/- 0.54 microgram/L, those in the control group were 1.31 +/- 0.26 micrograms/L and 1.22 +/- 0.66 micrograms/L before treatment and 1.20 +/- 0.27 micrograms/L and 0.98 +/- 0.51 microgram/L after treatment respectively. Comparisons of the two parameters before and after treatment in both groups showed significant difference (P < 0.05 in TWP group and P < 0.01 in bimolani group). The two parameters in both treated groups were all higher than those in the normal group before treatment (P < 0.05), but showed insignificant difference after treatment (P > 0.05).

CONCLUSIONAbnormal changes of IL-2 and TNF-alpha exist in AAU patients, TWP could suppress both parameters markedly therefore has a reliable effect in treatment of AAU.

Acute Disease ; Adolescent ; Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycosides ; therapeutic use ; Humans ; Interleukin-2 ; blood ; Male ; Middle Aged ; Phytotherapy ; Tripterygium ; chemistry ; Tumor Necrosis Factor-alpha ; metabolism ; Uveitis, Anterior ; blood ; drug therapy

OBJECTIVETo investigate the inhibitory effect of lycium pigment on lipopolysaccharide (LPS)-induced uveitis in rats and its mechanism.

METHODThe rat uveitis model was established by 30-day oral administration of lycium pigment (50, 100, 200 mg x kg(-1)) and footpad injection of LPS. Ocular tissues were collected for a histopathological inspection. The protein, nitric oxide and ADMA in aqueous humor, level of inducible nitric oxide synthase (iNOS) in retina, activities of serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and content of malondialdehyde (MDA) were determined by using Western blot, ELISA and biochemical methods.

RESULTAccording to the pathological study, lycium pigment (50, 100, 200 mg x kg(-1)) could notably reduce the inflammatory cell infiltration around corpus ciliare matrix of uveitis rats, and the concentration of protein and nitric oxide, and increased ADMA in aqueous humor. Lycium pigment (100, 200 mg x kg(-1)) could significantly inhibit the expression of iNOS in ocular tissues. In addition, lycium pigment (100, 200 mg x kg(-1)) also decrease the activities of serum T-AOC, SOD, GSH-PX, and the content of lipid peroxide MDA.

CONCLUSIONLycium pigment has the inhibitory effect on LPS-induced uveitis in rats. Its mechanism is related to the regulation of nitric oxide/ADMA pathway and the improvement of oxidation resistance.

Animals ; Glutathione Peroxidase ; genetics ; metabolism ; Humans ; Lipopolysaccharides ; adverse effects ; Lycium ; chemistry ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Pigments, Biological ; administration & dosage ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; genetics ; metabolism ; Uveitis ; chemically induced ; genetics ; metabolism ; prevention & control

OBJECTIVETo study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU).

METHODSThe EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions.

RESULTSSlighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 μg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 μg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 μg/L; =0.01). The PCR results showed the same tendency.

CONCLUSIONYanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Eye ; pathology ; Female ; Immunization ; Inflammation ; pathology ; Interferon-gamma ; genetics ; metabolism ; Interleukin-10 ; genetics ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Powders ; RNA, Messenger ; genetics ; metabolism ; Rats, Inbred Lew ; Spleen ; metabolism ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology ; Uveitis ; drug therapy ; genetics ; immunology

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an animal model of posterior uveitis and heme oxygenase-1 (HO-1) is a well-known anti-oxidant factor. However, there is no report a protective role of HO-1 on EAU in vivo. To verify that HO-1 is induced in EAU by interphotoreceptor retinoid-binding protein (IRBP), that an HO-1 inducers ameliorates the associated inflammation, and that an HO-1 inhibitor exacerbates this inflammation. METHODS: Forty four Lewis rats were given either 40 mol/kg hemin or 40 mol/kg SnPP (tin protoporphyrin IX) by intraperitoneal injection and twenty two uveitis control rats were injected with 0.5 mL of saline once daily 5-20 days after IRBP immunization inducing EAU. Three normal control rats were used for Western blotting and ELISA assay of HO-1. The clinical uveitis signs of inflammation were scored in the three groups from 0 to 4 on alternate three days. To confirm the clinical results, histological and immunohistochemical stain of HO-1 were performed on the day of peak inflammation and Western blotting and ELISA assay of HO-1 were performed on 6th, 12th and 18th day after IRBP immunization. RESULTS: Hemin, an inducer of HO-1, ameliorated the clinical signs of EAU. In contrast, SnPP-treated rats show that the severity of the clinical sign were exacerbated at the peak period of the disease. These results are roughly compatible with histological, immunoblotting, and immunohistochemical evaluations and an ELISA assay of HO-1. CONCLUSIONS: We suggest that HO-1 plays an important protective role in EAU.
Animals ; Autoimmune Diseases/diagnosis/*drug therapy/metabolism ; Blotting, Western ; Disease Models, Animal ; Enzyme Inhibitors/*administration & dosage ; Enzyme-Linked Immunosorbent Assay ; Heme Oxygenase-1/*biosynthesis/drug effects ; Hemin/*administration & dosage ; Immunohistochemistry ; Injections, Intraperitoneal ; Male ; Metalloporphyrins/*administration & dosage ; Microscopy, Acoustic ; Protoporphyrins/*administration & dosage ; Rats ; Rats, Inbred Lew ; Retinitis/diagnosis/*drug therapy/metabolism ; Treatment Outcome ; Uveitis, Posterior/diagnosis/*drug therapy/metabolism

Clinical features and prognosis of HLA-B27 positive anterior uveitis (AU) were assessed compared with HLA-B27 negative AU in a Korean population, based on the medical records of AU patients seen at a university hospital. Twenty-seven HLA-B27 negative, idiopathic AU patients (group I) and 55 HLA-B27 positive AU patients (group II) were studied. HLA-B27 positive group was further divided into 29 with associated systemic disease (seronegative spondyloarthropathy) (group IIA) and 26 without associated systemic disease (group IIB). Significantly more severe anterior chamber inflammation in terms of anterior chamber cells (P=0.006) and hypopyon formation (P=0.034) was observed with higher frequency of AU attacks (P=0.007) in the HLA-B27 positive group than in the HLA-B27 negative group. Systemic/periocular steroids were required in significantly more patients in the HLA-B27 positive group than in the HLA-B27 negative group (P=0.015). However, no significant differences were observed for final ocular and visual outcomes between these two groups. Associated systemic disease made no significant difference in the clinical features and prognosis in the HLA-B27 positive AU patients. In conclusion, despite more severe inflammation and a higher recurrence rate, HLA-B27 positive AU shows similar good final ocular and visual outcomes compared to HLA-B27 negative, idiopathic AU in a Korean population.
Adolescent ; Adult ; Aged ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asian Continental Ancestry Group ; Case-Control Studies ; Female ; HLA-B27 Antigen/genetics/*metabolism ; Humans ; Immunosuppressive Agents/therapeutic use ; Korea ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Steroids/therapeutic use ; Uveitis, Anterior/*diagnosis/drug therapy/metabolism ; Visual Acuity