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Background: Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body: Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion: Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions.

Abstract Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. Graphical Abstract

Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo investigate the roles of sphingosine kinases (SphKs) and sphingosine-1-phosphate receptors (S1PRs) in endotoxin-induced uveitis (EIU) mice.EIU model was induced using an intraperitoneal injection of lipopolysaccharide (LPS). The expression of SphKs and S1PRs in the retina was assessed using quantitative polymerase chain reaction (qPCR) and immunofluorescence. The effects of S1PR antagonists on the expression of inflammatory cytokines in the retina were evaluated using qPCR and western blotting. Effects of leukocyte infiltration of the retinal vessels were evaluated to determine the effects of the S1PR2 antagonist and genetic deletion of S1PR2 on retinal inflammation.Retinal SphK1 expression was significantly upregulated in EIU. SphK1 was expressed in the GCL, IPL, and OPL and S1PR2 was expressed in the GCL, INL, and OPL. Positive cells in IPL and OPL of EIU retina were identified as endothelial cells. S1PR2 antagonist and genetic deletion of S1PR2 significantly suppressed the expression of IL-1α, IL-6, TNF-α, and ICAM-1, whereas S1PR1/3 antagonist did not. Use of S1PR2 antagonist and S1PR2 knockout in mice significantly ameliorated leukocyte adhesion induced by LPS.SphK1/S1P/S1PR2 signaling was upregulated in EIU and S1PR2 inhibition suppressed inflammatory response. Targeting this signaling pathway has potential for treating retinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the inhibitory effect of topically administered azithromycin (AZM), and moxifloxacin (MXF) against tumor necrosis factor-α (TNF-α) production in a rat model of endotoxin-induced uveitis (EIU). Methods: Thirty-six Wistar albino rats were divided into 6 equal groups. Groups 1, 2 and 3 were determined as sham, control group for topical AZM application and control group for topical MXF application, respectively. Sterile saline, topical AZM 1.5%, and topical MXF 0.5% were instilled 5 times daily for totally 6 days on both eyes of the rats in Group 4, Group 5, and Group 6, before and after inducing EIU by intravitreal injections of lipopolysaccharide, respectively. At 24 h after intravitreal injections, aqueous humor was collected from both eyes of each rat for the assessment of TNF-α concentration. Also, density of nuclear factor kappa B (NF-κB) in ciliary body, and the number of cells infiltrating the posterior segment of EIU rat eyes was assessed in one eye of each rat. Results: There was a significant reduction in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical AZM in comparison with those pretreated with sterile saline (139 ± 38.6 in Group 4 vs. 72 ± 12.6 in Group 5, p = 0.006). There was also a marked decrease in mean aqueous humor concentration of TNF-α in EIU rats pretreated with topical MXF (139 ± 38.6 in Group 4 vs.86.1 ± 35.5 in Group 6, p = 0.025). Also, evident suppressions were determined in mean density of NF-κB, and in mean number of cells in EIU rats pretreated either with topical AZM, or topical MXF. Conclusions: Topically applied AZM or MXF may be beneficial in the suppression of TNF-α production in aqueous humor. [ABSTRACT FROM AUTHOR]

The metabolism of 5-aminolevulinic acid (ALA) is more efficient when combined with sodium ferrous citrate (SFC). Our previous study revealed that oral administration of ALA, which has anti-inflammatory properties, and SFC (ALA/SFC) immediately before lipopolysaccharide (LPS) inoculation suppressed endotoxin-induced uveitis (EIU) in rats. However, the therapeutic effect of ALA/SFC post-administration remains unexplored. Hence, this study aimed to evaluate the therapeutic efficacy of ALA/SFC on EIU in rats, which were administered with a gastric gavage of ALA/SFC (100/157 mg/kg) or prednisolone (Pred, 10 mg/kg) after 4 h of LPS inoculation. The treatment groups showed ameliorated clinical scores, inflammatory cells, protein levels in the aqueous humor (AqH), and histopathologic evaluation 24 h after LPS inoculation. Furthermore, the treatment groups had reduced tumor necrosis factor-α, nitric oxide, prostaglandin E2, and interleukin-6 levels in the AqH. ALA/SFC demonstrated an anti-inflammatory effect equivalent to that demonstrated by Pred. These findings indicate that ALA/SFC exerts a therapeutic effect on EIU in rats, indicating its clinical usefulness in uveitis treatment. [ABSTRACT FROM AUTHOR]

Objectives: This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the Traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com). Materials and Methods: Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results: Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat's iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-γ and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveitis causes severe vision impairment, leading to blindness. Clinically, corticosteroids are its first-line treatment to reduce inflammation, but they can cause systemic and local side effects. Recently, 5-aminolevulinic acid (5-ALA) has received attention for its reported anti-inflammatory effects. However, the effects by 5-ALA on uveitis are still insufficiently understood. Therefore, this study aims to investigate whether 5-ALA inhibits endotoxin-induced uveitis (EIU) in rats. Results showed that 5-ALA dose-dependently suppressed the clinical score of EIU, decreased aqueous humor infiltrating cells and protein concentrations, and improved histopathological scores. In particular, 100 mg/kg 5-ALA reduced the concentration of inflammatory mediators associated with the pathogenesis of EIU. Furthermore, 5-ALA suppressed expression of inducible nitric oxide synthase in an in vitro study. In conclusion, 5-ALA suppressed inflammatory mediators and showed anti-inflammatory effects on EIU. 5-ALA needs further study because it may be an alternative to anti-inflammatory agents for treating uveitis. This study aimed to investigate the anti-inflammatory effect of 5-aminolevulinic acid (5-ALA) on endotoxin-induced uveitis (EIU) in rats. EIU was induced in male Sprague Dawley rats by the subcutaneous injection of lipopolysaccharide (LPS). During LPS injection, 5-ALA diluted with saline was administered via gastric gavage. After 24 h, clinical scores were assessed after which aqueous humor (AqH) samples were obtained. The number of infiltrating cells, protein concentration, and levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) in AqH were measured. For histological examination, both eyes of some rats were enucleated. In vitro, a mouse macrophage cell line (RAW264.7 cells) was stimulated by LPS with or without 5-ALA. Western blot was used to analyze the expression of inducible NO synthase (iNOS) and cyclooxygenase-2. 5-ALA suppressed the EIU clinical scores, infiltrating cell number, and protein concentration while improving the histopathologic scores. In particular, 100 mg/kg 5-ALA reduced the concentrations of NO, PGE2, TNF-α, and IL-6 in AqH, similar to 1 mg/kg prednisolone. In addition, 5-ALA suppressed iNOS upregulation in LPS-stimulated RAW264.7 cells. Therefore, 5-ALA has an anti-inflammatory effect on EIU through the inhibition of the upregulation of inflammatory mediators. [ABSTRACT FROM AUTHOR]

The metabolism of 5-aminolevulinic acid (ALA) is more efficient when combined with sodium ferrous citrate (SFC). Our previous study revealed that oral administration of ALA, which has anti-inflammatory properties, and SFC (ALA/SFC) immediately before lipopolysaccharide (LPS) inoculation suppressed endotoxin-induced uveitis (EIU) in rats. However, the therapeutic effect of ALA/SFC post-administration remains unexplored. Hence, this study aimed to evaluate the therapeutic efficacy of ALA/SFC on EIU in rats, which were administered with a gastric gavage of ALA/SFC (100/157 mg/kg) or prednisolone (Pred, 10 mg/kg) after 4 h of LPS inoculation. The treatment groups showed ameliorated clinical scores, inflammatory cells, protein levels in the aqueous humor (AqH), and histopathologic evaluation 24 h after LPS inoculation. Furthermore, the treatment groups had reduced tumor necrosis factor-α, nitric oxide, prostaglandin E2, and interleukin-6 levels in the AqH. ALA/SFC demonstrated an anti-inflammatory effect equivalent to that demonstrated by Pred. These findings indicate that ALA/SFC exerts a therapeutic effect on EIU in rats, indicating its clinical usefulness in uveitis treatment.

Exogenous ganglioside GM1 has been reported to exert an immunomodulatory effect. We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of lipopolysaccharide (LPS). GM1 was injected intraperitoneally for three consecutive days prior to the LPS injection. Twenty-four hours after the LPS injection, the integrity of the blood-aqueous barrier was evaluated by determining the protein concentration and number of infiltrating cells in the aqueous humor (AqH). Immunohistochemical and Western blot analyses of the iris-ciliary body (ICB) were performed to evaluate the effect of GM1 on the LPS-induced expression of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). The effect of GM1 on proinflammatory mediators and signaling cascades was examined in LPS-stimulated RAW 264.7 cells using Western blotting and immunofluorescence staining to further clarify the underlying anti-inflammatory mechanism. Results: GM1 significantly reduced the protein concentration and number of infiltrating cells in the AqH of rats with EIU. GM1 also decreased the LPS-induced expression of the ICAM-1 and COX-2 proteins in the ICB. In RAW 264.7 cells, GM1 inhibited the proinflammatory mediators induced by LPS, including inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and this inhibitory effect was potentially mediated by suppressing transforming growth factor-β-activated kinase 1 (TAK1) and reactive oxygen species (ROS)-mediated activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Conclusions: Based on this study, GM1 may be a potential anti-inflammatory agent for ocular inflammatory diseases. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the anti-inflammatory effect of 5-aminolevulinic acid (5-ALA) on endotoxin-induced uveitis (EIU) in rats. EIU was induced in male Sprague Dawley rats by the subcutaneous injection of lipopolysaccharide (LPS). During LPS injection, 5-ALA diluted with saline was administered via gastric gavage. After 24 h, clinical scores were assessed after which aqueous humor (AqH) samples were obtained. The number of infiltrating cells, protein concentration, and levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) in AqH were measured. For histological examination, both eyes of some rats were enucleated. In vitro, a mouse macrophage cell line (RAW264.7 cells) was stimulated by LPS with or without 5-ALA. Western blot was used to analyze the expression of inducible NO synthase (iNOS) and cyclooxygenase-2. 5-ALA suppressed the EIU clinical scores, infiltrating cell number, and protein concentration while improving the histopathologic scores. In particular, 100 mg/kg 5-ALA reduced the concentrations of NO, PGE2, TNF-α, and IL-6 in AqH, similar to 1 mg/kg prednisolone. In addition, 5-ALA suppressed iNOS upregulation in LPS-stimulated RAW264.7 cells. Therefore, 5-ALA has an anti-inflammatory effect on EIU through the inhibition of the upregulation of inflammatory mediators.

Purpose: To evaluate the anti-inflammatory effect of cortistatin (CST) in endotoxin-induced uveitis (EIU) model and to compare the results with corticosteroid treatment. Methods: A total of 35 healthy Wistar albino rats were randomly divided into five groups. EIU was induced by a single subcutaneous injection of lipopolysaccharide (LPS). Group I received intraperitoneal (ip) normal saline (NS), Group II received ip 150 μg LPS plus NS, Group III received ip 150 μg LPS plus 250 μg/kg CST, Group IV received ip 150 μg LPS plus 1mg/kg dexamethasone, and Group V received ip 250 μg/kg CST only. The aqueous humor was collected 24 h after injection and the infiltrating cells were determined. Moreover, histopathological and immunohistochemical examinations were also performed. Results: The clinical score and infiltrated cell count were reduced in Groups III and IV compared with Group II (P < 0.001). The pathological findings of Groups III and IV were significantly reduced compared with Group II (P < 0.001). These findings were similar between Groups III and IV (P = 1.000). Tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) immunoreactivity in the ciliary body of Group III and Group IV were significantly reduced compared with Group II (P < 0.001). TNF-α and IL-1β immunoreactivity in the ciliary body of Group III and Group IV were similar compared with Group I and Group V (range of P values was 0.539–0.958). Conclusion: CST administration as a therapeutic agent might ameliorate the severity of intraocular inflammation in uveitis patients. In conclusion, effect of CST and dexamethasone in EIU model was comparable.

To investigate protective effects of VVN001 on lipopolysaccharide (LPS)-induced inflammatory response in human retinal pigment epithelial (RPE) cells and in a mouse model of endotoxin-induced uveitis (EIU), and to explore the underlying mechanisms. Human primary RPE (hRPE) and ARPE-19 cells were pretreated with or without VVN001 for 1 h followed by 10 μg/mL LPS stimulation for 24 h. mRNA, and protein levels of inflammatory cytokines were analyzed with real-time PCR, western blotting, and ELISA. EIU was induced by intravitreal injection of 125 ng LPS in female BALB/c mice. VVN001 eye drops (1%) were locally administrated every 4 h for 24 h after LPS injection. Clinical scores were assessed with a slit lamp. mRNA and protein levels of inflammatory cytokines were investigated simultaneously. Compared with the LPS group, VVN001 pretreatment significantly reduced mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), IL-6, IL-8, TNF-α, IL-1β, IL-18, caspase-1 in hRPE, and ARPE-19 cells. Protein overproduction of ICAM-1, TNF-α, IL-1β, NLRP3, caspase-1 P20, and p-IκBα/IκBα stimulated by LPS was suppressed by VVN001 pretreatment. In vivo, VVN001 significantly reduced the average clinical score from 5.0 to 1.3 in EIU mice. Furthermore, overproduction of ICAM-1, IL-1β, NLRP3, caspase-1 P20, and p-IκBα/IκBα at mRNA and protein levels were remarkably suppressed by VVN001. VVN001 alleviated the inflammatory response induced by LPS both in vitro and in vivo. The effect of anti-inflammation is associated with inhibiting the overproduction of ICAM-1 and blocking the activation of NLRP3 inflammasome and the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Exogenous ganglioside GM1 has been reported to exert an immunomodulatory effect. We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of lipopolysaccharide (LPS). GM1 was injected intraperitoneally for three consecutive days prior to the LPS injection. Twenty-four hours after the LPS injection, the integrity of the blood-aqueous barrier was evaluated by determining the protein concentration and number of infiltrating cells in the aqueous humor (AqH). Immunohistochemical and Western blot analyses of the iris-ciliary body (ICB) were performed to evaluate the effect of GM1 on the LPS-induced expression of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). The effect of GM1 on proinflammatory mediators and signaling cascades was examined in LPS-stimulated RAW 264.7 cells using Western blotting and immunofluorescence staining to further clarify the underlying anti-inflammatory mechanism. Results: GM1 significantly reduced the protein concentration and number of infiltrating cells in the AqH of rats with EIU. GM1 also decreased the LPS-induced expression of the ICAM-1 and COX-2 proteins in the ICB. In RAW 264.7 cells, GM1 inhibited the proinflammatory mediators induced by LPS, including inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and this inhibitory effect was potentially mediated by suppressing reactive oxygen species (ROS)-mediated activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Conclusions: Based on this study, GM1 may be a potential anti-inflammatory agent for ocular inflammatory diseases.

αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases.

Purpose: Adiponectin has been shown to exert potent anti-inflammatory activities in a range of systemic inflammatory diseases. This study aimed to investigate the potential therapeutic effects of KS23, a globular adiponectin-derived peptide, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells.Methods: EIU was induced in Lewis rats by subcutaneous injection of LPS into a single footpad. KS23 or phosphate-buffered saline (PBS) was administered immediately after LPS induction via intravitreal injection. Twenty-four hours later, clinical and histopathological scores were evaluated, and the aqueous humor (AqH) was collected to determine the infiltrating cells, protein concentration, and levels of inflammatory cytokines. In vitro, cultured RAW 264.7 cells were stimulated with LPS in the presence or absence of KS23, inflammatory cytokine levels in the supernatant, nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65, and the expression of NF-kB signaling pathway components were analyzed.Results: KS23 treatment significantly ameliorated the clinical and histopathological scores of EIU rats and reduced the levels of infiltration cells, protein, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the aqueous humor. Consistently, KS23 decreased the expression of TNF-α and IL-6 in the supernatant of LPS-stimulated RAW 264.7 cells and inhibited the LPS-induced nuclear translocation of NF-κB p65 and the phosphorylation of IKKα/β/IκBα/NF-κB.Conclusion: The in vivo and in vitro results demonstrated the anti-inflammatory effects of the peptide KS23 and suggested that KS23 is a compelling, novel therapeutic candidate for the treatment of ocular inflammation.

αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: Lipocalin 2 (LCN2), an important mediator of a variety of cellular processes, is involved in regulating the inflammatory response, but its roles in different inflammatory diseases are controversial. Because the role of LCN2 in ocular inflammation has been unclear until now, we explored the function of LCN2 in lipopolysaccharide (LPS)-induced ocular inflammation in vivo and in vitro. Methods: Endotoxin-induced uveitis (EIU) was induced in male Sprague Dawley rats by the intravitreal injection of LPS. The expression and location of LCN2 in the retina were detected with western blotting and immunohistochemistry, respectively. We determined the clinical scores for anterior inflammation, quantified the infiltrated inflammatory cells, and measured the pro-inflammatory factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured primary rat Müller cells were stimulated with LPS and the expression and secretion of LCN2 were measured with real-time PCR, western blotting, and an ELISA. After Müller cells were cotreated with LPS and LCN2 or PBS, the expression and secretion of TNF-α, IL-6, and MCP-1 were examined with realtime PCR, western blotting, and ELISAs. Western blotting and immunofluorescence were used to detect the phosphorylation and cellular distribution of nuclear factor kappaB (NF-κB) subunit p65. Results: In EIU, the expression of LCN2 was significantly upregulated in the retina, especially in the outer nuclear layer (mainly composed of Müller cells). LPS stimulation of cultured Müller cells also markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly reduced the clinical scores, inflammatory infiltration, and protein leakage in EIU, which correlated with the reduced levels of proinflammatory factors in the aqueous humor and retina. LCN2 treatment also reduced the expression and secretion of TNF-α, IL-6, and MCP-1 in LPS-stimulated Müller cells. LCN2 inhibited the inflammatory response by inhibiting the phosphorylation and translocation of NF-κB p65. Conclusions: LCN2 protects against ocular inflammation, at least in part, by negatively regulating the activation of the NF-κB signaling pathway. LCN2 may be a promising anti-inflammatory therapy for ocular diseases, such as uveitis.

Background: Uveitis is an infrequent disease which constitutes a major cause of ocular morbidity. Correct management is essential, being corticosteroids its cornerstone. In case of contraindication to corticosteroids or treatment failure, the use of topical tacrolimus (TAC) could be an alternative which has already demonstrated safety and effectiveness in other ocular pathologies. However, TAC eye drops are not marketed, thus their elaboration must be carried out in Hospital Pharmacy Departments (HPDs). Methods: 32 Sprague-Dawley rats were divided into 4 groups of 8 rats each: (a) untreated healthy rats (Healthy); (b) untreated Endotoxin-Induced Uveitis model-rats (EIU); (c) EIU-rats treated with standard treatment of dexamethasone ophthalmic drops (DXM) and (d) EIU-rats treated with TAC-hydroxypropyl-β-cyclodextrin eye drops previously developed by our group (TAC-HPβCD). The mRNA expression levels of IL-6, IL-8, MIP-1α and TNF-α, quantitative analysis of leucocytes in aqueous humor and histological evaluation were performed. Results: TAC-HPβCD eye drops demonstrated to reduce ocular inflammation, expression of IL-6, TNF-α, MIP-1α and leukocyte infiltration in aqueous humor. Conclusions: TAC-HPβCD eye drops showed beneficial effect in EIU model in rats, positioning as an alternative for uveitis treatment in case of corticosteroids resistance or intolerance.

Purpose: To evaluate the anti-inflammatory effect of cortistatin (CST) in endotoxin-induced uveitis (EIU) model and to compare the results with corticosteroid treatment.Methods: A total of 35 healthy Wistar albino rats were randomly divided into five groups. EIU was induced by a single subcutaneous injection of lipopolysaccharide (LPS). Group I received intraperitoneal (ip) normal saline (NS), Group II received ip 150 μg LPS plus NS, Group III received ip 150 μg LPS plus 250 μg/kg CST, Group IV received ip 150 μg LPS plus 1mg/kg dexamethasone, and Group V received ip 250 μg/kg CST only. The aqueous humor was collected 24 h after injection and the infiltrating cells were determined. Moreover, histopathological and immunohistochemical examinations were also performed.Results: The clinical score and infiltrated cell count were reduced in Groups III and IV compared with Group II (P < 0.001). The pathological findings of Groups III and IV were significantly reduced compared with Group II (P < 0.001). These findings were similar between Groups III and IV (P = 1.000). Tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) immunoreactivity in the ciliary body of Group III and Group IV were significantly reduced compared with Group II (P < 0.001). TNF-α and IL-1β immunoreactivity in the ciliary body of Group III and Group IV were similar compared with Group I and Group V (range of P values was 0.539-0.958).Conclusion: CST administration as a therapeutic agent might ameliorate the severity of intraocular inflammation in uveitis patients. In conclusion, effect of CST and dexamethasone in EIU model was comparable. [ABSTRACT FROM AUTHOR]

Abstract Background Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet’s disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. Case presentation A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet’s disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Conclusions Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

Microglial cells are resident immune cells and play an important role in various cerebral and retinal inflammatory diseases. Notch1 signaling is involved in the microglia polarization and the control of cerebral inflammatory reactions. However, its role in endotoxin-induced uveitis (EIU) remains unknown. This study aimed to investigate the role of Notch1 signaling on retinal microglia polarization and inflammation in the cultured retinal microglial cells and EIU rat model. We found that Notch1 signaling blockade with N-[N-(3, 5-difluorophenacetyl)-1-alany1-S-phenyglycine t-butyl ester (DAPT) shifted retinal microglia phenotype from pro-inflammatory M1 phenotype (COX2+ and iNOS+) to anti-inflammatory M2 phenotype (Arg-1+) and reduced the release of pro-inflammatory cytokines both in vivo and in vitro. Moreover, DAPT treatment contributed to prevent retinal ganglion cells from apoptosis, reduce the intraocular infiltrating cells, and attenuate the impairment of retinal function. Taken together, these results suggest that inhibition of Notch1 signaling could alleviate the inflammatory response in EIU rat mainly through regulating the polarization of retinal microglia. Therefore, Notch1 signaling might be a promising therapeutic target in the treatment of ocular inflammatory diseases.

The aim of this study was to investigate the capability of polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles in improving the anti-inflammatory effects of dexamethasone (DEX). A film hydration method was used for the preparation of the DEX-loaded PCL-PEG-PCL micelles. In vitro cytotoxicity of the micelles obtained was investigated on L929 cells. Cellular uptake was studied by using flow cytometry and fluorescence microscopy. Anterior uveitis was induced in a group of rabbits by intravitreal injection of endotoxin from Salmonella typhimurium. The severity of inflammation-induced was clinically graded by using Hogan's classification method. Protein concentration in the aqueous humor was also measured. The micelles exhibited suitable compatibility on L929 cells and were taken up by the cells in a concentration- and time-dependent manner. The DEX-loaded micelles could reduce the clinical symptoms of uveitis after a lag-time. At 24 and 36 h after the LPS injection, the PCL-PEG-PCL micelles showed a better inhibitory effect on uveitis than the marketed eye drop, the differences did not reach significant levels though. This study demonstrated the potential of the PCL-PEG-PCL micelles as carriers for DEX in treating anterior uveitis. However, this concept is still to be further investigated. [ABSTRACT FROM AUTHOR]

Purpose: To investigate retinal gene expression of tetramethylpyrazine (TMP) eye drop-treated endotoxin-induced uveitis (EIU) in mice and to explore the mechanisms. Methods: The inflammatory signs of the anterior segment were evaluated, and clinical scores were graded. The retinal transcriptome from the TMP eye drop-treated and the untreated mice was identified by RNA sequencing (RNA-seq) strategy. Differentially expressed genes (DEGs) were validated by real-time PCR. The protein-protein interaction was analyzed using the STRING software. Results: Compared with the TMP-treated group, the inflammatory responses of the untreated control group were much severe and clinical score was remarkably higher (P < 0.001) at 24 h after lipopolysaccharide administration. RNA-seq assay identified 407 DEGs, among which 356 were upregulated and 51 were downregulated. There were 12 upregulated gene ontology terms enriched and 27 upregulated pathways. Seven DEGs, including inflammation-related, complement system-related, and interferon-related genes, were validated using quantitative PCR. Conclusions: TMP exerted anti-inflammatory effect in EIU. Local application of TMP inhibited retinal inflammatory response by regulating the inflammation-related genes, suggesting that TMP may be a potential novel therapeutic drug for ocular inflammation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the protective effect of LPS preconditioning against EIU in rats.Methods: EIU in Wistar rats was developed by subcutaneous injection of LPS (200 μg). Lower dose of LPS (0.1 mg/kg, intraperitoneally) or its carrier was injected daily for five days before EIU induction. Twenty-four hours after EIU, eyes were examined and then enucleated. The degree of inflammatory reaction was determined by routine histological examinations. Real-time RT-PCR and Western blot were used to determine the activation of NF-kB and expression of IRAK-1, IRAK-4, and IRAK-M Results: Repeated pre-administration of LPS induced a significant reduction in ocular inflammation and the expression of NF-κb p65 in neurons. The expression of IRAK-1 and IRAK-4 was suppressed in endotoxin tolerance group, whereas IRAK-M was increased.Conclusions: Endotoxin tolerance has a protective effect against EIU, and upregulation of IRAK-M through TLR-signaling pathway is one of the most likely candidates to be involved in the observed phenomenon. [ABSTRACT FROM AUTHOR]

Objective: This study was to evaluate the effect of systemic injection of an anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody (mAb) on endotoxin-induced uveitis (EIU). Materials and Methods: Fifty-six male Wistar rats (6–8 weeks old) were randomly divided into three groups: EIU, anti-TNF-α mAb + EIU, and control. EIU was induced by injecting Escherichia coli O55:B5 lipopolysaccharide (LPS) into the hind footpad of the rats (150 μg/rat). The anti-TNF-α mAb (1 μg/kg) was administrated 30 min before LPS injection through one-time intravenous injection. The onset time and peak time of EIU were recorded. The serum and aqueous humor (AH) TNF-α, interleukin (IL)-6, and IL-10 levels were measured by ELISA at 4, 24, and 72 h post-LPS injection. Clinical manifestations of EIU and eye histopathology were scored. Results: Compared with the EIU rats, anti-TNF-α mAb + EIU rats showed significantly delayed onset of uveitis (t = 7.41, P< 0.001), lower clinical scores and histopathological grades (t = 3.18/2.22, P< 0.001), reduced levels of TNF-α (F = 15.06/59.43, P< 0.001) and IL-6 (F = 99.63/14.92, P< 0.001), and increased levels of IL-10 (F = 24.94/8.99, P< 0.001) in the serum and AH. AH TNF-α, serum IL-6, and AH IL-6 levels are positively correlated, whereas serum IL-10 levels were negatively correlated with EIU activity. Conclusion: Antagonizing TNF-α by system injection of the anti-TNF-α mAb protects against EIU in rats. Blocking TNF-α signaling could be a useful strategy for managing uveitis.

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism.Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated.Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role.Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.

The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53), on the ocular inflammation of experimental endotoxin-induced uveitis (EIU) and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKβ, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases.

Retinoblastoma is the prototypic genetic cancer. India carries the biggest burden of retinoblastoma globally, with an estimated 1500 new cases annually. Recent advances in retinoblastoma genetics are reviewed, focusing specifically on information with clinical significance to patients. The Indian literature on retinoblastoma clinical genetics is also highlighted, with a comment on challenges and future directions. The review concludes with recommendations to help clinicians implement and translate retinoblastoma genetics to their practice.

Purpose: The purpose was to evaluate choroidal thickness via spectral domain optical coherence tomography (SD-OCT) and to compare the data with those of 24-h blood pressure monitoring, elastic features of the aorta, and left ventricle systolic functions, in patients with systemic hypertension. Materials and Methods: This was a case-control, cross-sectional prospective study. A total of 116 patients with systemic hypertension, and 116 healthy controls over 45 years of age, were included. Subfoveal choroidal thickness (SFCT) was measured using a Heidelberg SD-OCT platform operating in the enhanced depth imaging mode. Patients were also subjected to 24-h ambulatory blood pressure monitoring (ABPM) and standard transthoracic echocardiography (STTE). Patients were divided into dippers and nondippers using ABPM data and those with or without left ventricular hypertrophy (LVH+ and LVH-) based on STTE data. The elastic parameters of the aorta, thus aortic strain (AoS), the beta index (BI), aortic distensibility (AoD), and the left ventricular mass index (LVMI), were calculated from STTE data. Results: No significant difference in SFCT was evident between patients and controls (P ≤ 0.611). However, a significant negative correlation was evident between age and SFCT in both groups (r = −0.66/−0.56, P ≤ 0.00). No significant SFCT difference was evident between the dipper and nondipper groups (P ≤ 0.67), or the LVH (+) and LVH (-) groups (P ≤ 0.84). No significant correlation was evident between SFCT and any of AoS, BI, AoD, or LVMI. Discussion : The choroid is affected by atrophic changes associated with aging. Even in the presence of comorbid risk factors including LVH and arterial stiffness, systemic hypertension did not affect SFCT.

Purpose: The effect of hypothyroidism on the choroidal thickness (CT) was investigated in patients with subclinical hypothyroidism and overt hypothyroidism, and biochemically and clinically euthyroid patients receiving levothyroxine treatment. The patients were compared with healthy subjects. Materials and Methods: One eye of 71 hypothyroid and 22 healthy subjects between 20 and 40 years of age were included in this study. CT measurements were taken at the fovea and at 2 points that were 1500 μm nasal and temporal to the fovea using spectral-domain optical coherence tomography. Independent sample t-test′s and was used for statistical analysis of the data. Results: The CT was significantly thicker in hypothyroid patients compared to healthy subjects (P values were 0.013 for subfoveal, 0.015 for temporal and 0.020 for nasal segments). The intraocular pressure (IOP) and body mass index (BMI) were also significantly higher in hypothyroid patients (P values were 0.021 and 0.003, respectively). There was not a statistically significant difference in the BMI and IOP measurements between healthy subjects and euthyroid patients (P > 0.05). However, there was a statistically significant difference in the subfoveal, temporal and nasal CT measurements between healthy subjects and euthyroid patients (P values were 0.006, 0.031 and 0.013, respectively). Conclusions: All subgroups of hypothyroid patients had thicker CT compared to healthy subjects. Euthyroid patients receiving levothyroxine treatment had lower IOP, BMI levels, and serum lipid levels than patients with subclinical hypothyroidism and overt hypothyroidism.

An 18-year-old Indian girl with upper lip deformity presented with on and off painless swelling of her both upper eyelids for 3 years. Clinical evaluation revealed bilateral blepharochalasis, narrowing of horizontal palpebral fissure, decreased outer intercanthal distance, iris coloboma, cleft soft palate, bifid uvula, sensorineural deafness and double upper lip. Clinical examination of the thyroid, thyroid hormone assay and ultrasonography revealed normal thyroid gland structure and function. Ascher′s syndrome was diagnosed. To our knowledge, this is the first reported case of Ascher′s syndrome associated with iris coloboma, heterochromia iridum, and narrowing of horizontal palpebral fissure and decreased outer intercanthal distance secondary to lengthening of lateral canthal ligament.

Aim: The intraocular silicone oil (SO) tamponades used in the treatment of retinal detachment (RD) have been associated with a difference ocular hypertension (OH) rate. To clarify, if this complication was associated to use of standard SO (SSO) versus heavy SO (HSO), we performed a systematic review and meta-analysis of comparative study between two kind of SO (standard or light vs. heavy) for the treatment of RD and macular hole, without restriction to study design. Materials and Methods: The methodological quality of two randomized clinical trials (RCTs) were evaluated using the criteria given in the Cochrane Handbook for Systematic Reviews of Intervention, while three non-RCTs were assessed with the Newcastle-Ottawa Scale and Strengthening the Reporting of Observational Studies in Epidemiology checklists. We calculated Mantel-Haenszel risk ratio (RR) with 95% confidence intervals (95% CIs). The primary outcome was the rate of patients with OH treated with SSO compared to HSO. Results: There were a higher number of rates of OH in HSO compared to SSO. This difference was statistically significant with the fixed effect model (Mantel-Haenszel RR; 1.55; 95% CI, 1.06-2.28; P = 0.02) while there was not significative difference with the random effect model (Mantel-Haenszel RR; 1.51; 95% CI, 0.98-2.33; P = 0.06). Conclusion: We noted a trend that points out a higher OH rate in HSO group compared to SSO, but this finding, due to the small size and variable design of studies, needs to be confirmed in well-designed and large size RCTs.

Over the past several decades, animal models of autoimmune uveitis directed at eye-specific antigens (Ags) have been developed. These have allowed researchers to understand the basic mechanisms that lead to these diseases and also recently helped the researchers in translational research for therapeutic interventions. Experimental autoimmune uveitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal Ags. Ever since the first description of EAU in mice in 1988, several animal models of uveitis has been described by researchers. Disease-specific model for cytomegalovirus retinitis and tubercular uveitis has evolved our understanding of these complex entities. Endotoxin induced uveitis is another useful model for anterior uveitis, which is not an autoimmune process and is triggered by injection of bacterial endotoxin (lipopolysaccharides) resulting in a rapid short lasting uveitis. The current article will give an insight into the various EAU animal models and their current implications in translational research. The article will also highlight the different grading systems for EAU in the animal model.

Background/Aims: Information on eye diseases in blind school children in Allahabad is rare and sketchy. A cross-sectional study was performed to identify causes of blindness (BL) in blind school children with an aim to gather information on ocular morbidity in the blind schools in Allahabad and in its vicinity. Study Design and Setting: A cross-sectional study was carried out in all the four blind schools in Allahabad and its vicinity. Materials and Methods: The students in the blind schools visited were included in the study and informed consents from parents were obtained. Relevant ocular history and basic ocular examinations were carried out on the students of the blind schools. Results: A total of 90 students were examined in four schools of the blind in Allahabad and in the vicinity. The main causes of severe visual impairment and BL in the better eye of students were microphthalmos (34.44%), corneal scar (22.23%), anophthalmos (14.45%), pseudophakia (6.67%), optic nerve atrophy (6.67%), buphthalmos/glaucoma (3.33%), cryptophthalmos (2.22%), staphyloma (2.22%), cataract (2.22%), retinal dystrophy (2.22%), aphakia (1.11%), coloboma (1.11%), retinal detachment (1.11%), etc. Of these, 22 (24.44%) students had preventable causes of BL and another 12 (13.33%) students had treatable causes of BL. Conclusion: It was found that hereditary diseases, corneal scar, glaucoma and cataract were the prominent causes of BL among the students of blind schools. Almost 38% of the students had preventable or treatable causes, indicating the need of genetical counseling and focused intervention.

Introduction: Superior oblique split lengthening (SOSL) is done for weakening of superior oblique. It corrects the superior oblique overaction (SOOA) and A pattern. Its effect on the torsion of the eye is not known. We present our data on the effect of this particular procedure on torsion. Materials and Methods: We did a study of 16 patients (32 eyes) who underwent bilateral SOSL and compared the disc foveal angle (DFA) preoperatively and postoperatively. The split lengthening was done from 4 mm to 7 mm depending upon the overaction of superior oblique. Results: The mean age was 15.3 ± 8.4 years. Mean preoperative DFA in the right eye (RE) was −3.9° and in the left eye (LE) was −2.9°. Mean postoperative DFA in RE was 0.2° and in LE was 0.9°. The mean change in the DFA for RE was 4.1° ± 1.3° and for LE was 3.8° ± 1.2°. All the patients were aligned horizontally within 6 prism diopter and no pattern and no diplopia postoperatively. The A pattern was corrected in all the patient postsurgery. For each mm of surgery, an improvement of 0.8° was seen in the DFA. Conclusion: We report the effect of SOSL on torsion. The SOSL reduces intorsion postsurgery and is, therefore, a valuable procedure in SOOA where both pattern and in torsion needs to be corrected.

Context: This study was carried out as a part of an internal audit and is the largest series of patients having keratoglobus, published in the literature. Poor visual acuity of the patients indicates the blinding nature of the disease. Aims: We report our experience with patients having keratoglobus at a tertiary eye care center in India. Settings and Design : Retrospective study. Materials and Methods: We analyzed adults and pediatric patients (20/40 in 6/42 (14.3%) pediatric eyes and 15/53 (28.30%) adults. Visual acuity ranging from counting of fingers to no light perception was noted in 20/53 (37.74%) adults and 21/42 (50%) pediatric patients; 13/20 (65%) with blue sclera and 8/22 eyes (36.37%) without blue sclera. Vernal keratoconjunctivitis was present in one pediatric patient. Choroidal osteoma, retinitis pigmentosa, and retinal detachment were present in adults. Surgeries performed were corneal tear repair (5 eyes), tissue adhesive application (2 eyes), descematopexy (4 eyes) and penetrating keratoplasty (PK - 8 eyes: Three had post-PK glaucoma, graft failure-one eye, 4 patients wore scleral lens - prosthetic replacement of the ocular surface ecosystem). Conclusions: About 50% of pediatric eyes (65% having blue sclera) had no functional vision. Trivial trauma was responsible for corneal rupture indicating need for protective glasses. About 50% patients had post-PK glaucoma though grafts were clear.

Purpose: To evaluate the anti-inflammatory effect of lithium chloride in endotoxin-induced uveitis.Methods: A total of 200 Wistar rats were randomly divided into four groups: a control group; EIU group; LiCl-treated control group; and LiCl-treated lipopolysaccharide group. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining were used to determine the degree of inflammatory reaction. Level of glycogen synthase kinase3-beta and nuclear factor-kappa B p65 in iris-ciliary body was examined by western blot and RT-PCR. Cytokines in aqueous humor were detected by ELISA.Results: Pretreatment with LiCl produced an anti-inflammatory effect during endotoxin-induced uveitis (EIU). With LiCl treatment, the level of P-GSK3-β in iris-ciliary body was upregulated and the expression of NF-κB p65 was significantly suppressed during EIU.Conclusions: LiCl pretreatment can suppress intraocular inflammatory responses in EIU rats. Mechanistically, this anti-inflammatory effect may be related to the inhibitory phosphorylation of GSK3-β. [ABSTRACT FROM AUTHOR]

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the clinical and histopathological effects of intravitreal injection of pentoxifylline (PTX) the management of an experimental model of uveitis. Fifty-two rabbits were divided randomly into six intravitreal treated groups as below: 1) Balanced salt solution (BSS), 2) Salmonella typhimurium lipopolysaccharide endotoxin (LPS) + BSS, 3) LPS + PTX 100 μg, 4) LPS + PTX 500 μg, 5) BSS + PTX 100 μg and 6) BSS + PTX 500 μg. Inflammation was evaluated by clinical examinations using slit lamp on days 1, 3, 5 and 7 post injections and histopathological examinations were also performed at the end of the study. Clinical examinations demonstrated a statistically significant difference between group 1 and group 2 on day 5 and day 7. Moreover, the comparison of clinical severity scores of group 1 with groups 3, 4, 5 and 6, on third, fifth and seventh post-injection days showed statistically significant differences. The mean histopathological inflammation intensity score in groups 5 and 6 was significantly higher than group 1. The mean histopathological inflammation intensity score in groups 3, 4, 5 and 6 was significantly higher than group 2. Intravitreal injection of PTX in an experimental model of uveitis in rabbits not only does not reduce inflammation but also leads to inflammation when used alone or in combination with LPS. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53), on the ocular inflammation of experimental endotoxininduced uveitis (EIU) and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKβ, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: Lipocalin 2 (LCN2), an important mediator of a variety of cellular processes, is involved in regulating the inflammatory response, but its roles in different inflammatory diseases are controversial. Because the role of LCN2 in ocular inflammation has been unclear until now, we explored the function of LCN2 in lipopolysaccharide (LPS)-induced ocular inflammation in vivo and in vitro. Methods: Endotoxin-induced uveitis (EIU) was induced in male Sprague Dawley rats by the intravitreal injection of LPS. The expression and location of LCN2 in the retina were detected with western blotting and immunohistochemistry, respectively. We determined the clinical scores for anterior inflammation, quantified the infiltrated inflammatory cells, and measured the pro-inflammatory factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured primary rat Müller cells were stimulated with LPS and the expression and secretion of LCN2 were measured with real-time PCR, western blotting, and an ELISA. After Müller cells were cotreated with LPS and LCN2 or PBS, the expression and secretion of TNF-α, IL-6, and MCP-1 were examined with realtime PCR, western blotting, and ELISAs. Western blotting and immunofluorescence were used to detect the phosphorylation and cellular distribution of nuclear factor kappaB (NF-κB) subunit p65. Results: In EIU, the expression of LCN2 was significantly upregulated in the retina, especially in the outer nuclear layer (mainly composed of Müller cells). LPS stimulation of cultured Müller cells also markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly reduced the clinical scores, inflammatory infiltration, and protein leakage in EIU, which correlated with the reduced levels of proinflammatory factors in the aqueous humor and retina. LCN2 treatment also reduced the expression and secretion of TNF-α, IL-6, and MCP-1 in LPS-stimulated Müller cells. LCN2 inhibited the inflammatory response by inhibiting the phosphorylation and translocation of NF-κB p65. Conclusions: LCN2 protects against ocular inflammation, at least in part, by negatively regulating the activation of the NF-κB signaling pathway. LCN2 may be a promising anti-inflammatory therapy for ocular diseases, such as uveitis. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced leucine zipper (GILZ) mediates several effects of glucocorticoids and has important anti-inflammatory properties. Here, we explored the role of GILZ in inhibiting retinal inflammation. Endotoxin-induced uveitis (EIU) was established in rats by intravitreal injection of lipopolysaccharide (LPS). GILZ levels decreased in the EIU retina after LPS injection. Retinal GILZ was downregulated by recombinant lentivirus-delivered short-hairpin RNA targeting GILZ (shRNA-GILZ-rLV) and upregulated by recombinant lentivirus-mediated GILZ overexpression (Oe-GILZ-rLV). GILZ silencing attenuated the anti-inflammatory effects of intravitreal injection of triamcinolone acetonide (TA) in the EIU retina, as demonstrated by increased retinal interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1and intercellular cell adhesion molecule-1 expression at 18 h after TA injection. A Bio-Plex cytokine assay and western blotting demonstrated that GILZ overexpression inhibited the effects of LPS, downregulating retinal IL-1β, MCP-1, MIP-1α, and IL-17 and inhibiting LPS-induced activation of the retinal toll-like receptor 4–myeloid differentiation factor 88 signaling pathway. At 48 and 72 h after LPS injection, the clinical score of inflammation was significantly lower in Oe-GILZ-rLV–transfected eyes than in blank-rLV–transfected eyes. Histological examination showed a 67.85% reduction of infiltrating inflammatory cells in the anterior chamber and a 58.97% reduction in vitreous cavity of Oe-GILZ-rLV transfected eyes at 48 h after LPS injection. Taken together, our results suggest that GILZ is a novel therapeutic target for the treatment of retinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Dislocation of intraocular lens (IOL) is a serious complication of blunt ocular trauma in pseudophakic eyes. Here, a 72-year-old male patient with subconjunctival dislocation of an IOL (pseudophacocele) secondary to bull horn injury was reported. In this case report, a new sign named as "golden half ring sign" was described for easy identification and localization of subconjunctival dislocation of IOL in patient with open globe injury (surgical wound dehiscence) associated dense subconjunctival hemorrhage.

Fibromas are benign tumors that are composed of fibrous or connective tissue. They can grow in all organs, arising from mesenchymal tissue (a type of loose connective tissue). The term "fibroblastic" or "fibromatous" is used to describe tumors like the fibroma. This 69-year-old male presented to us with giant, multiple, very slowly progressive, painless, noninflammatory, soft, trans-illuminant, pedunculated lid swellings with a two decade history. There were no other swellings on the body. He was clinically normal on systemic examination except for the immature cataracts in both eyes. The diagnosis was confirmed on histopathology. Simple excision removed all the soft fibromas virtually leaving no scar. A review of literature world-wide using Medline Plus/PubMed revealed this to be the only reported case of multiple giant soft fibromas of the lid.

Spontaneous intraocular lens (IOL) dislocation is uncommon in the absence of any ocular areas with zonular weakness or trauma. There have been no reports of spontaneous capsular bag dislocation into the anterior chamber without an IOL. We report a rare, interesting case of spontaneous capsular bag anterior dislocation, without an IOL, into the anterior chamber with no history of genetic disease, ocular trauma, or pseudoexfoliation that might predispose to a zonular abnormality.

Pyomyositis is a primary bacterial infection of striated muscles nearly always caused by Staphylococcus aureus. Development of the intramuscular abscess involving the extra-ocular muscles (EOMs) remains an extremely rare process. We herein present a case of isolated EOM pyomyositis involving superior rectus muscle in a 2-year male child who was referred with complaints of swelling in left eye (LE) and inability to open LE since last 1-month. Orbital computed tomography (CT) scan showed a well-defined, hypo-dense, peripheral rim-enhancing lesion in relation to left superior rectus muscle suggestive of left superior rectus abscess. The abscess was drained through skin approach. We concluded that pyomyositis of EOM should be considered in any patient presenting with acute onset of orbital inflammation and characteristic CT or magnetic resonance imaging features. Management consists of incision and drainage coupled with antibiotic therapy.

A relatively simple and inexpensive technique to train surgeons in phacoemulsification using a goat′s eye integrated with a human cataractous nucleus is described. The goat′s eye is placed on a bed of cotton within the lumen of a cylindrical container. This is then mounted on a rectangular thermocol so that the limbus is presented at the surgical field. After making a clear corneal entry with a keratome, the trainer makes a 5-5.5 mm continuous curvilinear capsulorhexis in the anterior lens capsule, creates a crater of adequate depth in the cortex and inserts the human nucleus within this crater in the goat′s capsular bag. The surgical wound is sutured, and the goat′s eye is ready for training. Creating the capsulorhexis with precision and making the crater of adequate depth to snugly accommodate the human nucleus are the most important steps to prevent excessive wobbling of the nucleus while training.