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Background: To explore the changes of gut microbiota in Graves' orbitopathy (GO) patients of different severity grades and to identify the pathogenic bacteria of GO and the associated mechanism. Methods: A total of 18 healthy controls and 62 GO patients were recruited. The baseline information and faecal samples of all subjects were collected for gut microbiota analysis and metabolic function prediction analysis. 16SrDNA sequencing was used for microbial diversity detection. The operational taxonomic unit (OTU) was divided using the Mothur software, and the dominant microbiota was analysed. OTU number, Chao1 index, ACE index, and Shannon index of microbiota in faecal samples were analysed using the QIIME1.9.0 software. The relative abundance of microbiota in faecal samples was analysed through principal component analysis (PCA) using the Canoco Software 5.0. The metabolic function of microbiota in faecal samples was predicted using PICRUSt 2.0. Results: There was no remarkable difference in gut microbiota diversity between groups; however, the gut microbial community and dominant microbiota significantly differed among groups. Klebsiella_pneumoniae was deemed the potentially pathogenic bacteria of GO, and its abundance was positively correlated with disease severity. The metabolic prediction results revealed that inorganic nutrition metabolism, fatty acid and lipid degradation, electron transfer, aromatic compound degradation, and alcohol degradation were notably different between groups with high and low abundance of Klebsiella_pneumoniae and among groups with different GO severity grades, thereby showing a positive correlation with GO clinical risks. Conclusions: Klebsiella_pneumoniae was a potential GO‐related pathogen, which may regulate the metabolic pathways to affect GO progression. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence has indicated that the entire visual pathway from retina to visual cortex may be involved in dysthyroid optic neuropathy (DON) pathological mechanisms. Purpose: To explore the functional and morphological brain characteristics in DON and their relationship with ophthalmologic performance. Study Type: Retrospective. Population: A total of 30 DON patients, 40 thyroid‐associated ophthalmopathy (TAO) without DON patients and 21 healthy‐controls (HCs). Field Strength/Sequence: A 3.0 T, 3D T1‐weighted spoiled gradient‐recalled echo and gradient‐recalled echo‐planar imaging. Assessment: Functional and structural alterations in brain regions were evaluated with fractional amplitude of low‐frequency fluctuations, degree centrality (DC), and gray matter volume (GMV). Clinical activity score (CAS) is assessed across patients. Statistical Test: One‐way analysis of variance with post hoc two sample t‐tests (GRF‐corrected, voxel level: P < 0.005, cluster level: P < 0.05) and correlation analysis (significance level: P < 0.05). Results: Compared to HCs, DON patients had significantly decreased DC values in the bilateral BA17 and BA18 regions. Compared to the TAO group, DON patients had decreased GMV in the left anterior cingulate cortex, left middle frontal gyrus, left lingual gyrus, left parietal gyrus, right Rolandic operculum, left supplementary motor area, and right middle temporal gyrus. In addition, GMV in the right Rolandic operculum was significantly positively correlated with CAS (correlation coefficient: r = 0.448). Data Conclusion: This study showed significant morphological and functional alterations in visual cortex and morphological alterations in partial default mode network regions of DON patients, which may provide insights into the mechanism of vision loss and may facilitate the diagnosis and treatment of DON. Evidence Level: 3. Technical Efficacy: Stage 3. [ABSTRACT FROM AUTHOR]

• It is the first clinical report of Nectria haematococca infection in humans. • N. haematococca keratitis is severe and likely to recur after keratoplasty. • The recurrence occurred primarily in the second week after keratoplasty. • The effect of local use of fluconazole and voriconazole is not ideal. • The next-generation sequencing is useful in the diagnosis of rare fungal infections. Fungal keratitis (FK) is a kind of serious corneal infection and penetrating keratoplasty (PKP) is needed when medical therapy fails. Although Nectria haematococca is found as endophytes in the roots of some plant species, there has been no report of N. haematococca infection in human. We reviewed 46 patients who underwent PKP due to FK in our hospital from July 2021 to December 2021, and there were three patients who had relapsed. The next-generation sequencing revealed that all three corneas were infected with N. haematococca. Based on the ocular manifestation and treatment course of three cases, we summarize the characteristics of N. haematococca FK: the scope of corneal infection was widespread with severe hypopyon. The effect of local use of fluconazole and voriconazole was not ideal, and PKP was the main treatment. Even after a large-scale corneal lesion resection, the lesion may recur. The recurrence occurred primarily in the second week after PKP. This is the first clinical report of N. haematococca infection in humans. Compared with the other currently known FK caused by the Fusarium solani species complex, N. haematococca keratitis is more severe and more likely to recur. [ABSTRACT FROM AUTHOR]

Background: The mechanism driving dysthyroid optic neuropathy (DON) is unclear. Diffusion‐tensor imaging (DTI) allows for noninvasively assessing the microstructure of the entire visual pathway and may facilitate a better understanding of the mechanism of DON. Purpose: To assess microstructural changes of the whole visual pathway and to investigate the potential mechanism of trans‐synaptic damage（TSD） pathogenesis in DON with DTI. Study Type: Cross‐sectional. Population: Sixty‐four patients with bilateral thyroid‐associated ophthalmopathy (TAO), 30 with and 34 without DON, and 30 age‐ and sex‐matched healthy controls (HCs). Field Strength/Sequence: 3 T/DTI (A single‐shot diffusion‐weighted echo‐planar imaging sequence). Assessment: Differences in DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in each segment (optic nerve, tract, and radiation) of the entire visual pathway among the groups were compared. The parameters of visual evoked potentials (VEPs), visual field tests, and mean retinal nerve fiber layer (mRNFL) thickness on optical coherence tomography were also compared across patients. Statistical Tests: Student's t‐test, chi‐square test; ANOVA with post‐hoc testing, interclass correlation coefficient, and correlation analysis. Significance level: P < 0.05. Results: TAO patients with DON showed significantly reduced mRNFL thickness and abnormal VEPs. There was a tendency for gradually reduced FA and AD, and increased RD and MD from HCs, with non‐DON to with DON in optic nerve and tract, statistically. For radiation, the RD and MD showed statistical increase, the AD and FA just showed numerical decrease (P = 0.119 and 0.059, respectively). For DON, the FA and MD of visual pathway segments showed correlations with abnormal VEPs. Data Conclusion: DTI may be a useful tool for detecting microstructural changes in the entire visual pathway in DON. The changes in RNFL thickness and DTI parameters suggested TSD as a potential pathogenic mechanism of DON. Evidence Level: 4 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Background: The correlation between intraocular pressure (IOP) and the magnetic resonance imaging (MRI) parameters in thyroid-associated ophthalmopathy (TAO) patients was explored. Methods: This study included 82 eyes in 41 TAO patients who had a large difference in the IOP between each eye. We measured the T2 relaxation time (T2RT) of the extraocular muscles (EOMs), the orbital fat, and the area of the EOMs. Results: There was a positive correlation between IOP and exophthalmos, the clinical activity score (CAS), the T2RT (of the medial rectus (MR)), the area of the MR, inferior rectus (IR) and lateral rectus, and the mean area. We established a regression model with IOP as the dependent variable, and the area of the IR was statistically significant. Conclusions: High IOP in TAO patients was positively correlated with the degree of exophthalmos and EOM inflammation (especially the inferior rectus). The state of the EOMs in an orbital MRI may partially explain high IOP and provide the necessary clinical information for subsequent high IOP treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the microstructural changes of the orbital optic nerve in thyroid-associated ophthalmopathy (TAO) patients with or without dysthyroid optic neuropathy (DON) using diffusion tensor imaging (DTI) and investigate whether DTI can be used to detect DON. Materials and Methods: 59 bilateral TAO patients with (n= 23) and without DON (non-DON, n= 36) who underwent pretreatment DTI were included and 118 orbits were analyzed. The clinical features of all patients were collected. DTI parameters, including mean, axial, and radial diffusivity (MD, AD, and RD, respectively) and fractional anisotropy (FA) of the intra-orbital optic nerve for each orbit were calculated and compared between the DON and non-DON groups. ROC curves were generated to evaluate the diagnostic performance of single or combined DTI parameters. Correlations between DTI parameters and ophthalmological characteristics were analyzed using correlation analysis. Results: Compared with non-DON, the DON group showed decreased FA and increased MD, RD, and AD (P < 0.01). In the differentiation of DON from non-DON, the MD was optimal individually, and the combination of the four parameters had the best diagnostic performance. There were significant correlations between the optic nerve's four DTI metrics and the visual acuity and clinical active score (P < 0.05). In addition, optic nerve FA was significantly associated with the amplitude of visual evoked potentials (P = 0.022). Conclusions: DTI is a promising technique in assessing microstructural changes of optic nerve in patients with DON, and it facilitates differentiation of DON from non-DON eyes in patients with TAO. [ABSTRACT FROM AUTHOR]

To investigate the association between serum immunoglobulin G4 (IgG4) levels and laboratorial parameters. Moreover, the ocular manifestations were compared in Graves' ophthalmopathy (GO) patients. Fifty-seven GO patients and fifty sex- and age-matched euthyroid subjects were enrolled. Serum IgG4 and immunoglobulin G (IgG) levels, thyroid hormones and thyroid autoantibodies were measured in all participants. Ophthalmologic examinations were performed to GO patients. Serum IgG4 levels were increased in GO patients compared with euthyroid subjects (p<0.001). Multivariate analysis showed that TRAb levels were correlated with IgG4 levels in GO patients (β=1.45, p = 0.024). There were eight GO patients with IgG4 levels ≥ 135 mg/dL. They all had both eyelids swelling and the differences of HER were less than 2mm. Seven patients (7/8) showed bilateral symmetrical thickening of the extraocular muscles. Bilateral symmetry of ocular manifestation was observed in GO patients with IgG4 levels ≥135 mg/dL. IgG4 levels may be helpful in monitoring GO and diagnosing a new subtype of GO. [ABSTRACT FROM AUTHOR]

Purpose: (1) To measure the corneal endothelium-Descemet membrane (EDM) layer thickness in Descemet membrane detachment (DMD) patients in vivo using high-definition optical coherence tomography (HD-OCT), and to investigate its correlation with age. (2) To explore whether the detachment time will affect the EDM thickness. (3) To explore whether the EDM thickness of cornea with DMD was different from that without DMD. Participants: Patients with DMD were divided into three groups. Group 1 included twenty-three patients whose Descemet membrane (DM) was partial or complete detached from the corneal stroma after various ocular surgeries. Group 2 included eight patients from group 1 who underwent twice HD-OCT examination on different days before the DM reattached to the stroma. Group 3 included nine patients from group 1 who had clear grayscale boundary between the DM and stroma in HD-OCT images after DM reattachment. Methods: All patients underwent HD-OCT and EDM thickness was measured using Image -Pro Plus 6.0. In Group 1, regression analyses were used to evaluate the correlation between EDM thickness and age, and the thickness difference between the ≤50-year-old group and the >50-year-old group was analyzed by independent sample t-test. In Group 2, paired samples t-test was used to check whether detachment time would affect EDM thickness. In Group 3, paired samples t-test was used to check whether the EDM thickness of cornea with DMD was different from that without DMD. p < 0.05 was considered significant. Results: In Group 1, the EDM thickness measured on the first post-operative day was 27.8 ± 3.6 μm, and a positive correlation was found between EDM thickness and age (r = 0.619, p < 0.05). The EDM thickness of ≤50-year-old group and >50-year-old group were 23.9 ± 3.2 and 29.2 ± 2.6 μm, and there was a significant difference between the two groups (p = 0.001). In Group 2, the first measurement of EDM thickness was 27.5 ± 4.0 μm, the second measurement was 27.6 ± 4.2 μm, the interval between the two measurements was 2.1 ± 1.6 days, and there was no significant difference between the two measurements (p = 0.328). In Group 3, the EDM thickness with DM detachment was 28.3 ± 3.5 μm, with DM reattachment was 23.4 ± 2.4 μm, there was a significant difference between the two measurements (p = 0.002). Conclusions: The EDM thickness in the state of DMD is thicker than its actual thickness in normal cornea, and EDM thickness of the >50-year-old group is much thicker than that of the ≤50-year-old group. [ABSTRACT FROM AUTHOR]

Lacrimal canaliculitis (LC) is a rare infection of lacrimal passage, which is usually late diagnosed or misdiagnosed. Traditional lacrimal system tests barely provide a clear and definite understanding of the pathological changes in lacrimal passage. We presented three patients with asymptomatic and atypical symptoms who were misdiagnosed and were eventually diagnosed with chronic LC with assistance of 80‐MHz ultrasound biomicroscopy (80‐MHz UBM) and lacrimal endoscopy. To our knowledge, the mutual assistance of above two techniques diagnosing LC has never been reported, it can provide better images and observations of the canaliculus from the inside out and can guide the differential diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Previous study suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The aims of the present study were to investigate the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients. Design: 69 GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. Furthermore, the clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, intraocular pressure, diplopia and lid width) after high‐dose intravenous GC treatment in 32 active moderate‐to‐severe GO patients were compared. Patients: 69 consecutive patients with GO were asked to participate in the study. 32 of 69 GO patients were treated with high‐dose intravenous GCs. Measurements: Measurement of serum IgG and IgG4, serum thyroid hormones and thyroid autoantibodies. An overall ophthalmic assessment was performed pretherapy (week 0) and post‐therapy (week 12). Results: 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels were positively correlated with the severity and activity of GO. After GC therapy, IgG4, IgG4/IgG, vision and CAS were significantly improved in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels. Conclusions: Our results suggest a possible subgroup of elevated IgG4 GO patients, with more severe ophthalmopathy and better response to GCs treatment compare with normal IgG4 GO patients. [ABSTRACT FROM AUTHOR]

Background: With the extensive development of endoscopic sinus surgery, iatrogenic medial rectus muscle injury should be treated with caution. Traditional methods to repair a ruptured medial rectus need an anterior orbitotomy approach, with more injury and difficulty in finding the posterior end of the ruptured medial rectus. Objective: To explore a new method to repair a ruptured medial rectus. Methods: Eight cases of iatrogenic medial rectus rupture after endoscopic sinus surgery were reviewed from July 2015 to January 2019. Assisted by image-guided navigation, the ruptured medial rectus was sutured under an endoscopic endonasal orbital approach. Two methods were designed to suture the ruptured medial rectus. Optic nerve and orbital decompression were performed in 5 cases with visual impairment. The extent of exotropia and diplopia were followed up for 5 to 33 months after surgery. Results: With the help of image guidance, the posterior and anterior ends of the ruptured medial rectus of all patients were pinpointed, and operations using medial rectus anastomosis were successfully completed in 7 patients. The exotropia of these patients was corrected, and they have recovered. The vision of 2 patients recovered. There were no minor or major complications intraoperatively or postoperatively. Conclusion: Assisted by image-guided navigation, medial rectus anastomosis under an endoscopic endonasal orbital approach is a feasible method. The key to preventing orbital complications is strict professional training, including identification of the Onodi air cell and correct application of powered instrumentation. [ABSTRACT FROM AUTHOR]

Objective: Prediction of therapy response to intravenous methylprednisolone pulses (ivMP) is crucial for thyroid-associated ophthalmopathy (TAO). Image histograms may offer sensitive imaging biomarkers for therapy effect prediction. This study aimed to investigate whether pretherapeutic, multiparametric T2 relaxation time(T2RT) histogram features of extraocular muscles (EOMs) can be used to predict therapy response. Materials and Methods: Forty-five active and moderate-severe TAO patients, who were treated with standard ivMP and underwent orbital MRI before therapy, were retrospectively included in this study. The patients were divided into responsive (n = 24, 48 eyes) and unresponsive group(n = 21, 42 eyes) according to clinical evaluation. Baseline clinical features of patients and histogram-derived T2RT parameters of the EOMs were analyzed and compared. Logistic regression model was conducted to determine independent predictors, and a histogram features nomogram was formulated for personalized prediction. Results: Responsive group displayed lower values for 5th, 10th percentiles (P < 0.050, respectively), and higher values for 75th, 90th, and 95th percentiles, skewness, entropy, and inhomogeneity (P < 0.050, respectively) than unresponsive group. Multivariate logistic regression analysis showed that 95th percentile of >88.1 [odds ratio (OR) = 12.078; 95% confidence interval (CI) = 3.98–36.655, p < 0.001], skewness of >0.31 (OR = 3.935; 95% CI = 2.28–6.788, p < 0.001) and entropy of >3.41 (OR = 4.375; 95% CI = 2.604–7.351, p < 0.001) were independent predictors for favorable response. The nomogram integration of three independent predictors demonstrated optimal predictive efficiency, with a C-index of 0.792. Conclusions: Pre-treatment volumetric T2RT histogram features of EOMs could function to predict the response to ivMP in patients with TAO. The nomogram based on histogram features facilitates the selection of patients who will derive maximal benefit from ivMP. [ABSTRACT FROM AUTHOR]

To evaluate the image quality of magnetic resonance dacryocystography (MRD) using three-dimesional fast spin-echo -Cube (3D-FSE-Cube) and 3D-FSE-Cube-Flex sequences to examine the lacrimal drainage system (LDS). 21 healthy volunteers underwent 3D-FSE-Cube and 3D-FSE-Cube-Flex MRD after topical administration of compound sodium chloride eye drops. Two radiologists assessed LDS images in a blinded fashion. The signal-to-noise ratio of fluid-filling and the contrast-to-noise ratio of fluid-turbinate were compared between the two sequences. Overall image quality, sharpness, artefacts, visualization of anatomical structures, and visibility of LDS segments were also compared. Overall image quality, visualization of anatomic structures, and artefact were significantly better on 3D-FSE-Cube-Flex MRD (p < 0.001, respectively). when compared to 3D-FSE-Cube. 3D-FSE-Cube showed lower fluid-filling signal-to-noise ratio and fluid-inferior turbinate CNR (all p < 0.001). In comparison with 3D-FSE-Cube-Flex, 3D-FSE-Cube produced superior visibility of the upper drainage segments (superior canaliculi, p = 0.003; common canaliculus, p = 0.033; inferior canaliculi, p < 0.001), but inferior in lower-LDS visibility (lacrimal sac, p = 0.001; nasolacrimal duct, p < 0.001). There was no difference in the total number of segments visualized per LDS between the two sequences (p = 0.068). 3D-FSE-Cube-Flex demonstrated superior image quality and visibility of the lower LDS segments. 3D-FSE-Cube showed an advantage in visualizing the upper LDS segments. The combination of these sequences can improve LDS visibility. 3D-FSE-Cube-Flex provides robust water & fat separation and mitigates lower LDS-associated inhomogeneity artefacts. 3D-FSE-Cube shows optimal upper LDS visualization. The combined application of these sequences is a non-invasive and effective method for assessing LDS disease. [ABSTRACT FROM AUTHOR]

We established a chronic dacryocystitis model by injecting of 0.05, 0.1, and 0.15 ml self-curing resin via the lacrimal punctum in rabbits. Animals were randomized into four groups (n=11 animals/group). The control group received 0.15 ml normal saline. Within three months postinjection, epiphora and eye discharge were observed. At the 90th day postlacrimal passage irrigation, CT dacryocystography was performed to find changes in the lacrimal image, and hematoxylin and eosin staining was made to identify pathological changes of the lacrimal sac. Three months postinjection, the rabbits in control group and those who received 0.05 and 0.1 ml self-curing resin failed to develop chronic dacryocystitis. However, 8/11 (72.7%) rabbits those received 0.15 ml self-curing resin were symptomatic and showed complete reflux in lacrimal passage irrigation, indicating the obstruction of the nasolacrimal duct. CT dacryocystography showed that the obstruction was present only in the animals with chronic dacryocystitis. Pathological examinations of chronic dacryocystitis also revealed significantly inflammatory changes, such as mucus epithelium thickening, irregular papillary proliferation, and submucosal fibrous deposition. Local injection of 0.15 ml self-curing resin can induce permanent obstruction of the nasolacrimal duct in rabbits and establish a model of chronic dacryocystitis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the performance of combined T2 mapping and T2 iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) in orbital tissues to predict the therapeutic efficacy of intravenous glucocorticoids (IVGCs) for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO).Method: Sixty-three active and moderate-to-severe TAO patients (responsive group, n = 35; unresponsive group, n = 28) who underwent orbital MRI before receiving IVGCs were retrospectively enrolled. Baseline clinical characteristics and imaging parameters were analyzed and compared between the two groups of different therapeutic efficacy. Binary logistic regression analysis was conducted to determine the independent predictors, the predictive performance of which was evaluated using receiver operating characteristic curve analysis.Results: The mean T2 relaxation time of extraocular muscle (EOM-T2RTmean) (P = 0.001), maximum T2RT of EOM (EOM-T2RTmax) (P = 0.001), mean water fraction of EOM (EOM-WFmean) (P < 0.001), maximum WF of EOM (EOM-WFmax) (P < 0.001) and exophthalmos (P = 0.007) were significantly higher in the responsive group than in the unresponsive group. EOM-T2RTmean (P < 0.001) and EOM-WFmax (P < 0.001) were determined as independent predictors for responsive patients with TAO in the multivariable analysis. Combining EOM-T2RTmean ≥ 77.1 and EOM-WFmax ≥ 91.52 demonstrated optimal efficiency for prediction (area under the curve = 0.844) and optimal predictive sensitivity (77.1%). Setting EOM-WFmax ≥ 91.52 achieved the optimal predictive specificity (89.3%).Conclusions: Pretherapeutic quantitative measurements, based on combining T2 mapping and T2 IDEAL in orbital tissues, are valuable for predicting IVGC treatment response in active and moderate-to-severe TAO. EOM-T2RTmean and EOM-WFmax may become promising IVGC treatment response predictors. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether unilateral primary acquired nasolacrimal duct obstruction (PANDO) changes the volume and water fraction of both lacrimal glands, using three-dimensional fast spin echo (3D-FSE)-Cube-Flex images, and to identify whether the lacrimal gland is a target organ in this disease.Methods: 3D-FSE-Cube-Flex images of both lacrimal glands in 25 healthy volunteers and 31 patients with unilateral PANDO were retrospectively reviewed. The differences in volume and water content in the lacrimal glands between the controls, non-PANDO side, and PANDO side groups were examined. Moreover, the associations between magnetic resonance imaging (MRI) parameters and disease duration were assessed with correlation analysis.Results: The lacrimal gland volumes were not significantly different between the PANDO and non-PANDO side groups, compared to the control group (P = 0.484). However, the gland volumes tended to be increased bilaterally in patients with PANDO. In contrast, the gland water fractions in the PANDO and non-PANDO side groups were significantly higher than those in the control group (P = 0.009 and P = 0.014, respectively), and similar between the non-PANDO and PANDO side groups (P = 0.897). No correlation was found between the disease duration and the gland MRI parameters (volume and water fraction).Conclusions: Both lacrimal glands are affected by unilateral PANDO. A change in the water fraction of these glands appears to precede the change in volume and may be a sensitive early indicator. [ABSTRACT FROM AUTHOR]

The cornea is transparent and innervated by a dense collection of sensory nerves originating from the ocular branch of the trigeminal nerve. This study was designed to comprehensively analyze alterations of corneal sub-basal nerve plexus in a mouse model of tauopathy (P301L transgenic mice) to test the possibility of using corneal nerves as a biomarker for tauopathy. Corneal sensitivity, thickness and epithelial wound healing were measured non-invasively by aeshesiometer, optical coherence tomography and fluorescein staining, respectively. Tau, corneal nerves and immune cells were examined by immunohistochemistry or Western blot. At the early stage of tauopathy, although corneal sensitivity, thickness and nerve fiber density were not greatly altered, corneal nerve abnormalities were observed in the peripheral region of young P301L mice. With aging, the density of abnormal nerves increased, while corneal sensitivity, epithelial thickness, nerve fiber density and length decreased in middle-aged P301L mice compared with WT mice. After corneal epithelial injury in young mice, no difference in reepithelialization was observed between two groups of mice, however, the regeneration of corneal nerves in P301L mice lagged behind WT mice, which was reflected by delayed recovery of corneal sensitivity, decreased corneal nerve density and length and density of CD45+ dendriform cells in P301L mice. In conclusion, our data provide compelling evidence that corneal nerves were changed in a mouse model of tauopathy in an age-dependent manner. Moreover, tau overexpression impairs corneal nerve regeneration. These results suggest that cornea may serve as a promising ocular site for the early diagnosis of tauopathy. • Corneal nerve abnormalities were observed in the peripheral region of young P301L mice at the early stage of tauopathy. • With aging, corneal sensitivity, epithelial thickness, nerve fiber density and length decreased in middle-aged P301L mice. • Corneal nerve regeneration was impaired at the early stage of tauopathy. • Our results suggest that cornea may serve as a promising ocular site for the early diagnosis of tauopathy. [ABSTRACT FROM AUTHOR]

Background & objectives: Tear proteomic changes can be a candidate etiopathogenesis of lacrimal duct obstruction diseases (LDODs). Studies on proteomics have focused primarily on nasolacrimal duct obstruction, and some specific inflammatory cytokines such as interferon (IFN)-α2a, interleukin (IL)-8 and IL-10, have not been investigated. In addition, differences in inflammatory cytokines in tears according to the LDOD subtype have not been reported. This study aimed to quantitatively compare inflammatory cytokines in tears from patients with LDOD and investigate tear-cytokine differences among different LDOD subtypes. Methods: Tear samples were collected from both eyes of 30 patients with unilateral LDOD: five patients with prelacrimal obstruction, five with acute dacryocystitis and 20 with chronic dacryocystitis. The contralateral eyes were used as controls. IFN-α2a, IFN-β, IFN-γ, IL-17A, IL-6, IL-8, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF)-A, induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) were quantified in all samples. Results: The expression of eight cytokines (except for IP-10 and MCP-1) were significantly increased in the affected eyes compared with those in the control eyes. The levels of nine inflammatory cytokines (except for IP-10) in the affected eyes of patients with chronic dacryocystitis were higher than those in the affected eyes of patients with prelacrimal obstruction. In addition, patients with chronic dacryocystitis presented significantly higher IFN-γ level than those with prelacrimal obstruction or acute dacryocystitis. Interpretation & conclusions: Specific pro-inflammatory cytokines were increased in tears of patients with LDOD compared with those in the controls. The specific cytokine profiles observed in the tears of individuals with different LDOD subtypes may be associated with the unique aetiopathogenesis of these conditions. [ABSTRACT FROM AUTHOR]

Corneal neovascularization can cause devastating consequences including vision impairment and even blindness. Corneal inflammation is a crucial factor for the induction of corneal neovascularization. Current anti-inflammatory approaches are of limited value with poor therapeutic effects. Therefore, there is an urgent need to develop new therapies that specifically modulate inflammatory pathways and inhibit neovascularization in the cornea. The interaction of chemokines and their receptors plays a key role in regulating leukocyte migration during inflammatory response. CXCR3 is essential for mediating the recruitment of activated T cells and microglia/macrophages, but the role of CXCR3 in the initiation and promotion of corneal neovascularization remains unclear. Here, we showed that the expression of CXCL10 and CXCR3 was significantly increased in the cornea after alkali burn. Compared with WT mice, CXCR3−/− mice exhibited significantly increased corneal hemangiogenesis and lymphangiogenesis after alkali burn. In addition, exaggerated leukocyte infiltration and leukostasis, and elevated expression of inflammatory cytokines and angiogenic factor were also found in the corneas of CXCR3−/− mice subjected to alkali burn. With bone marrow (BM) transplantation, we further demonstrated that the deletion of CXCR3 in BM-derived leukocytes plays a key role in the acceleration of alkali burn–induced corneal neovascularization. Taken together, our results suggest that upregulation of CXCR3 does not exhibit its conventional action as a proinflammatory cytokine but instead serves as a self-protective mechanism for the modulation of inflammation and maintenance of corneal avascularity after corneal alkali burn. • The expression of CXCL10 and CXCR3 is significantly increased in the cornea after alkali burn. • CXCR3−/− mice exhibit significantly increased corneal hemangiogenesis and lymphangiogenesis after alkali burn. • CXCR3 deletion aggravates leukocyte infiltration, leukostasis and the expression of inflammatory cytokines and angiogenic factor after alkali burn. • The deletion of CXCR3 in bone marrow-derived leukocytes plays a key role in the acceleration of alkali burn–induced corneal neovascularization. [ABSTRACT FROM AUTHOR]

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1) 1 1 IGF1, insulin-like growth factor I. protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R) 2 2 OGD/R, oxygen and glucose deprivation and simulated reperfusion. , and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT 3 3 p-AKT, phospho-AKT. and p-GSK-3β 4 4 AKT, protein kinase B. , thus activating the AKT 5 5 p-GSK-3β, phospho-GSK-3β. signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1 6 6 Mcl-1, myeloid cell leukemia-1. and Bcl-2 7 7 Bcl-2, B-cell lymphoma-2. , and decreased the expression level of the pro-apoptotic protein Bax 8 8 Bax, Bcl-2 associated X protein. , thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP) 9 9 PPP, picropodophyllin. , the inhibitor of insulin-like growth factor I receptors (IGF1R) 10 10 IGF1R, insulin-like growth factor I receptors. . Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment. [ABSTRACT FROM AUTHOR]