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The prompt detection and proper evaluation of necrotic retinal region are especially important for the diagnosis and treatment of acute retinal necrosis (ARN). The potential application of artificial intelligence (AI) algorithms in these areas of clinical research has not been reported previously. The present study aims to create a computational algorithm for the automated detection and evaluation of retinal necrosis from retinal fundus photographs. A total of 149 wide-angle fundus photographs from 40 eyes of 32 ARN patients were collected, and the U-Net method was used to construct the AI algorithm. Thereby, a novel algorithm based on deep machine learning in detection and evaluation of retinal necrosis was constructed for the first time. This algorithm had an area under the receiver operating curve of 0.92, with 86% sensitivity and 88% specificity in the detection of retinal necrosis. For the purpose of retinal necrosis evaluation, necrotic areas calculated by the AI algorithm were significantly positively correlated with viral load in aqueous humor samples (R (2)=0.7444, P

Purpose To compare the levels of inflammatory molecules in tear samples between patients with meibomian gland dysfunction (MGD)-related evaporative dry eye (EDE) and healthy subjects and to analyze the correlations between the levels of tear inflammatory molecules and ocular surface parameters. Methods A total of 30 MGD-related EDE patients (48 eyes) and ten healthy volunteers (15 eyes) were enrolled. Dry eye-related examinations and questionnaires were obtained from all participants. The levels of nine inflammatory molecules were determined through multiplex bead analysis. Results Inflammatory molecules including ICAM-1, IFN-γ, CXCL8/IL-8, IL-6, TNF-α and IL-12p70 were detected in 100% of the patients, while IL-1α, IL-1β and IL-10 were detected in 56.25%, 13.60% and 45.83% of the patients, respectively. Moreover, ICAM-1, IL-8, IL-6, TNF-α, IL-12p70 and IFN-γ were detected in 86.67–100% of the healthy subjects, and the detection rates of IL-10, IL-1α and IL-1β were below 50%. The levels of IL-8, IL-6, IFN-γ and ICAM-1 were significantly higher in the patient group compared with the control group. In addition, IL-8 and IL-6 were negatively correlated with Schirmer I test. Besides, IFN-γ was negatively correlated with tear film breakup time. Furthermore, ICAM-1 and IL-6 were positively correlated with meibography score. Conclusions Collectively, patients with MGD-related EDE had higher levels of inflammatory molecules in their tears, and some molecules were correlated with ocular surface parameters. These findings suggested that inflammation played an important role in MGD-related EDE, and several inflammatory molecules could be used in the diagnosis and the treatment of MGD-related EDE.

Corneal epithelium integrity depends on continuous self-renewing of epithelium and connections between adjacent cells or between the cells and the basement membrane. Self-renewing epithelium cells mainly arise from the continuous proliferation and differentiation of the basal layer and limbal stem cells. The aim of the present study was to generate a bioactive, thermosensitive chitosan–gelatin hydrogel (CHI hydrogel) by incorporating exogenous recombinant human stromal cell–derived factor-1 alpha (SDF-1 alpha) for corneal epithelium regeneration. The exogenous SDF-1 alpha could enhance the stem cells proliferation, chemotaxis and migration, and the expression levels of related genes were significantly elevated in LESCs and mesenchymal stem cells (MSCs) in vitro. Moreover, the MSCs promoted the proliferation and maintained the corneal fate of the LESCs. The rat alkali injury model was used for in vivo study. The injured eyes were covered with CHI hydrogel alone or rhSDF-1 alpha-loaded CHI hydrogel. All rats were followed for 13 days. Histological examination showed that the SDF-1 alpha/CHI hydrogel complex group had a nearly normal thickness; moreover, it was also found that this group could upregulate the expression of some genes and had more ΔNp63-positive cells. The SDF-1 alpha/CHI hydrogel complex group had a more tightly arranged epithelium compared with the control group using transmission electron microscopy (TEM). The mechanism for this may have involved the activation of stem cell homing and the secretion of growth factors via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could provide a new idea for the clinical application. Statement of significance The clarity of cornea is important for normal vision. The loss or dysfunction of LESCs leads to the impairment of corneal epithelium. The complete regeneration of corneal epithelium has not been achieved. Our study demonstrated that the incorporation of rhSDF-1 alpha with CHI hydrogel accelerated corneal epithelium reconstruction with more native structural and functional properties. The mechanism may involve in inducing proliferation and migration of the LESCs and MSCs to the injury site via the SDF-1/CXCR4 chemokine axis. Therefore, SDF-1 alpha/CHI hydrogel complexes could be a practical application for clinical therapy.

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown antifibrotic effects on several diseases. The aims of the present in vitro study were to investigate the antifibrotic effects of bromfenac (a kind of NSAID) on primary human pterygium fibroblasts (HPFs) and primary human conjunctival fibroblasts (HConFs), as well as to explore the possible mechanisms of these effects. Methods The cells used in this study were primary HPFs and HConFs, and profibrotic activation was induced by transforming growth factor-beta1 (TGF-β1). Western blot, quantitative real-time PCR, and immunofluorescence (IF) assays were used to detect the effects of TGF-β1 and bromfenac on the synthesis of fibronectin (FN), type III collagen (COL3), and alpha-smooth muscle actin (α-SMA) in HPFs and HConFs; the changes of signaling pathways were detected by Western blot; cell migration ability was detected by wound healing assay; cell proliferation ability was detected by CCK-8 assay; and pharmaceutical inhibitions of the downstream signaling pathways of TGF-β1 were used to assess their possible associations with the effects of bromfenac. Results Bromfenac suppressed the TGF-β1-induced protein expression of FN (0.59 ± 0.07 folds, P = 0.008), COL3 (0.48 ± 0.08 folds, P = 0.001), and α-SMA (0.61 ± 0.03 folds, P = 0.008) in HPFs. Bromfenac also attenuated TGF-β1-induced cell migration (0.30 ± 0.07 folds, P < 0.001), cell proliferation (0.64 ± 0.03 folds, P = 0.002) and the expression levels of p-AKT (0.66 ± 0.08 folds, P = 0.032), p-ERK1/2 (0.69 ± 0.11 folds, P = 0.003), and p-GSK-3β-S9 (0.65 ± 0.10 folds, P = 0.002) in HPFs. PI3K/AKT inhibitor (wortmannin) and MEK/ERK inhibitor (U0126) reduced the TGF-β1-induced synthesis of FN, COL3, and α-SMA in HPFs. All the results were similar in HConFs. Conclusions Bromfenac protects against TGF-β1-induced synthesis of FN, α-SMA, and COL3 in HPFs and HConFs at least in part by inactivating the AKT and ERK pathways.

Cataracts are the most common eye complications of retinitis pigmentosa (RP). This study aimed to investigate the cytokine profiles of the aqueous humor of RP with cataracts.The aqueous humor was collected from RP eyes with cataract (RP group, n = 20) and age-related cataract eyes (ARC group, n = 20) during cataract surgery. The levels of 37 mediators were measured with multiplex fluorescent bead-based immunoassay and compared across groups. The correlation among chemokines, growth factors, and cytokines was analyzed with Spearman's rank correlation coefficient.Twelve cytokines (IL-1α, IL-1β, IL-4, IL-10, TNF-α, IFN-γ, EGF, GM-CSF, PDGF-AB/BB, TGF-α, BMP-9, and E-selection) were below the limit of detection, and the detection rate of IL-6 was significantly higher in RP group than in the ARC group (P 0.01). Compared with those in the control group, the aqueous humor levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-(IL-)8, interferon gamma-induced protein (IP)-10, hepatocyte growth factor (HGF), platelet-derived growth factor AA (PDGF-AA), matrix metalloproteinase-2 (MMP-2), MMP3, MMP-7, MMP-8, plasminogen activator inhibitor-1 (PAI-1), and thrombospondin-2 (TSP-2) in the RP group increased significantly (P 0.01). A lower level of BMP-4 in the aqueous humor was observed in the RP patients than in the controls (P 0.05).Significantly increased levels of PDGF-AA, MMP2, MMP3, MMP-7, MMP-8, PAI-1, and TSP-2 and lower levels of BMP-4 were found in the aqueous humor of RP patients. This result indicates a disturbance of the extracellular matrix (ECM) and cytokines in RP patients and suggests a possible role of these cytokines in the pathogenesis of capsular contraction syndrome (CCS) in RP patients.

Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. Epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1α signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1α. Blockage of HIF-1α signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1α and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1α signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1α signaling. It provides molecular evidence for potential therapy strategies of treating CNV.