Shiqi Ling

Corneal transplantation is a critical approach for some vision loss patients. However, the rejection of human organs severely affects the survival rate of

Purpose: Previous studies have shown that Bifidobacterium animalis subsp. lactis BB-12 plays a role in maintaining the intestinal barrier and regulating inflammation; however, its potential connection to ocular diseases has not been thoroughly explored. Diabetic retinopathy (DR) is a common ocular complication of diabetes and is closely associated with metabolic dysregulation. This study investigated whether BB-12 supplementation could affect systemic diabetic symptoms, the progression of DR, and the stability of gut microbiota. Materials and methods: Diabetic db/db mice were utilized to monitor metabolic parameters, assess hepatic and lipid profiles, evaluate retinal function via ERG, and examine retinal morphology through OCT and HE staining. Treg/Th17 balance was analyzed by flow cytometry, and gut microbiota composition was profiled using 16S rRNA sequencing. Results: The results showed that BB-12 reduced obesity, decreased hepatic steatosis, improved retinal blood vessel health and vision, and influenced both the Treg/Th17 balance and gut dysbiosis in diabetic mice. Conclusions: These findings lay the groundwork for regulatory role of intestinal microbiota on systemic and ocular complications of diabetes, and further examination of the gut-retina axis.

The success rates of high-risk corneal transplantation are significantly hindered by immunological rejection. Umbilical cord mesenchymal stem cells (UC-MSCs) have emerged as a potential solution to improve graft outcomes. Toll-like receptors (TLRs) play pivotal roles in the immune response, however, their specific functions in UC-MSC-based treatments for corneal graft rejection requires further investigation. New Zealand rabbits that underwent high-risk corneal transplantation were treated with UC-MSC-coated contact lenses (MSCohi-O), while blank lenses and untreated grafts served as controls. Clinical manifestations related to rejection were assessed. RNA-seq was performed on the grafts. GSEA, CIBERSORT, and flow cytometry analyses were performed to investigate the activation of signaling pathways and immune changes. The microarray dataset GSE68610, which contains transcriptome data for normal human UC-MSCs and UC-MSCs treated with cytokines, was analyzed to evaluate TLR expression and identify the key factors involved in the anti-inflammatory effect of UC-MSCs. Overexpression and knockout of TLR3 were performed in UC-MSCs, and the therapeutic effects of TLR3-activated and -inactivated UC-MSCs were compared in a high-risk corneal transplantation model. MSCohi-O treatment alleviated corneal opacity and edema, inhibited neovascularization, promoted epithelialization, and prolonged the survival time of corneal grafts (all p < 0.05). GSEA revealed that the allograft rejection pathway was upregulated in untreated grafts and downregulated in UC-MSC-treated grafts. Increased numbers of Tregs and decreased numbers of Th17 cells were observed in UC-MSC-treated corneas. An analysis of the GSE68610 dataset revealed that TLR3 expression was upregulated in cytokine-activated UC-MSCs, suggesting that TLR3 is a potential regulator of the immunosuppression function of UC-MSCs. TLR3-overexpressing UC-MSCs exhibited enhanced suppression of rejection in high-risk corneal transplants, whereas TLR3 knockdown diminished these effects. This study shows that the localized application of UC-MSC-coated contact lenses is capable of inhibiting rejection in high-risk corneal transplantation. TLR3-overexpressing UC-MSCs have enhanced antirejection and immunomodulatory effects. This research could offer a safer and more effective therapeutic strategy to prevent corneal transplant rejection.

Purpose: While deep learning (DL) has demonstrated significant utility in ocular diseases, no clinically validated algorithm currently exists for diagnosing neuromyelitis optica (NMO). This study aimed to develop a proof-of-concept multimodal artificial intelligence (AI) diagnostic model that synergistically integrates ultrawide field fundus photographs (UWFs) with clinical examination data for predicting the onset and stage of suspected NMO.Methods: The study utilized the UWFs of 330 eyes from 285 NMO patients and 1,288 eyes from 770 non-NMO participants, along with clinical examination reports, to develop an AI model for predicting the onset or stage of suspected NMO. The performance of the AI model was evaluated based on the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.Results: The multimodal AI diagnostic model achieved an AUC of 0.9923, a maximum Youden index of 0.9389, a sensitivity of 97.0% and a specificity of 96.9% in predicting the prevalence of NMO on test data set.Conclusion: Our study demonstrates the feasibility of DL algorithms in diagnosing and predicting of NMO.

Purpose To characterize current global status and frontiers in the field of vitreous floaters research. Methods The Web of Science Core Collection was used to retrieve the international scientific publications on vitreous floaters from 1999 to 2023. Scientometric data were analyzed and visualized using VOSviewer (1.6.18 Edition) and CiteSpace (6.3.R1). Results A total of 547 articles with 8940 citations were identified. The annual number of publications and citations dramatically increased during the period. The USA was the most productive country with 26.33% of the total articles and 40.44% of the total citations. The USA collaborated more frequently with countries including China and Japan. The most productive affiliation was University of California System and the most productive author was Sebag Julia from the USA. Retina and BMC Ophthalmology published the highest percentage of articles (4.94%) while American Journal of Ophthalmology received the most citations (6.66%). The most frequent subject category was “Ophthalmology” (n = 356, 52%). “Vitrectomy”, “vitreous floaters”, “uveitis”, “vitreous opacity”, and “YAG vitreolysis” were the top 5 frequent keywords. The efficacy and safety of management for vitreous floaters turned out to be a recent research hot spot, especially the pharmacologic vitreolysis agents and Nd:YAG laser vitreolysis. Conclusions The optimized treatment of vitreous floaters emerged as a research hot spot. This study provides a broad insight of the status and frontiers in vitreous floaters, which might guide future research direction in this field.

Corneal alkali burns can cause persistent inflammation and corneal neovascularization. In this study, we divided corneal alkali burned rabbits into the untreated group, the blank lens group, the radiation-treated umbilical cord mesenchymal stem cells (UCMSC) lens group, and the UCMSC I.V. group, and then measured corneal inflammation, neovascularization and corneal injury repair via slit lamp microscopy, captured anterior segment optical coherence tomography (AS-OCT), and performed hematoxylin-eosin staining. Compared with those in the other experimental groups, radiation-treated UCMSC lenses significantly decreased inflammatory index (IF) scores, areas of corneal blood vessels and corneal epithelial injury. The expression of interleukin (IL)-17 in corneas treated with radiation-treated UCMSC lenses was lower than that in corneas treated with blank lenses, and radiation-treated UCMSC lenses exhibited greater expression of IL-4 and signal transducer and activator of transcription 1 (STAT1), while the expression of cluster of differentiation-3G (CD3G), a linker for the activation of T cells (LAT), IL-6, IL-1B, CC chemokine receptor 6 (CCR6) and IL-23 exhibited the opposite effects (all P < 0.05). Our findings demonstrated that irradiated UCMSC-coated high oxygen-permeable hydrogel lenses on the ocular surface inhibited corneal angiogenesis and inflammation after corneal alkaline burns. The downregulation of Th17 cell differentiation might be responsible for these effects.

Background: Although autoimmune complications of COVID-19 have aroused concerns, there is no consensus on its ocular complications. Sjögren’s syndrome is an autoimmune disease accompanied by the ocular abnormality keratoconjunctivitis sicca (SS-KCS), which may be influenced by COVID-19. Thereby, we explored the possible interaction between COVID-19 and SS-KCS, and we aimed to elucidate the potential correlated mechanism. Methods: Differentially expressed genes (DEGs) in COVID-19 and SS-KCS transcriptome data obtained from the gene expression omnibus database were identified, and COVID-19-related genes were screened using weighted gene coexpression network analysis. Common genes were verified using four machine-learning diagnostic predictors. The clinical relationship between the two common hub genes of COVID-19 was analyzed. Finally, the immune cell types infiltrating the microenvironment in the COVID-19 dataset were analyzed using CIBERSORT, and the interrelation between key genes and differentially infiltrating immune cells was verified via Pearson correlation. Results: Ten potential primary hub mRNAs were screened by intersecting the COVID-19 DEGs, SS-KCS DEGs, and WGCNA genes. After a multifaceted evaluation using four mainstream machine-learning diagnostic predictors, the most accurate and sensitive random forest model identified CR1 and TAP2 as the common hub genes of COVID-19 and SS-KCS. Together with the clinical information on COVID-19, the expression of CR1 and TAP2 was significantly correlated with the status and severity of COVID-19. CR1 and TAP2 were significantly positively correlated with M0 and M2 macrophages, neutrophils, and CD4+ memory resting T cells and negatively correlated with activated NK cells, monocytes, and CD8+ T cells. Conclusions: We validated the hub genes associated with both COVID-19 and SS-KCS, and we investigated the immune mechanisms underlying their interaction, which may help in the early prediction, identification, diagnosis, and management of SARS-CoV-2 infection-related SS-KCS syndrome or many other immune-related complications in the long COVID period.