Metabolomic Profiling of the Aqueous Humor in Patients with Pediatric Cataract.

Pediatric cataract, including congenital and developmental cataract, is a kind of pediatric vision-threatening disease with extensive phenotypic heterogeneity and multiple mechanisms. We aimed to investigate the metabolite profile of aqueous humor (AH) in patients with pediatric cataracts, and identify underlying mutual correlations between differential metabolites. Metabolomic profiles of AH were analyzed and compared between pediatric cataract patients (n=33) and age-related cataract patients without metabolic diseases (n=29), using global untargeted metabolomics with ultra-high-performance liquid chromatography tandem mass spectrometry. Principal component analysis, partial least squares discriminant analysis and heat map were applied. Enriched pathway analysis was conducted using Kyoto Encyclopedia of Genes and Genomes. Receiver-operating characteristic (ROC) analyses were employed to select potential biomarkers. A total of 318 metabolites were identified, of which 54 differential metabolites (25 upregulated and 29 downregulated) were detected in pediatric cataract group compared with controls (variable importance of projection > 1.0, fold change ≥ 1.5 or ≤ 0.667 and P < 0.05). A significant accumulation of N-Acetyl-Dl-glutamic acid was observed in pediatric cataract group. The differential metabolites were mainly enriched in histidine metabolism (increased L-Histidine and decreased 1-Methylhistamine) and the tryptophan metabolism (increased N-Formylkynurenine and L-Kynurenine). 5-Aminosalicylic acid showed strong positive mutual inter-correlation with L-Tyrosinemethylester and N,N-Diethylethanolamine, both of which were down-regulated in pediatric cataract group. The ROC analysis implied 11 metabolites served as potential biomarkers for pediatric cataract patients (all area under the ROC curve ≥ 0.900). These results illustrated novel potential metabolites and metabolic pathways in pediatric cataract, which provides new insights into the pathophysiology of pediatric cataract.

Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming.

Retinal degeneration diseases affect millions of people worldwide but are among the most difficult eye diseases to cure. Studying the mechanisms and developing new therapies for these blinding diseases requires researchers to have access to many retinal cells. In recent years there has been substantial advances in the field of biotechnology in generating retinal cells and even tissues in vitro, either through programmed sequential stem cell differentiation or direct somatic cell lineage reprogramming. The resemblance of these in vitro-generated retinal cells to native cells has been increasingly utilized by researchers. With the help of these in vitro retinal models, we now have a better understanding of human retinas and retinal diseases. Furthermore, these in vitro-generated retinal cells can be used as donor cells which solves a major hurdle in the development of cell replacement therapy for retinal degeneration diseases, while providing a promising option for patients suffering from these diseases. In this review, we summarize the development of pluripotent stem cell-to-retinal cell differentiation methods, the recent advances in generating retinal cells through direct somatic cell reprogramming, and the translational applications of retinal cells generated in vitro. Finally, we discuss the limitations of the current protocols and possible future directions for improvement.

Hotspots and frontiers of genetic research on pediatric cataracts from 2013 to 2022: a scientometric analysis.

AIM: To explore the hotspots and frontiers of genetic research on pediatric cataracts. METHODS: Global publications from 2013 to 2022 related to genes in pediatric cataracts were extracted from the Web of Science Core Collection, and were analyzed in terms of the publication counts, countries, journals, authors, keywords, cited references, subject categories, and the underlying hotspots and frontiers. RESULTS: Totally 699 publications were included in the final analysis. The predominant actors were identified, with China (n=240) and PLoS One (n=33) being the most productive country and journal respectively. The research hotspots extracted from keywords were crystallin gene mutations, pathogenicity evaluation, phenotypes of ocular and neurodevelopmental abnormalities, genes encoding membrane proteins, and diagnosis of multisystemic disorders. The co-cited articles formed 10 clusters of research topics, including FYCO1 (56 items), mutation screening (43 items), gap junction (29 items), the Warburg Micro syndrome (29 items), ephrin-A5 (28 items), novel mutation (24 items), eye development and function (22 items), cholestanol (7 items), OCRL (6 items), and pathogenicity prediction (3 items). The research frontiers were FYCO1, ephrin-A5, and cholestanol. Cell biology showed the strongest bridging effects among different disciplines in the field (betweenness centrality=0.44). CONCLUSION: With the progress in next-generation sequencing and multidisciplinary collaboration, genetic research on pediatric cataracts broadens the knowledge scope of the crystalline lens, as well as other organs and systems, shedding light on the molecular mechanisms of systemic diseases. Cell biology may integrate multidisciplinary content to address cutting-edge issues in the field.

The lens epithelium as a major determinant in the development, maintenance, and regeneration of the crystalline lens.

The crystalline lens is a transparent and refractive biconvex structure formed by lens epithelial cells (LECs) and lens fibers. Lens opacity, also known as cataracts, is the leading cause of blindness in the world. LECs are the principal cells of lens throughout human life, exhibiting different physiological properties and functions. During the embryonic stage, LECs proliferate and differentiate into lens fibers, which form the crystalline lens. Genetics and environment are vital factors that influence normal lens development. During maturation, LECs help maintain lens homeostasis through material transport, synthesis and metabolism as well as mitosis and proliferation. If disturbed, this will result in loss of lens transparency. After cataract surgery, the repair potential of LECs is activated and the structure and transparency of the regenerative tissue depends on postoperative microenvironment. This review summarizes recent research advances on the role of LECs in lens development, homeostasis, and regeneration, with a particular focus on the role of cholesterol synthesis (eg., lanosterol synthase) in lens development and homeostasis maintenance, and how the regenerative potential of LECs can be harnessed to develop surgical strategies and improve the outcomes of cataract surgery (Fig. 1). These new insights suggest that LECs are a major determinant of the physiological and pathological state of the lens. Further studies on their molecular biology will offer possibility to explore new approaches for cataract prevention and treatment.

Publication delays and associated factors in ophthalmology journals.

Introduction: This study aimed to evaluate the publication delays and correlative factors of peer-reviewed ophthalmology journals. Methods: The ophthalmology journals listed in the Journal Citation Report 2020 were retrieved from the Web of Science database. The first original research article of each journal issue from January to December 2020 was extracted, and its submission, final revision, acceptance, and publication dates were obtained. Information on impact factors, advance online publication (AOP) status, open access (OA) rate and acceptance rate in 2020 was also collected. The correlations between publication delays and potential associated factors were analyzed. Results: A total of 58 ophthalmology journals were included and information on 685 articles was collected. The median times from submission to acceptance, from acceptance to publication, and from submission to publication were 118.0 (IQR, 74.0-185.0) days, 31.0 (IQR, 15.0-64.0) days, and 161.0 (IQR, 111.0-232.0) days, respectively. A higher impact factor was correlated with shorter delays of acceptance and publication (P < 0.05). There was a positive correlation between acceptance rates and publication delays (r = 0.726, P = 0.007). Forty-seven (81.03%) journals provided AOP. There was no statistically significant difference for impact factors and publication delays between journal with and without AOP (all P > 0.05). No correlation between OA rate and publication delays or impact factors was detected (all P > 0.05). Conclusions: Journals with higher impact factors and lower acceptance rates tend to have quicker publication processes. No significant associations were detected between publication delays and AOP or OA rate.