BACKGROUND:Following injury and disruption of the retinal barrier, retinal pigment epithelium can differentiate into a fibroblastic phenotype, leading to proliferation and migration, thereby resulting in pathological conditions such as proliferative vitreoretinopathy and diabetic retinopathy. Previous studies have detected the specific expression of serine/arginine-rich splicing factor 10 (SRSF10) in the retina; however, its specific function has not been thoroughly studied. SRSF10 has been hypothesized to play an important role in retinal function. METHODS:We used Oxford Nanopore Technologies (ONT) full-length transcriptome sequencing and Illumina next-generation transcriptome sequencing platforms to detect splice isoforms affected by SRSF10 and employed improved RNA immunoprecipitation sequencing (iRIP-seq) in human retinal pigment epithelial cells to detect RNA binding with SRSF10. RESULTS:ARPE-19 cells overexpressing SRSF10 showed significant transcriptional differences in the sequencing data obtained from the ONT and Illumina sequencing platforms. Notably, ONT sequencing was more sensitive in detecting new transcripts compared to Illumina. ONT and Illumina sequencing platforms revealed characteristics of alternative splicing events regulated by SRSF10. ONT data showed a primary impact on overlapping exons (olp) events followed by alternative 3' splice site (alt3p) and alt5p, aligning with SRSF10's known functions in exon skipping and inclusion. ONT long-read transcriptome sequencing analysis identified polyadenylation sites (PASs) affected by SRSF10, indicating its role in the dysregulation of polyadenylation in key metabolic genes. In addition, SRSF10 regulates autophagy in cells by influencing the polyadenylation of DEAD-box helicase 58 (DDX58), thereby affecting cell apoptosis. CONCLUSIONS:The study establishes SRSF10 as a significant splicing factor regulating the alternative splicing of multiple genes and interacting with splicing factors. It plays a pivotal role in cell proliferation, apoptosis, and possibly in the epithelial-mesenchymal transition (EMT) of ARPE-19 cells.

OBJECTIVES:This study aims to investigate and predict the therapeutic agents associated with disulfidptosis in periodontitis. DESIGN:The dataset GSE10334 was downloaded from the Gene Expression Omnibus (GEO) database and used to train a least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithm to identify genes associated with disulfidptosis in periodontitis. GSE16134 validation sets, polymerase chain reaction (PCR), and gingival immunofluorescence were used to verify the results.Single-gene Gene Set Enrichment Analysis (GSEA) was performed to explore the potential mechanisms and functions of the characterized genes. Immune infiltration and correlation analyses were performed, and competing endogenous RNA (ceRNA) networks were constructed. Effective therapeutic drugs were then predicted using the DGIdb database, and molecular docking was used to validate binding affinity. RESULTS:Six genes (SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1) associated with disulfidptosis in periodontitis were obtained. Validation results from external datasets and experiments were consistent with the screening results. Single-gene GSEA analysis was mainly enriched for antigen presentation and immune-related pathways and functions.Immune infiltration and correlation analyses revealed significant regulatory relationships between these genes and plasma cells, resting dendritic cell, and activated NK cells. The ceRNA network was visualized. And ME-344, NV-128, and RILUZOLE, which have good affinity to target genes, were identified as promising agents for the treatment of periodontitis. CONCLUSIONS:SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis.

The process of wound healing in the dental pulp is characterized by intricate interplay of signalling cascades, cellular responses, and extracellular matrix (ECM). The objective of this research was to examine the intricate interaction between signalling cascades, cellular responses, and extracellular matrix (ECM) dynamics that comprise the wound healing process of dental pulp. We conducted a controlled laboratory analysis of transcriptomic landscape of dental pulp tissues, including both healthy and inflamed samples, utilizing single-cell RNA sequencing. We identified significant change in cellular composition under carious conditions by analysing samples from 50 patients. Specifically, the proportion of immune cells increased from 25% to 40%, while the proportion of fibroblasts decreased from 20% to 10%. A transition towards ECM remodelling and fibrosis was indicated by this change. In addition, substantial increase inexpression of critical genes including COL1A1, FN1, IL-1B, IL-6 and TNC was detected, indicating that the extracellular matrix (ECM) was actively remodelled and that a robust inflammatory response was present, both of which are vital for tissue repair. Increased cell-cell interactions among B cells, plasma cells, macrophages and MSCs, and fibroblasts were highlighted in our study, demonstrating the intricate cellular dynamics that occur in response to dental pulp injury. The knowledge gained regarding the cellular and molecular processes underlying pulp wound healing contributed to the advancement of knowledge regarding pulp pathology and regeneration. Moreover, it established a foundation for creation of targeted therapeutic interventions that seek to maximize pulp repair and regeneration. This study represented noteworthy achievement in the field of dental surgery, establishing a solid groundwork for subsequent investigations into regenerative medicine, wound healing, and dental tissue restoration.

OBJECTIVES:Demineralized bone matrix (DBM) is a well-established bone graft material widely accepted by dentists and the public for its favorable osteoconductivity and osteoinductive potential. This article aimed to provide a narrative review of the current therapeutic applications and limitations of DBM in maxillofacial bone defects.STUDY SELECTION, DATA, AND SOURCES:Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic reviews. MEDLINE, PubMed, and Google Scholar were searched using keywords.CONCLUSIONS:Some evidence supported the therapeutic application of DBM in periodontal intrabony defects, maxillary sinus lifts, ridge preservation, ridge augmentation, alveolar cleft repair, orthognathic surgery, and other regional maxillofacial bone defects. However, the limitations of DBM should be considered when using it, including potential low immunogenicity, instability of osteoinductive potential, handling of the graft material, and patient acceptance.CLINICAL SIGNIFICANCE:With the increasing demand for the treatment of maxillofacial bone defects, DBM is likely to play a greater role as a promising bone graft material. Safe and effective combination treatment strategies and how to maintain a stable osteoinductive potential will be the future challenges of DBM research.

This study compares the optical quality of zonal refractive multifocal and diffractive bifocal intraocular lenses (IOLs) and visual outcomes after implantation in 93 patients(93 eyes) with cataracts and high myopia. A retrospective analysis was conducted to measure visual acuity at far, intermediate, and near distances, defocus curves, wavefront aberrations, modulation transfer function (MTF), a Quality of Vision questionnaire (QoV) and visual quality self-evaluation were examined at 3 months. The results demonstrated the ZMB group showed better uncorrected near visual acuity (P < 0.01), and the MF15 group showed better uncorrected intermediate visual acuity (P < 0.001). The ZMB group provided better MTF than the MF15 group (P < 0.01) but demonstrated a worse QoV score, especially for the severity of glare, halo, and starburst (P < 0.05). The satisfaction score and spectacle independence rate in the ZMB group were higher than in the MF15 group (P < 0.01). LS-313MF15 and TecnisZMB00 offered excellent visual restoration, stable distance visual acuity, and good subjective visual function.

Introduction The objective of this study is to report a case of complete recovery of the retinal pigment epithelium (RPE) layer after spontaneous large serous RPE tear and explore the possible RPE repair mechanism. Case description A 63-year-old male patient developed serous detachment of the RPE in the macula of his left eye. During the follow-up period, an oval-shaped RPE tear spontaneously occurred in the macular area, and fundus autofluorescence showed that the torn area was 6.59 mm 2 . Spectral-domain optical coherence tomography (OCT) revealed that the subretinal fluid had been absorbed and that the continuity of the RPE layer was gradually restored from the periphery to the center over the course of 9 months. Moreover, visual acuity (VA) in the left eye was restored to 20/20, and there was no significant difference in macular function between the two eyes, as measured by multifocal electroretinography, at the last follow-up. In addition, the patient received no special treatment during the entire follow-up period. Conclusion The integrity of the RPE layer can be restored completely after extensive RPE tear, and recovered RPE may allow the recovery of macular function.

Background Herein, we report two cases of unilateral retinal pigment epithelium dysgenesis (URPED) in Chinese patients and explore the relationship between URPED and combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). Case presentation The lesion margins in the two cases showed pathognomonic clinical features of URPED, namely, a scalloped reticular margin in hyperplastic retinal pigment epithelium and mild fibrosis. The hypoautofluorescence observed by fundus autofluorescence was inverted compared with that observed by fundus fluorescence angiography. A large amount of fibroglial proliferation and disorganization of the retina involving the whole layer, which are also found in peripapillary CHRRPE, were found in the lesions. Conclusions URPED appears to share some clinical features with CHRRPE, and the relationship between URPED and CHRRPE needs further study.

Background RNA binding proteins (RBPs)-mediated regulation plays important roles in many eye diseases, including the canonical RBP CELF1 in cataract. While the definite molecular regulatory mechanisms of CELF1 on cataract still remain elusive. Methods In this study, we overexpressed CELF1 in human cultured lens epithelial SRA01/04 cells and applied whole transcriptome sequencing (RNA-seq) method to analyze the global differences mediated by CELF1. We then analyzed public RNA-seq and CELF1-RNA interactome data to decipher the underlying mechanisms. Results The results showed that transcriptome profile was globally changed by CELF1 overexpression (CELF1-OE). Functional analysis revealed CELF1 specifically increased the expression of genes in extracellular matrix disassembly, extracellular matrix organization, and proteolysis, which could be classified into matrix metalloproteinases (MMPs) family. This finding was also validated by RT-qPCR and public mouse early embryonic lens data. Integrating analysis with public CELF1-RNA interactome data revealed that no obvious CELF1-binding peak was found on the transcripts of these genes, indicating an indirectly regulatory role of CELF1 in lens epithelial cells. Conclusions Our study demonstrated that CELF1-OE promotes transcriptional level of MMP genes; and this regulation may be completed by other ways except for binding to RNA targets. These results suggest that CELF1-OE is implicated in the development of lens, which is associated with cataract and expands our understanding of CELF1 regulatory roles as an RNA binding protein.

Background This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis. Methods Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients. Results Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy. Conclusions RPE and choroidal atrophy were found to play an important role in the development of macular caldera.

Cataract is a global eye disease caused by the opacification of lens, while its underlying molecular pathogenesis is not clear, making it difficult for prevention. CELF1, an RNA binding protein, mediates Alternative Splicing (AS) of genes involved in diverse diseases and regulates development or defects of lens. Utilizing transcriptome-wide approaches, we analyzed and compared AS patterns between human lens epithelial cells (SRA01/04) with CELF1 overexpression (CELF1-OE) and control cells. Extensive changes in AS patterns upon CELF1-OE were identified in SRA01/04 cells. We finally identified 840 CELF1-regulated AS events (RASEs) and found that CELF1-OE preferred to repress exon skipping events in SRA01/04 cells. CELF1-regulated AS genes were enriched in the regulation of DNA repair, cellular response to DNA damage stimulus, and apoptosis pathways (including HMGA2, CSNK1E, and YAP1). These biological functions and pathways have been reported to be associated with lens development or other eye diseases. To further explore the mechanisms of CELF1 in regulating AS genes, we downloaded and re-analyzed a set of CELF1-RNA interactome data. We found that 194 genes were bound and regulated by CELF1 at the AS level. 10 genes involved in DNA repair-related pathways were also bound by CELF1. Motif analysis for CELF1-bound peaks and splicing sites of RASEs showed that CELF1 regulates AS by binding to the AGGU[AG]AG motif in SRA01/04 cells. CELF1 could mediate AS of DNA repair-related genes through directly binding to their transcripts with distinct motif bias. The functional mechanism of CELF1 may ultimately participate in cataract formation and lens development.

Background Numerous cases with ocular toxicity secondary to tamoxifen have been reported, and became more apparent with keratopathy, cataract, optic neuritis, macular holes, crystalline retinopathy with or without cystoid macular edema (CME). Withdrawing tamoxifen with the approval of the oncologist is the major treatment for cases with tamoxifen-induced retinopathy. Case presentation We herein reported a patient with a two-year history of painless and reduced visual acuity in both eyes who received tamoxifen therapy for 6 years. Tamoxifen-induced rentinopathy with CME showed significant development even though the patient has already discontinued tamoxifen treatment for 6 months. Anatomic improvements after intravitreal ranibizumab injection in both eyes were significant but were temporary. Surprisingly, CME in both eyes has been resolved spontaneously after 10 months in the penultimate visit without any therapy. Conclusion Intravitreal ranibizumab injection temporarily improved the anatomy of the eyes in a case with tamoxifen-induced CME, and only tamoxifen withdrawal can bring a sustained effect.

AIM To explore the mRNA and pathways related to retinoblastoma (RB) genesis and development. METHODS Microarray datasets GSE29683 (human) and GSE29685 (mouse) were downloaded from NCBI GEO database. Homologous genes between the two species were identified using WGCNA, followed by protein-protein interaction (PPI) network construction and gene enrichment analysis. Disease-related miRNAs and pathways were retrieved from miR2Disease database and Comparative Toxicogenomics Database (CTD), respectively. RESULTS A total of 352 homologous genes were identified. Two pathways including "cell cycle" and "pathway in cancer" in CTD and enrichment analysis were identified and seven miRNAs (including hsa-miR-373, hsa-miR-34a, hsa-miR-129, hsa-miR-494, hsa-miR-503, hsa-let-7 and hsa-miR-518c) were associated with RB. miRNAs modulate "cell cycle" and "pathway in cancer" pathways via regulating 13 genes (including CCND1, CDC25C, E2F2, CDKN2D and TGFB2). CONCLUSION These results suggest that these miRNAs play crucial roles in RB genesis through "cell cycle" and "pathway in cancer" pathways by regulating their targets including CCND1, CDC25C, E2F2 and CDKN2D.

Background: As a disorder occurs in the eyes, keratoconus (KC) is induced by the thinning of the corneal stroma. This study was designed to reveal the key long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs involved in the mechanisms of KC. Methods: Transcriptome RNA-seq data set GSE112155 was acquired from the Gene Expression Omnibus database, which contained 10 KC samples and 10 myopic control samples. Using the edgeR package, the differentially expressed (DE)-mRNAs between KC and control samples were screened. The DE-lncRNAs and DE-miRNAs in this data set were identified using the HUGO Gene Nomenclature Committee (HGNC). Using the pheatmap package, bidirectional hierarchical clustering of the DE-RNAs was conducted. Then, an enrichment analysis of the DE-mRNAs was performed using the DAVID tool. Moreover, a competitive endogenous RNA (ceRNA) regulatory network was built using the Cytoscape software. After KC-associated pathways were searched within the Comparative Toxicogenomics Database, a KC-associated ceRNA regulatory network was constructed. Results: There were 282 DE-lncRNAs (192 upregulated and 90 downregulated), 40 DE-miRNAs (29 upregulated and 11 downregulated), and 910 DE-mRNAs (554 upregulated and 356 downregulated) between the KC and control samples. A total of 34 functional terms and 9 pathways were enriched for the DE-mRNAs. In addition, 6 mRNAs (including PPARG, HLA-B, COL4A1, and COL4A2), 5 miRNAs (including miR-181a), 9 lncRNAs (including XIST), and the XIST-miR-181a-COL4A1 axis were involved in the KC-associated ceRNA regulatory network. Conclusions: PPARG, HLA-B, COL4A1, COL4A2, miR-181a, and XIST might be correlated with the development of KC. Further, the XIST-miR-181a-COL4A1 axis might be implicated in the pathogenesis of KC.

Purpose: This study was aimed at identifying differentially expressed genes (DEGs) in bacterial and fungal keratitis. The candidate genes can be selected and quantified to distinguish between causative agents of infectious keratitis to improve therapeutic outcomes. Methods: The expression profile of bacterial or fungal infection, and normal corneal tissues were downloaded from the Gene Expression Omnibus. The limma package in R was used to screen DEGs in bacterial and fungal keratitis. The Co-Express tool was used to calculate correlation coefficients of co-expressed genes. The "Advanced network merge" function of Cytoscape tool was applied to obtain a fusional co-expression network based on bacterial and fungal keratitis DEGs. Finally, functional enrichment analysis by DAVID software and KEGG analysis by KOBAS of DEGs in fusion network were performed. Results: In total, 451 DEGs in bacterial keratitis and 353 DEGs in fungal keratitis were screened, among which 148 DEGs were found only in bacterial keratitis and 50 DEGs only in fungal keratitis. Besides, 117 co-expressed gene pairs were identified among bacterial keratitis DEGs and 87 pairs among fungal keratitis DEGs. In total, nine biological pathways and seven KEGG pathways were screened by analyzing DEGs in the fusional co-expression network. Conclusion: TLR4 is the representative DEG specific to bacterial keratitis, and SOD2 is the representative DEG specific to fungal keratitis, both of which are promising candidate genes to distinguish between bacterial and fungal keratitis.