Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes.

BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis. RESULTS: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION. CONCLUSION: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON.

Efficacy of part-time patching in preventing recurrence after bilateral lateral rectus recession in children with intermittent exotropia.

BACKGROUND: This study evaluate the efficacy of part-time patching in preventing recurrence after bilateral lateral rectus recession (BLR) in patients with intermittent exotropia (IXT). METHODS: A total of 190 children aged 3-13 years who experienced recurrence after BLR for IXT and received part-time patching were retrospectively reviewed. The patching was prescribed for 2 h per day for more than 6 months. Patients who had a recurrence of 18 PD or more underwent reoperation. Changes in exodeviation and reoperation ratio after part-time patching were analyzed. RESULTS: A total of 34 patients (17.9%) received reoperation after part-time patching, and the reoperation ratio after 2 years was 20.3% as per the Kaplan-Meier survival analysis. Patients with a recurrence of 7 to 10 PD showed a significantly better effect compared to those with a recurrence of more than 10 PD (p < 0.001), and the reoperation ratio was also lower in the survival analysis (p = 0.004). The factor associated with reoperation in patients with part-time patching was the duration between the operation and the initiation of part-time patching (hazard ratio [HR] = 1.006, p = 0.002). CONCLUSIONS: Part-time patching was effective in maintaining the efficacy of surgery and delaying the need of reoperation after BLR. This effect was better in patients with a recurrence of ≤ 10 PD.

Epigenetic programming of chicken germ cells: a comparative review.

Chicken embryos serve as an important model for investigating germ cells due to their ease of accessibility and manipulation within the egg. Understanding the development of germ cells is particularly crucial, as they are the only cell types capable of transmitting genetic information to the next generation. Therefore, gene expression regulation in germ cells is important for genomic function. Epigenetic programming is a crucial biological process for the regulation of gene expression without altering the genome sequence. Although epigenetic programming is evolutionarily conserved, several differences between chickens and mammals have been revealed. In this review, we compared the epigenetic regulation of germ cells in chickens and mammals (mainly mice as a representative species). In mammals, migrating primordial germ cells (precursors for germ cells [PGCs]) undergo global DNA demethylation and persist until sexual differentiation, while in chickens, DNA is demethylated until reaching the gonad but remethylated when sexually differentiated. Prospermatogonia is methylated at the onset of mitotic arrest in mammals, while DNA is demethylated at mitotic arrest in chickens. Furthermore, genomic imprinting and inactivation of sex chromosomes are differentially regulated through DNA methylation in chickens and mammals. Chickens and mammals exhibit different patterns of histone modifications during germ cell development, and non-coding RNA, which is not involved in PGC differentiation in mice, plays an important role in chicken PGC development. Additionally, several chicken-specific non-coding RNAs have been identified. In conclusion, we summarized current knowledge of epigenetic gene regulation of chicken germ cells, comparing that of mammals, and highlighted notable differences between them.

An in vitro validation system for chicken bioreactors using immortalized chicken oviductal epithelial cells.

The utilization of chicken oviductal epithelial cells (OECs) as a bioreactor to produce therapeutic proteins has shown promise, but the time taken to obtain transgenic offspring impedes efficient validation of protein production. To overcome this barrier, we focused on the immortalization of chicken OECs (cOECs) using retroviral vector-mediated c-MYC oncogene expression to establish an in vitro pre-validation system for chicken bioreactors. The resulting immortalized cOECs exhibited sustained proliferation, maintained a normal diploid chicken karyotype, and expressed key oviduct-specific genes (OVA, OVM, LYZ, AVD, and ESR1). Notably, hormonal administration of diethylstilbestrol (DES) or progesterone (P4) upregulated oviduct-specific genes in these cells. To enhance the utility of these immortalized cOECs as an in vitro validation system for chicken bioreactors, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology was employed to knock-in (KI) an enhanced green fluorescence protein (EGFP) gene at the ovalbumin (OVA) locus. The resulting OVA EGFP KI immortalized cOECs secreted both EGFP and OVA proteins into the culture medium, with secretion enhanced under DES treatment. This successful integration of an exogenous gene into cOECs enhances their potential as a versatile in vitro validation system for chicken bioreactors. The established immortalized cOECs overcome previous challenges associated with long-term culture and maintenance, providing a reliable platform for efficient protein production validation. This study presents a comprehensive characterization of the immortalized cOECs, addressing critical limitations associated with in vivo systems and laying a foundation for the development of a streamlined and effective chicken bioreactor model.

Sustainable production of multimeric and functional recombinant human adiponectin using genome-edited chickens.

BACKGROUND: Adiponectin (ADPN) plays a critical role in endocrine and cardiovascular functions, but traditional production methods, such as Escherichia coli and mammalian systems, have faced challenges in generating sufficiently active middle molecular weight (MMW) and high molecular weight (HMW) forms of recombinant human ADPN (hADPN). In our previous study, we proposed genome-edited chickens as an efficient platform for producing multimeric hADPN. However, the consistency of multimeric hADPN expression in this system across generations had not been further investigated. RESULTS: In this study, subsequent generations of ovalbumin (OVA) ADPN knock-in chickens showed stable multimeric hADPN production, yielding ~ 26% HMW ADPN (0.59 mg/mL) per hen. Comparative analysis revealed that egg white (EW)-derived hADPN predominantly consisted of hexameric and HMW forms, similar to serum-derived hADPN. In contrast, hADPN obtained from human embryonic kidney (HEK) 293 and High-Five (Hi-5) cells also exhibited the presence of trimers, indicating variability across different production systems. Furthermore, transcriptional expression analysis of ADPN multimerization-associated endoplasmic reticulum chaperone genes (Ero1-Lα, DsbA-L, ERP44, and PDI) indicated upregulation in the oviduct magnum of ADPN KI hens, suggesting the chicken oviduct magnum as the optimal site for HMW ADPN production. Lastly, the functional analysis demonstrated that EW-derived hADPN significantly reduced lipid droplets and downregulated lipid accumulation-related genes (LOX-1, AT1R, FAS, and FABP4) in human umbilical vein endothelial cells (HUVECs). CONCLUSION: In summary, stable and functional multimeric hADPN can be produced in genome-edited chickens even after generations. This highlights the potential of using chicken bioreactor for producing various high-value proteins.

RNA sequencing analysis of sexual dimorphism in Japanese quail.

Introduction: Japanese quail are of significant economic value, providing protein nutrition to humans through their reproductive activity; however, sexual dimorphism in this species remains relatively unexplored compared with other model species. Method: A total of 114 RNA sequencing datasets (18 and 96 samples for quail and chicken, respectively) were collected from existing studies to gain a comprehensive understanding of sexual dimorphism in quail. Cross-species integrated analyses were performed with transcriptome data from evolutionarily close chickens to identify sex-biased genes in the embryonic, adult brain, and gonadal tissues. Results: Our findings indicate that the expression patterns of genes involved in sex-determination mechanisms during embryonic development, as well as those of most sex-biased genes in the adult brain and gonads, are identical between quails and chickens. Similar to most birds with a ZW sex determination system, quails lacked global dosage compensation for the Z chromosome, resulting in directional outcomes that supported the hypothesis that sex is determined by the individual dosage of Z-chromosomal genes, including long non-coding RNAs located in the male hypermethylated region. Furthermore, genes, such as WNT4 and VIP, reversed their sex-biased patterns at different points in embryonic development and/or in different adult tissues, suggesting a potential hurdle in breeding and transgenic experiments involving avian sex-related traits. Discussion: The findings of this study are expected to enhance our understanding of sexual dimorphism in birds and subsequently facilitate insights into the field of breeding and transgenesis of sex-related traits that economically benefit humans.