ABSTRACT Cataract is a leading cause of visual impairment worldwide, and its prevalence is increasing with population aging. The majority are age‐related cataracts (ARC), clinically classified into nuclear, cortical, and posterior subcapsular cataracts (PSC) by opacity location. Mechanisms of cataractogenesis remain incompletely understood. While cortical and nuclear cataracts are largely attributed to crystallin aggregation, such protein‐centric mechanisms fail to explain the early onset and axial location of PSC. Morphologically, PSC resembles posterior capsule opacification (PCO), a secondary cataract driven by epithelial–mesenchymal transition (EMT) of lens epithelial cells (LECs), suggesting LEC‐EMT may also contribute to PSC. Using clinically stratified human lens samples, we confirmed EMT marker expression across PSC subtypes. Transcriptomic profiling revealed that LECs, the lens's sole metabolically active cells, in age‐related PSC (ARC‐PSC), compared with age‐related nuclear cataract (ANC) and clear lenses, exhibit elevated EMT signatures tightly linked to senescence‐associated inflammatory signaling. Aqueous humor (AqH) profiling demonstrated a pro‐inflammatory milieu across PSC subtypes, with IL‐17A uniquely elevated in ARC‐PSC, consistent with transcriptomic findings. Integrated analyses support a model in which senescence functions as an upstream driver, whereby senescent LECs release SASP factors, including IL‐17A, that activate NF‐κB signaling to amplify inflammation, reinforce senescence, and drive EMT. In vitro, senolysis and IL‐17A blockade disrupted this loop, attenuating senescence‐ and EMT‐associated phenotypes. Collectively, our study demonstrates that senescent LECs sustain an IL‐17A–NF‐κB circuit that drives EMT and accelerates ARC‐PSC progression, positioning ARC‐PSC as a unique human context to study senescence‐induced epithelial remodeling in aging tissues.
Twice‐daily administration improves the effectiveness of 0.01% atropine for controlling myopia in slowing axial elongation and refractive progression
Abstract Purpose It remains unclear whether increasing the frequency of administration of 0.01% atropine improves its effectiveness in slowing axial elongation or refractive progression. This study compared twice‐daily 0.01% atropine administration and traditional once‐nightly administration. Methods A hybrid design was adopted incorporating both retrospective and prospective elements, with participants observed for 1 year. The control group (received saline eye drops) and once‐daily 0.01% atropine group (Atropine‐1 group) were derived from two previous trials, while the twice‐daily 0.01% atropine group (Atropine‐2 group) was enrolled prospectively. A total of 163 participants were included in the intention‐to‐treat set, with 51, 70 and 42 participants in the control, Atropine‐1 and Atropine‐2 groups, respectively. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in cycloplegic spherical equivalent refraction (SER). Results Compared with the control group (0.48 ± 0.22 mm), both Atropine‐1 (0.26 ± 0.17 mm) and Atropine‐2 (0.15 ± 0.18 mm) groups showed significantly reduced AL elongation ( p < 0.001). Notably, Atropine‐2 significantly improved slowing of AL elongation compared with Atropine‐1 ( p = 0.008). The result of the secondary outcome (adjusted SER change) was consistent. Atropine‐2 was significantly more effective in slowing SER progression (−0.15 ± 0.37 D) than Atropine‐1 (−0.41 ± 0.50 D) ( p = 0.02). Based on a multivariable model, age was identified as the key covariate to perform subgroup analyses. In the younger subgroup (8–10 years), AL elongation was significantly reduced in the Atropine‐2 group (0.16 ± 0.17 mm) compared with the Atropine‐1 group (0.36 ± 0.22 mm; p = 0.002). In the older subgroup (10–12 years), there was no significant difference in progression. Consistent results were observed in the sensitivity analyses based on the per‐protocol set. Conclusion Twice‐daily administration of 0.01% atropine was more effective than once daily in slowing AL elongation and SER progression in children 8 to 10 years of age. Further investigation with extended follow‐up is warranted to substantiate this finding.
CD8 positive T-cells decrease neurogenesis and induce anxiety-like behaviour following hepatitis B vaccination
Abstract Mounting evidence indicates the involvement of peripheral immunity in the regulation of brain function, influencing aspects such as neuronal development, emotion, and cognitive abilities. Previous studies from our laboratory have revealed that neonatal hepatitis B vaccination can downregulate hippocampal neurogenesis, synaptic plasticity and spatial learning memory. In the current post-epidemic era characterized by universal vaccination, understanding the impact of acquired immunity on neuronal function and neuropsychiatric disorders, along with exploring potential underlying mechanisms, becomes imperative. We employed hepatitis B vaccine-induced CD3 positive T cells in immunodeficient mice to investigate the key mechanisms through which T cell subsets modulate hippocampal neurogenesis and anxiety-like behaviours. Our data revealed that mice receiving hepatitis B vaccine-induced T cells exhibited heightened anxiety and decreased hippocampal cell proliferation compared to those receiving phosphate-buffered saline-T cells or wild-type mice. Importantly, these changes were predominantly mediated by infiltrated CD8+ T cells into the brain, rather than CD4+ T cells. Transcriptome profiling of CD8+ T cells unveiled that C-X-C motif chemokine receptor 6 positive (CXCR6+) CD8+ T cells were recruited into the brain through microglial and astrocyte-derived C-X-C motif chemokine ligand 16 (CXCL16). This recruitment process impaired neurogenesis and induced anxiety-like behaviour via tumour necrosis factor-α-dependent mechanisms. Our findings highlight the role of glial cell derived CXCL16 in mediating the recruitment of CXCR6+CD8+ T cell subsets into the brain. This mechanism represents a potential avenue for modulating hippocampal neurogenesis and emotion-related behaviours after hepatitis B vaccination.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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