Qinghua Peng

Reduced tear output can arise from altered neural regulation, impaired epithelial secretion, or loss of secretory tissue, with different implications for recovery. This focused narrative review integrates physiological, single-cell, spatial, organoid, and mechanistic studies identified through a structured PubMed search and targeted reference checking. We examine how remodeling of the lacrimal secretory niche affects acinar secretory competence, the capacity of viable acinar cells to convert stimulation into coordinated fluid, electrolyte, and protein secretion. Omics studies identify disease-associated expression patterns and candidate interactions, while selected perturbation studies link neural, inflammatory, and metabolic mechanisms to secretory dysfunction. We use residual functional reserve as a working concept for secretion that surviving tissue and its supporting niche can recruit through stimulation or relief of suppression. Potentially reversible functional suppression, persistent niche dysfunction, and structural failure describe overlapping constraints on secretion, not validated disease stages. These descriptions are distinct from the cellular, glandular, and lacrimal functional-unit levels at which outcomes are measured. The framework organizes questions about mechanism and recovery but does not establish a clinical treatment algorithm. Progress requires functional testing of candidate mechanisms and assessment of recovery at the level relevant to each claim.

Retinal neurodegenerative diseases (RNDs) represent a major group of disorders leading to irreversible visual impairment. Persistent oxidative stress, mitochondrial dysfunction, inflammatory responses, lipid peroxidation, and disruption of neurovascular unit homeostasis are closely implicated in retinal neuronal and vascular injury. Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream effector heme oxygenase-1 (HO-1) constitute a key regulator y axis in cellular antioxidant defense and adaptive stress responses. Current preclinical evidence suggests that Nrf2/HO-1 signaling may participate in retinal cytoprotection, inflammatory regulation, and maintenance of neurovascular homeostasis in RNDs by modulating redox homeostasis and interconnected injury responses. This review critically synthesizes the cytoprotective roles, evidence boundaries, translational challenges, and future directions of Nrf2/HO-1 signaling in RNDs, organized around retinal cell types, redox homeostasis-related injury mechanisms, disease-specific evidence, and intervention strategies. Further translation will require stronger causal validation, improved ocular delivery, and better cell type-specific targeting.

Background: Dry eye disease (DED) and anxiety are prevalent disorders that often coexist, yet the molecular mechanisms underlying their comorbidity remain inadequately understood. This study sought to elucidate the convergent genes, pathways, and immune signatures that link DED and anxiety by employing integrated bioinformatics and experimental validation approaches. Methods: Datasets (GSE44101, GSE98793) were retrieved from the GEO database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and LASSO regression were utilized to identify candidate genes associated with comorbidity. Subsequently, functional enrichment analysis, protein–protein interaction network analysis, immune infiltration deconvolution, and single-cell RNA sequencing were conducted. A comorbid DED-anxiety mouse model was developed using a combination of desiccating stress, 0.2% benzalkonium chloride, and chronic unpredictable mild stress. The expression of hub genes was validated through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blotting. Results: Researchers identified 128 candidate genes enriched in pathways like circadian rhythm. Four key genes ( BTBD1 , BANK1 , UBA3 , NEDD1 ) were highlighted for their expression in corneal epithelium cells. Immune analysis linked these genes to plasma cells and B cell subsets. In a mouse model, symptoms of dry eye, anxiety, inflammation, and neurotransmitter imbalance were observed, with the hub genes upregulated. RT-qPCR and Western blot analyses confirmed significant upregulation of BTBD1 , BANK1 , UBA3 , and NEDD1 in corneal tissues, while in the lacrimal gland and hippocampus, BANK1 was elevated but BTBD1 , UBA3 , and NEDD1 were downregulated, indicating tissue-specific regulatory patterns. Conclusion: The study suggests BTBD1 , BANK1 , UBA3 , and NEDD1 are linked to immune-inflammatory features in DED-anxiety comorbidity, with distinct tissue-specific expression profiles observed across the cornea, lacrimal gland, and hippocampus, offering a basis for future research into shared pathways.

Dry eye disease (DED) exposes the ocular surface to persistent hyperosmolar, oxidative, metabolic, and inflammatory stress that may increase susceptibility to ferroptosis. Whether autophagy promotes or limits ferroptotic injury in DED remains unresolved. This review critically evaluates evidence from corneal and conjunctival epithelia, lacrimal glands, and meibomian glands, using non-ocular models only to interpret mechanisms not yet resolved in ocular tissues. We propose a threshold-balance framework in which autophagy has context-dependent effects. Ferritinophagy, lipophagy, and impaired autophagic flux can expand the labile iron pool, mobilize peroxidizable lipids, and promote lipid peroxidation. Conversely, intact autophagic–lysosomal flux and mitophagy can remove damaged cargo, limit mitochondrial oxidative stress, and preserve membrane antioxidant defenses. The balance between these processes may determine whether stressed ocular-surface cells adapt or progress toward ferroptotic injury, with consequences for epithelial barrier integrity, tear-film homeostasis, glandular secretion, and inflammation. Studies combining autophagy-related pathway perturbation with ferroptosis-related outcomes are concentrated in ocular-surface epithelial models, whereas this relationship has been less directly examined in lacrimal and meibomian tissues. Establishing causality will require flux-aware measurements, targeted pathway perturbation, tissue-resolved models, and functional validation in human samples. Such studies should clarify when and where autophagy–ferroptosis crosstalk is therapeutically actionable in DED.

Retinal degeneration is characterized by progressive photoreceptor loss driven by oxidative stress and chronic inflammation, yet effective mutation-independent therapeutic strategies remain limited. Lycium barbarum polysaccharides (LBPs) possess antioxidant and anti-inflammatory activities; however, the structural features responsible for their retinal protective effects remain poorly defined. In this study, crude LBP was fractionated by DEAE-cellulose ion-exchange chromatography, and the most bioactive fraction, LBPF2, was identified using H₂O₂-injured 661W cone photoreceptor-like cells. LBPF2 was subsequently characterized by high-performance anion-exchange chromatography, SEC-MALLS-RI, GC–MS methylation analysis, and one- and two-dimensional NMR spectroscopy, and its protective effects were evaluated in H₂O₂-treated 661W cells and rd10 mice. LBPF2 was identified as a homogeneous glucose-rich polysaccharide with an average molecular weight of approximately 41 kDa and a backbone mainly composed of →4)-α-D-Glcp-(1→ and →4,6)-α-D-Glcp-(1→ residues. LBPF2 reduced oxidative stress, inflammation, and apoptosis in H₂O₂-treated 661W cells, preserved retinal morphology, improved electroretinographic responses and partial retention of rhodopsin immunoreactivity relative to untreated rd10 mice, and restored redox homeostasis in rd10 mice. Pharmacological inhibition of Nrf2 using ML385 attenuated these protective effects, supporting the involvement of Nrf2/HO-1 signaling. Collectively, these findings identify LBPF2 as a structurally characterized neuroprotective polysaccharide that mitigates retinal degeneration through coordinated regulation of oxidative stress and inflammation and highlight its therapeutic potential for retinal degenerative diseases.

Dietary polysaccharides are important bioactive components of functional foods and play a key role in modulating host metabolism through interactions with the gut microbiota. Lycium barbarum polysaccharides (LBP) are widely consumed as dietary supplements; however, their nutritional relevance in linking gut microbiota–associated metabolic regulation to extra‐intestinal tissue homeostasis remains incompletely understood. In this study, we investigated the effects of dietary LBP intake on gut microbiota composition, metabolic profiles, and retinal redox status using oxidatively stressed 661W photoreceptor cells and rd10 mice. In vitro, LBP exposure was associated with reduced intracellular reactive oxygen species accumulation and enhanced cellular antioxidant capacity under oxidative stress conditions. In vivo, dietary LBP intake was associated with partial preservation of retinal structural parameters, including outer nuclear layer thickness and retinal vascular features. Integrated 16S rRNA gene sequencing and untargeted metabolomics analyses demonstrated that dietary LBP intake was associated with coordinated modulation of gut microbiota composition and microbial‐derived metabolic pathways, particularly those related to pantothenate and coenzyme A biosynthesis, aromatic amino acid metabolism, and aminoacyl‐tRNA biosynthesis. These metabolic alterations were reflected in retinal metabolic profiles and accompanied by improved redox balance. Overall, this study highlights the nutritional significance of LBP as a functional polysaccharide and supports the concept that dietary modulation of gut microbiota–associated metabolism may contribute to maintaining retinal metabolic homeostasis. These findings provide a nutritional and food science perspective on the potential role of dietary polysaccharides in supporting tissue function beyond the gastrointestinal tract.

Dry eye disease (DED), a prevalent ocular condition, has seen rising incidence rates. Aberrant inflammation and immune dysregulation are key pathogenic fac

Oculomics, the study of the relationship between ophthalmic biomarkers (changes or abnormalities in the eye) and systemic health or disease states, posits that the eye can serve as a window into the overall health of the body. This concept aligns closely with the ideas of traditional Chinese medicine (TCM) ocular diagnosis, which similarly emphasizes the eye as a reflective indicator of systemic conditions. As a burgeoning field, oculomics extends beyond traditional imaging-based approaches to encompass a broader spectrum of ocular biomarkers, including biochemical and electrophysiological data. While retinal imaging has been a cornerstone in identifying structural biomarkers from eyes, the integration of biochemical omics (e.g., metabolomics, proteomics, transcriptomics) and electrophysiological assessments offers a more comprehensive and multidimensional approach to understanding the association of systemic health between disease states. By integrating TCM ocular diagnosis with artificial intelligence, oculomics may offer a more cost-effective diagnostic option due to its non-invasive and economically efficient characteristics. In this review, we proposed a research framework for integrating ocular multimodal biomarkers from the perspectives of ocular imaging, biochemical testing, and electrophysiological assessment, further clarifying the new concept of oculomics. This multimodal approach exhibits significant potential for advancing precision medicine, ultimately improving patient outcomes through early detection and personalized treatment strategies.

Background: Glaucoma is a leading cause of irreversible blindness and is increasingly understood as a chronic neurodegenerative disorder rather than a disease explained solely by elevated intraocular pressure (IOP). Although IOP lowering remains the cornerstone of treatment, many patients continue to progress despite apparently adequate pressure control, indicating that additional mechanisms shape retinal ganglion cell (RGC) vulnerability and disease course. Among these, autophagy and mitophagy have emerged as central regulators of cellular stress adaptation in both anterior and posterior ocular tissues. Main Body: This review argues that glaucoma can be more coherently interpreted through a stage- and compartment-specific framework of autophagy and selective mitophagy. In the conventional outflow pathway, autophagy contributes to mechanoadaptation, proteostasis, and extracellular matrix homeostasis, whereas chronic oxidative and biomechanical stress may impair lysosomal function and autophagic flux, thereby promoting outflow dysfunction and ocular hypertension. In the posterior segment, RGCs and their axons are highly dependent on autophagy for proteostasis and mitochondrial quality control because of their polarized morphology and substantial metabolic demand. Experimental work suggests that autophagy may be protective during early or acute stress but become insufficient, stalled, or maladaptive during chronic injury. Recent human stem cell and animal studies further implicate optineurin-linked autophagic-lysosomal dysfunction, AMPK–mTORC1 imbalance, and reduced PINK1/Parkin-associated mitophagy as mechanistic nodes linking mitochondrial stress to RGC degeneration. These observations support a model in which glaucoma progression reflects not simply more or less autophagy, but failure to maintain effective quality control across distinct ocular compartments and disease stages. Conclusion: A compartment-aware and time-resolved view of autophagy and mitophagy offers a more nuanced framework for glaucoma pathogenesis and therapy. Future progress will likely depend less on indiscriminate pathway modulation than on restoring selective, flux-competent quality control, particularly mitochondrial turnover, in the appropriate tissue and at the appropriate stage of disease.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults and is characterized by progressive dysfunction of the retinal pigment epithelium (RPE). Although genetic susceptibility and environmental exposure both contribute to disease risk, the mechanisms through which chronic metabolic and oxidative stress are integrated into sustained RPE dysfunction remain incompletely understood. Increasing evidence from human AMD donor tissue and experimental RPE models indicates that epigenetic regulation operates at the interface between mitochondrial dysfunction, redox imbalance, and transcriptional remodeling. This review synthesizes current findings on DNA methylation, chromatin accessibility, histone modification, and RNA-based regulation in AMD, with emphasis on their metabolic and mitochondrial context. Studies in human AMD-RPE demonstrate that epigenetic alterations are generally selective rather than global and frequently involve pathways related to mitochondrial maintenance, lipid metabolism, oxidative stress responses, and cellular homeostasis. Mechanistically, mitochondrial dysfunction and reactive oxygen species (ROS) may influence epigenetic regulation through altered Nicotinamide adenine dinucleotide (NAD⁺) availability, acetyl-CoA metabolism, redox-sensitive chromatin regulation, and modulation of DNA methyltransferase and histone deacetylase activity. Redox-sensitive pathways, including antioxidant signaling, further connect mitochondrial stress to adaptive or maladaptive transcriptional responses in the RPE. Importantly, while several interactions discussed are supported by findings in human AMD tissue, other components of the proposed epigenetic–mitochondrial–redox framework remain inferential or model-based and require further validation. Rather than acting as isolated disease triggers, epigenetic changes are more likely to function as stress-responsive regulatory layers that stabilize transcriptional states over time in a long-lived post-mitotic tissue. We further discuss unresolved questions regarding causality, reversibility, therapeutic feasibility, and stage-specific intervention strategies. Collectively, this framework positions the epigenetic–mitochondrial–redox axis as a unifying model for understanding RPE vulnerability and AMD progression.