Search Results (137)

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management. Full article

Acid mine drainage (AMD) environments feature extreme acidity (pH ≤ 2) and high heavy metal concentrations. Acidophiles survive these conditions through unique genetic adaptations and secondary metabolite (SM) pathways. Leptospirillum ferriphilum, known for its acid and heavy metal resistance, serves as a model for AMD bioremediation, though systematic multi-omics studies on its key SMs and biosynthesis pathways remain underexplored. In this study, L. ferriphilum YR01 was isolated and identified from the AMD of the Zijinshan copper mine, China. Pangenomic analysis revealed that YR01 possesses the largest number of genes (2623) among the eight sequenced L. ferriphilum strains. Comparative genomics, antiSMASH, BiG-SCAPE, and metabolomic analyses (LC-MS and HPLC-MS) were integrated to comprehensively explore its biosynthetic capacity. A total of 39 biosynthetic gene clusters (BGCs) were identified, of which 60% shared <50% similarity with known clusters, indicating substantial novel biosynthetic potential. The sequence alignment of SM biosynthetic gene clusters (BGCs) demonstrated the potential of L. ferriphilum to synthesize conserved clusters for ectoine, choline, carotenoids, terpenoids, and terpene precursors. YR01 harbors complete BGCs for all five SM types. Notably, key nonribosomal peptide synthetase (NRPS) modules implicated in N-acyl homoserine lactone (AHL) synthesis were identified. Untargeted metabolomics (LC-MS) revealed the production of diverse SMs (18 types) putatively involved in environmental adaptation, including phosphocholine, carotenoids (e.g., anteraxanthin), cholera autoinducer-1 (CAI-1), and multiple AHLs. Targeted detection (HPLC-MS) further confirmed that YR01 could produce ectoine (0.10 ng/mL) and specific AHLs (C₁₄-HSL, C₁₂-HSL, C₁₂-OH-HSL), which were beneficial for the survival of the strain in extremely acidic environments and interspecies communication through SMs. This study represents the first comprehensive multi-omics characterization of BGCs in L. ferriphilum and experimentally validates the production of key SMs. Collectively, this study provides a comprehensive elucidation of the SM biosynthetic repertoire and environmental adaptation strategies in L. ferriphilum, advancing our understanding of microbial adaptation and interspecies communication in AMD systems, and offering potential implications for biomining applications. Full article

Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic and molecular pathways involved in eye disorders. In addition to their potential in therapy, RNA technologies have also provided tools for mechanistic studies to improve the understanding of eye diseases, expanding the possibilities of RNA-based treatments. Despite the utility of RNA in studying eye disease mechanisms and its potential in disease treatment, only a few RNA-based therapies have been approved for posterior eye diseases. This paper reviews RNA interference and related ocular delivery and posterior eye diseases, focusing on the use of RNA aptamers, siRNA, short hairpin RNA (shRNA), and microRNA (miRNA). Approaches using RNA to advance our understanding of eye diseases and disease treatments, particularly in the posterior segment of the eye, are discussed. It is concluded that RNA therapeutics offer a novel approach to treating a variety of eye diseases by targeting their molecular causes. siRNA, shRNA, miRNA, and ASO can directly silence disease-driving genes, while RNA aptamers bind to specific targets. Although many RNA-based therapies are still in experimental stages, they hold promise for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, and inherited retinal disorders. Effective delivery methods and long-term safety are key challenges that need to be addressed for these treatments to become widely available. Full article

The widespread use of antimicrobial drugs (AMDs) in livestock production contributes to antimicrobial resistance (AMR), a global One Health concern affecting humans, animals, and the environment. This study analyzed AMD residues and the AMR profiles in Escherichia coli and Enterococcus spp./Streptococcus spp. (ES) isolated from lagoon water samples collected from nine California dairies. Antimicrobial susceptibility testing was performed using the microbroth dilution method, and enzyme-linked immunosorbent assay (ELISA) kits were used to detect AMD residues in lagoon water. Overall, residues of florfenicol and tilmicosin were detected in more than 90% of the samples, while tetracycline was detected in 74.2 ± 4.6% of the samples. In contrast, penicillin and sulfamethazone residues were low, observed in only 3.4 ± 1.9% and 32.3 ± 5.0% of samples, respectively. The very low prevalence of penicillin was likely due to limited use in dairy cattle, given its prolonged withdrawal period. Prevalence estimates for AMR in the lagoon samples showed 100% resistance of E. coli to tiamulin, tilmicosin or tylosin and high prevalence against florfenicol (96.0% ± 2.0) or gamithromycin (92.0% ± 1.9). However, low AMR estimates (less than 10%) were observed against other AMDs tested. Similarly, the prevalence estimates for AMR of ES isolates in the studied lagoon were high against florfenicol (95.1% ± 2.0), tildipirosin (97.6% ± 1.7), or tilmicosin (98.8% ± 1.2), but low against ampicillin (4.9% ± 1.9) and penicillin (8.5% ± 2.4). Despite numerical differences in AMR prevalence by season, region, and sampling point, these variations were not statistically significant. Logistic regression models were applied to explore associations between AMD residues and AMR phenotypes where appropriate. Tilmicosin residues were significantly associated with reduced resistance to danofloxacin, enrofloxacin, and tildipirosin in E. coli isolates, while sulfamethoxazole residues were linked to increased tetracycline resistance in Enterococcus spp. The presence of florfenicol residues, potentially originating from treated calves and heifers, helps explain the high prevalence of resistance to this drug in both bacterial species. However, not all AMD residues were associated with AMR, underscoring the complex ecological and genetic factors involved in the development and maintenance of resistance in dairy environments. These findings underscore the importance of integrating AMR surveillance and prudent AMD use practices across all segments of dairy production systems. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by progressive degeneration of the retinal pigment epithelium (RPE) and photoreceptors in the macula. Current treatment options primarily focus on slowing disease progression in neovascular AMD, while effective therapies for dry AMD remain limited. Optogenetics, a revolutionary technique utilizing light-sensitive proteins (opsins) to control the activity of genetically targeted cells, has emerged as a promising therapeutic strategy for restoring vision in retinal degenerative diseases. In retinal disease models, adeno-associated viruses (AAVs) serve as delivery vectors via intravitreal or subretinal injections. This review explores the principles of optogenetics, its application in preclinical AMD models, and the potential for clinical translation of this approach. We discuss the various optogenetic tools, delivery methods, and the challenges and future directions in harnessing this technology to combat AMD-related vision loss. Full article

Age-related macular degeneration (AMD) is a common eye disease that significantly affects daily activities and impedes the quality of life in aging adults, yet effective treatments to halt or reverse disease progression are currently lacking. Ongoing research aims at understanding the complex mechanisms underlying AMD pathophysiology involving retinal pigment epithelium (RPE) dysfunction, drusen formation, inflammation, neovascularization, and RPE/photoreceptor degeneration. Sigma 2 receptor/transmembrane protein 97 (σ₂R/TMEM97) is a multifunctional protein implicated in cellular processes including cholesterol homeostasis, lysosome-dependent autophagy, calcium homeostasis, and integrated stress response (ISR). Recent genome-wide association studies (GWASs) have identified σ₂R/TMEM97 as a novel genetic risk factor strongly associated with AMD development. In this review, we summarize recent research progress on σ₂R/TMEM97 in age-related neurodegenerative diseases, highlighting its implication as a molecular target in AMD via regulating oxidative stress, inflammation, lipid uptake, drusen formation, and epithelial–mesenchymal transition (EMT). We also discuss the potential of modulating σ₂R/TMEM97 function with novel small-molecule drugs as a promising treatment for dry AMD and the unresolved questions in understanding the mechanistic basis of their actions. Full article

There is growing interest in the use of natural plant-derived compounds, such as polyphenols (including curcumin), flavonoids, silymarin, anthocyanins, lutein, and zeaxanthin, for the treatment of age-related macular degeneration (AMD). These substances exhibit antioxidant, anti-inflammatory, and protective effects on retinal cells, contributing to the preservation of retinal integrity by modulating the key pathogenic mechanisms of AMD, including oxidative stress, chronic inflammation, and pathological neovascularization. Consequently, they hold potential to support conventional therapeutic approaches and slow disease progression. Current studies highlight their promising role as adjunctive agents in AMD management. This literature review provides a comprehensive analysis of the potential role of the aforementioned natural plant-derived compounds in the prevention and supportive treatment of age-related macular degeneration. It also discusses their natural sources, modes of administration and supplementation, and highlights the importance of a nutrient-rich diet as a key factor in maintaining ocular health. Furthermore, the review synthesizes current scientific knowledge on the ability of natural antioxidants to slow the progression of AMD and outlines future research directions aimed at improving diagnostic methods and developing more effective preventive and therapeutic strategies. Full article

Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene–environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue. Full article

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Predicting its progression is crucial for preventing late-stage AMD, as it is an irreversible retinal disease. Both genetic factors and retinal images are instrumental in diagnosing and predicting AMD progression. Previous studies have explored automated diagnosis using single fundus images and genetic variants, but they often fail to utilize the valuable longitudinal data from multiple visits. Longitudinal retinal images offer a dynamic view of disease progression, yet standard Long Short-Term Memory (LSTM) models assume consistent time intervals between training and testing, limiting their effectiveness in real-world settings. To address this limitation, we propose time-varied Long Short-Term Memory (TV-LSTM), which accommodates irregular time intervals in longitudinal data. Our innovative approach enables the integration of both longitudinal fundus images and AMD-associated genetic variants for more precise progression prediction. Our TV-LSTM model achieved an AUC-ROC of 0.9479 and an AUC-PR of 0.8591 for predicting late AMD within two years, using data from four visits with varying time intervals. Full article

Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article

Purpose: We aimed to investigate whether genetic variants susceptible to age-related macular degeneration (AMD) are associated with intraocular inflammation after brolucizumab administration in eyes that have exudative AMD. Methods: A total of 206 eyes from 206 patients (156 men/50 women, 74.0 ± 8.4 years; treatment-naïve, 128 [62.1%]; switching, 78 [37.9%]) were included in this study. All patients were treated with intravitreal brolucizumab at least once. The genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH (rs1329428), SKIV2L (rs429608), C3 (rs2241394), cholesteryl ester transfer protein (CETP) (rs3764261), and ADAMTS9 (rs6795375) was performed using TaqMan technology. Results: Out of the 206 patients who were included, 21 eyes from 21 patients (10.2%) exhibited intraocular inflammation (IOI). Four (19.0%) exhibited severe IOI, including retinal vasculitis and/or retinal vascular occlusion, and 17 (81.0%) showed mild IOI. The frequency of the T allele of the CETP gene was significantly lower in patients who developed IOI compared to patients who did not develop IOI (T allele frequency: 9.5% vs. 23.5%, p = 0.036). After adjusting for confounding factors, the T allele remained significantly associated with protection against IOI (p = 0.028, 95% confidence interval: 0.098–0.88). Conclusions: The T allele of the CETP gene, a risk allele for AMD and the protective allele for atherosclerosis, may be associated with protection against IOI after brolucizumab administration in eyes that have exudative AMD. Full article

Age-related macular degeneration (AMD) is a multifactorial retinal disease influenced by complex molecular mechanisms, including genetic susceptibility, inflammation, oxidative stress, and metabolic dysregulation. While substantial progress has been made in understanding its pathogenesis, the full molecular underpinnings of AMD remain unclear, impeding the effectiveness of current therapeutic strategies. This study provides an in-depth exploration of the molecular interactions involved in AMD progression, particularly focusing on genetic predispositions (such as CFH, ARMS2/HTRA1, and APOE), inflammatory pathways (including complement system dysregulation and cytokine responses), lipid metabolism (e.g., cholesterol homeostasis and drusen formation), and angiogenesis (VEGF signaling). Through a systematic review and bibliometric analysis of literature published between 2015 and 2025, the study identifies emerging research trends, existing gaps, and promising future therapeutic directions. It further investigates innovative precision medicine approaches, including gene editing (CRISPR), RNA therapeutics (siRNA, antisense oligonucleotides), immunomodulatory therapies, and nanotechnology-based drug delivery systems. Additionally, the study examines the role of metabolic disorders such as diabetes and dyslipidemia in AMD progression, highlighting the influence of systemic health factors on disease onset. Finally, the potential of artificial intelligence (AI) in enhancing AMD management through biomarker-based risk stratification, predictive modeling, and personalized treatment optimization is assessed. By mapping the intricate molecular networks underlying AMD and evaluating novel therapeutic strategies, this research aims to contribute to the development of more effective, individualized treatment protocols for patients with AMD. Full article

Accurate power load forecasting is crucial for ensuring grid stability, optimizing economic dispatch, and facilitating renewable energy integration in modern smart grids. However, real load forecasting is often disturbed by the inherent non-stationarity and multi-factor coupling effects. To address this problem, a novel hybrid forecasting framework based on adaptive mode decomposition (AMD) and improved least squares support vector machine (ILSSVM) is proposed for effective short-term power load forecasting. First, AMD is utilized to obtain multiple components of the power load signal. In AMD, the minimum energy loss is used to adjust the decomposition parameter adaptively, which can effectively decrease the risk of generating spurious modes and losing critical load components. Then, the ILSSVM is presented to predict different power load components, separately. Different frequency features are effectively extracted by using the proposed combination kernel structure, which can achieve the balance of learning capacity and generalization capacity for each unique load component. Further, an optimized genetic algorithm is deployed to optimize model parameters in ILSSVM by integrating the adaptive genetic algorithm and simulated annealing to improve load forecasting accuracy. The real short-term power load dataset is collected from Guangxi region in China to test the proposed forecasting framework. Extensive experiments are carried out and the results demonstrate that our framework achieves an MAPE of 1.78%, which outperforms some other advanced forecasting models. Full article

Biological reduction of sulphates has gradually replaced unit chemical processes for the treatment of acid mine drainage (AMD), which exerts a significant environmental impact due to its elevated acidity and high concentrations of heavy metals. Bioremediation is optimally suited for the treatment of AMD because it is cost-effective and efficient. Anaerobic bioremediation employing sulphate-reducing bacteria (SRB) presents a promising solution by facilitating the reduction of sulphate to sulphide. The formed can precipitate and immobilise heavy metals, assisting them in their removal from contaminated wastewater. This paper examines the current status of SRB-based bioremediation, with an emphasis on recent advances in microbial processes, reactor design, and AMD treatment efficiencies. Reviewed studies showed that SRB-based bioreactors can achieve up to 93.97% of sulphate reduction, with metal recovery rates of 95% for nickel, 98% for iron and copper, and 99% for zinc under optimised conditions. Furthermore, bioreactors that used glycerol and ethanol as a carbon source improved the efficiency of sulphate reduction, achieving a pH neutralisation from 2.8 to 7.5 within 14 days of hydraulic retention time. Despite the promising results achieved so far, several challenges remain. These include the need for optimal environmental conditions, the management of toxic hydrogen sulphide production, and the economic feasibility of large-scale applications. Future directions are proposed to address these challenges, focusing on the genetic engineering of SRB, integration with other treatment technologies, and the development of cost-effective and sustainable bioremediation strategies. Ultimately, this review provides valuable information to improve the efficiency and scalability of SRB-based remediation methods, contributing to more sustainable mining practices and environmental conservation. To ensure relevance and credibility, relevance and regency were used as criteria for the literature search. The literature sourced is directly related to the subject of the review, and the latest research, typically from the last 5 to 10 years, was prioritised. Full article

Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, characterized by the accumulation of extracellular drusen deposits within the macula. The pathogenesis of AMD is multifactorial, involving oxidative stress, chronic inflammation, immune system dysregulation, and genetic predisposition. A key contributor to disease progression is the excessive accumulation of reactive oxygen species (ROS), which damage retinal pigment epithelium (RPE) cells and disrupt cellular homeostasis. Additionally, immunosenescence and chronic low-grade inflammation exacerbate AMD pathology, further impairing retinal integrity. Despite ongoing research, effective therapeutic options remain limited, and there is no definitive cure for AMD. This review explores the intricate molecular mechanisms underlying AMD, including the role of oxidative stress, chronic inflammation, and genetic factors in RPE dysfunction. Furthermore, we highlight potential therapeutic strategies targeting these pathways, as well as the emerging role of bioinformatics and artificial intelligence in AMD diagnosis and treatment development. By improving our understanding of AMD pathophysiology, we can advance the search for novel therapeutic interventions and preventative strategies. Full article