Search Results (849)

The lysine methyltransferase SMYD5 is an important regulator of development and has been implicated in multiple malignancies, such as heart disease, lung and gastric cancers, breast and hepatocellular carcinomas, and inflammatory bowel disease. Further, SMYD5 has been linked to the mild hypothermia response, RNA translation, and HIV-1 transcription. SMYD5 is ubiquitously expressed in lymphocytes and the fetal brain, retina, heart, gut, liver, and reproductive organs. Mechanistically, SMYD5 methylates histone residues H3K36, H3K37, and H4K20, as well as non-histone targets such as the ribosomal protein RPL40 and the HIV-1 Tat protein. Here, we review the literature on SMYD5, focusing on its epigenetic functions and its roles in development, cancer, and other biological processes. Full article

Myopia is increasingly recognized as an inflammatory ocular disease. Vitamin D₃ is a potential modulator of the gut–eye axis, but its role in inflammation-induced myopia remains unclear. This study investigated whether vitamin D₃ supplementation attenuates myopia progression by regulating retinal inflammation, gut microbiota composition, and microbiota-derived metabolites in a TGF-β2–induced myopia model. Three-week-old Brown Norway rats received weekly periocular TGF-β2 injections with or without daily oral vitamin D₃, and myopia development was evaluated on days 1 and 21 by axial length and refractive error. Cecal contents were analyzed for α- and β-diversity and taxonomic differences, and day-21 serum underwent untargeted metabolomic profiling of microbiota-derived metabolites, including bile acids and imidazole derivatives; Spearman correlation linked microbial or metabolic alterations with myopia progression. TGF-β2 induced axial elongation, myopic refractive shifts, and upregulated retinal pro-inflammatory cytokines (p-NFκB, IL-1β, TNF-α), while vitamin D₃ supplementation markedly attenuated myopia progression and retinal inflammation. Cecal α-diversity did not differ among control, vitamin D₃, TGF-β2, and TGF-β2+vitamin D₃ groups, but vitamin D₃ significantly reshaped β-diversity and reduced the Firmicutes/Bacteroidota ratio. Distinct metabolite profiles were observed, with the vitamin D₃ group showing reduced hyodeoxycholic acid and elevated imidazole derivatives (imidazolepropionic and methylimidazoleacetic acids). Vitamin D₃ supplementation attenuated myopia progression by reducing retinal inflammation and concurrently reshaping the gut microbiome and its metabolites compared to the control and myopic groups. These results underscore the potential of vitamin D₃ to modulate the gut–retina axis as a nutritional approach for mitigating myopia development. Full article

Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of −23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway. Full article

Diabetic retinal disease (DRD) has classically been defined as a microvascular complication of diabetes; however, the recent evidence highlighted the key role of neuronal degeneration during the earliest stages of its pathogenesis. Therefore, neuroprotection has emerged as a promising therapeutic strategy to prevent disease progression. Topical administration via eyedrops represents a non-invasive approach to deliver neuroprotective agents directly to the retina. This review summarizes the current advances in the field of neuroprotective therapies against early DRD with a special focus on topical delivery, including preclinical and clinical evidence, while discussing the relevance of the transscleral route of absorption in all of them. In this review, the most promising neuroprotective compounds under development will be discussed, highlighting the opportunity that they represent for treating early stages of DRD. Full article

Background/Objectives: Optical coherence tomography (OCT) and OCT angiography (OCT-A) provide detailed measurements of retinal structure and vasculature; however, age-related differences in how these parameters correlate with one another remain poorly understood. We hypothesized that vascular–structural integration in the macula is more pronounced in adults than in children. Our aim was to characterize correlation patterns in pediatric and adult populations to inform the development of age-specific clinical interpretation guidelines. Methods: This prospective cross-sectional observational study enrolled 37 healthy children (age 1–17 years) and 28 healthy adults (age 18–65 years). Eyes with ocular or systemic conditions affecting the retina or prior intraocular surgery were excluded. Standardized OCT and OCT-A acquisition protocols provided structural and vascular measures. Univariable correlation analyses applied a stringent threshold (p < 0.001) to identify robust associations. Significant univariable results were entered into multivariable regression models adjusting for age, gender, intraocular pressure, and axial length. A Group-wise Linkage Proportion quantified the percentage of potential significant correlations among eight predefined anatomical parameter groups. Results: Ninety univariable correlations met p < 0.001. Fourteen correlations were shared across age groups, notably foveal avascular zone metrics and vessel density, showing very large negative correlations (r = −0.70 to −0.87). The pediatric cohort displayed 40 unique correlations, primarily linking optic nerve head flow indices to retinal nerve fiber layer thickness. Adults exhibited 36 unique correlations, dominated by macular vascular–thickness coupling concentrated in the parafoveal region. After multivariable adjustment, 52 of 90 associations remained significant. Adult-specific associations lost significance more frequently (58%) than pediatric-specific associations (43%), whereas correlations shared across both groups showed complete stability (100%). The Group-wise Linkage Proportion indicated pronounced macular vascular–structural coupling in adults (48.4%) versus near absence in children (1.2%). Conclusions: Retinal parameter correlation patterns show fundamental differences between pediatric and adult eyes. While optic nerve head-macular thickness relationships remain consistent across ages, adults exhibit mature, localized integration of macular vascular and structural parameters absent in children. These findings suggest that pediatric and adult OCT/OCT-A measurements may benefit from separate reference standards, although prospective validation is required before clinical implementation. Full article

Diabetes mellitus represents a major global health challenge with rapidly increasing prevalence and substantial morbidity driven by metabolic and vascular complications. Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and are increasingly implicated in the pathogenesis and progression of diabetes. This review summarizes current knowledge on EV biology, including their classification, cellular sources, biogenesis, uptake mechanisms, and molecular cargo. We discuss the contribution of EV-associated microRNAs to immune dysregulation and β-cell damage in type 1 diabetes mellitus (T1DM), as well as the role of EVs in insulin resistance, metabolic signaling, and vascular dysfunction in type 2 diabetes mellitus (T2DM). Particular emphasis is placed on EV-mediated modulation of endothelial function, angiogenesis, and tissue repair, alongside their involvement in the impairment of insulin receptor integrity. We further explore how lifestyle factors may influence EV composition and function, highlighting their potential integration into preventive strategies. Finally, we evaluate the emerging therapeutic potential of EVs as biomarkers and delivery systems, while addressing current limitations and future directions. Collectively, EVs represent a promising frontier in understanding diabetes pathophysiology and developing innovative diagnostic and therapeutic approaches. Unlike previous reviews that examine EVs separately as biomarkers or therapeutic vehicles, this review integrates emerging evidence supporting EVs as mediators of systemic communication linking pancreatic islets, adipose tissue, immune cells, vascular endothelium, kidney, heart, and retina throughout diabetes progression. We further critically evaluate translational barriers that currently limit clinical implementation of EV-based diagnostics and therapeutics. Full article

This study investigated retinal interspecific differences between two sympatric lizards from the Turpan Basin of Xinjiang that occupy distinct microhabitats. Eremias roborowskii inhabits shrublands, while Phrynocephalus axillaris lives in open sandy areas. We adopted retinal whole-mounting, paraffin sectioning, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) to compare retinal structure, oil droplet traits, photoreceptor arrangement, and ultrastructural characteristics between the two species. Both species exhibited five types of colored oil droplets, a temporal fovea, and a highly vascularized conus papillaris, confirming cone-dominant retinas. P. axillaris had larger oil droplets with an average diameter of 3.719 ± 1.100 μm. In contrast, E. roborowskii showed a higher oil droplet density of 1473 ± 1203 ind/mm². The inner plexiform layer (IPL) was significantly thicker in E. roborowskii (56.01 ± 14.76 μm) relative to P. axillaris (50.76 ± 15.25 μm). The two species also differed markedly in photoreceptor ultrastructure. E. roborowskii contained mitochondria-rich ellipsoids, while P. axillaris possessed glycogen-enriched paraboloids. These structural variations reflect compatibility with local ambient light conditions. E. roborowskii is predisposed to suit diffuse shrubland light through high droplet density and mitochondrial-dominant ellipsoids, whereas P. axillaris tends to accommodate intense open-field sunlight via larger oil droplets and well-developed paraboloids. This study provides key morphological evidence to reveal how microhabitat divergence drives retinal specialization among desert reptiles. Full article

Photonic imaging technologies have profoundly transformed neuro-ophthalmic diagnostics by enabling non-invasive visualization of neurodegenerative processes at the retinal level. This review examines how advanced light-based modalities provide unprecedented insights into the structural, physiologic, and biologic relationships between the eye and brain in conditions such as optic neuritis, multiple sclerosis, and glaucoma. Optical coherence tomography has emerged as an essential tool for quantifying thinning of the retinal nerve fiber layer and ganglion cell layer, serving as reliable biomarkers of axonal loss and disease progression across multiple sclerosis subtypes and optic neuropathies. Detection of apoptosing retinal cells imaging enables real-time visualization of retinal ganglion cell apoptosis preceding irreversible structural damage, offering a critical window for early intervention in various neurodegenerative conditions, in particular, glaucoma. Two-photon microscopy with adaptive optics enables subcellular-resolution imaging of retinal neurons, microvascular dynamics, and inflammatory processes in vivo, facilitating the characterization of neurodegenerative mechanisms at unprecedented spatial scales and redefining neuro-ophthalmology by positioning the retina as an accessible extension of the central nervous system. This review critically examines how established and investigational photonic imaging modalities may support earlier disease detection, longitudinal monitoring, and biomarker development in neuro-ophthalmic and neurodegenerative disorders, with potential implications for more timely and targeted management strategies. Full article

Circadian regulation has emerged as an important modulator of ocular growth; however, its role in organizing retina–choroid transcriptomic responses during myopia development remains incompletely understood. In this study, we reanalyzed publicly available retinal and choroidal RNA-seq datasets from chick models of form-deprivation myopia using a multistage machine learning framework. A biologically motivated ZT8/12 circadian window was defined from prior published time-of-day transcriptomic evidence and evaluated using feature selection, cross-tissue and cross-stage validation, and external validation in an independent retinal dataset. Machine learning models classified the ZT8/12 window with high performance across onset and progression datasets, and control analyses indicated that this signal reflects a broad transcriptome-wide temporal state rather than a pattern unique to the 53-gene signature. The final gene signature is therefore interpreted as a stable representative subset of the ZT8/12-associated expression state. Cross-species functional enrichment and ortholog mapping suggested hypothesis-generating functional relationships between chicken genes and human orthologs. Overall, this work provides a computational framework for evaluating time-associated expression patterns in myopia and highlights circadian timing as a candidate component of retina–choroid biology requiring further functional validation. Full article

Glaucoma is a complex condition with an unknown exact cause, but it involves progressive damage to the optic nerve. This damage is primarily driven by high eye pressure, poor blood flow, and oxidative stress, a process linked to cell ageing and inflammation that harms the retina. Recent research highlights that these issues stem from structural changes in the eye’s drainage system and visual pathways, which can be analysed through the lens of engineering thermodynamics. This study proposes a thermal explanation for the physiological processes linking ocular behaviour to inflammatory ion flux alterations. We develop a thermal model demonstrating that temperature increases are tied to the mechanical work necessary for maintaining water flux in the anterior ocular chamber. We show that these changes alter the membrane potential and tissue pH, resulting in elevated intraocular pressure. By clarifying the temperature–pressure effect, this research establishes a theoretical framework to study the developments of future glaucoma therapies. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual impairment. Optical coherence tomography (OCT) has revolutionized the diagnosis and monitoring of AMD by enabling in vivo visualization of retinal microstructure and identification of imaging biomarkers associated with progression to late-stage disease. Improved understanding of these lesions may clarify disease pathogenesis and inform the development of new therapeutic strategies and clinical trial endpoints. This review summarizes OCT-based biomarkers reported as predictors of progression to late atrophic forms of AMD, with emphasis on early atrophic changes that precede GA. Full article

Background/Objectives: Inflammation is a critical contributor to the development of diabetic retinopathy (DR). In the early stages of DR, the compromised permeability of the blood–retina barrier facilitates the infiltration of macrophages and the activation of microglia. These specific retinal immune cells can adopt morphologies M1 or M2, linked to pro- or anti-inflammatory responses, respectively. This dual response represents a new therapeutic target against DR progression. This study aimed to investigate the modulation of the response M1/M2 and the molecular mechanism of two algal diterpenoids, rugukadiol A (RK) and ruguloptone A (RL), in the early inflammatory events associated with DR. Methods: LPS-stimulated microglial (Bv.2) and macrophage (RAW264.7) cells and an ex vivo physiological model of DR were used to analyze the effects of RK and RL on M1 and M2 inflammatory markers. Results: Compounds RK and RL, besides decreasing the expression of the M1 pro-inflammatory factors iNOS, Il6 mRNA, and NLRP3 in LPS-stimulated Bv.2 cells, caused enhancements in Arg-1 mRNA and Il10 mRNA expression consistent with the induction of an M2 anti-inflammatory response. RK promoted p38α-MAPK phosphorylation, suggesting a non-classical activation of p38α related to the induction of anti-inflammatory responses. Consistently, treatment of retinal explants of BB rats in the early stages of DR with RL decreased M1 pro-inflammatory mediators and induced M2 anti-inflammatory markers, with a reduction in gliosis and a phenotype switch from activated to resting microglia. Conclusions: This study provides the first evidence of algal diterpenoids attenuating pro-inflammatory mediators and promoting the resolution of inflammation in a diabetic retinopathy context, thus opening the way to further explore this class of marine natural products and analogs for early DR management. Full article

While diabetic retinal disease (DRD) has classically been viewed as a microvascular complication, emerging evidence places the photoreceptor at the center of its pathogenesis. Recognizing this central role provides a critical framework for resolving a major clinical paradox in diabetes: why the retina exhibits profound susceptibility to hyperglycemic damage, whereas closely related neural tissues like the brain are mostly spared. In this review, we synthesize the evidence for photoreceptor-driven DRD pathology by evaluating two primary mechanistic paradigms. In the first, hyperglycemia-induced damage to the blood vessels limits perfusion, creating an ischemic environment that selectively devastates tissues dependent on exceptionally high blood flow and energy delivery—specifically, the photoreceptors. In the second paradigm, hyperglycemia induces a direct shift in the metabolic profile of photoreceptors, triggering oxidative stress and dysregulated lipogenesis that subsequently place pathological strain on the local microvasculature. Regardless of whether the initial insult is vascular or neuronal, the photoreceptor remains the critical node of disease progression. Because current and investigational DRD treatments predominantly target downstream vascular consequences, exploring these dual mechanisms highlights an urgent need and a significant opportunity to develop novel therapies that target the photoreceptor to address DRD at its root. Full article

Background/Objectives: Color vision deficiency (CVD) arises from the absence or dysfunction of one or more cone photoreceptors in the retina, resulting in impaired color discrimination. Although inherited CVD cannot be cured, optical compensation strategies such as color-filtering glasses have been developed to enhance color perception. However, quantitative clinical evaluations of their corrective efficacy remain limited. This study aimed to assess the effectiveness of notch filter-based color blind glasses in improving color perception and discrimination in individuals with CVD. Methods: Notch filters were employed as color correction lenses, and clinical assessments were conducted to evaluate their impact on human color perception. Subjects underwent standardized color vision tests, including the Color Bridge test, Farnsworth-Munsell 100 Hue test, and D-15 panel test, both before and after wearing the glasses. Outcomes were quantitatively analyzed using total error score (TES), confusion angle, and confusion index (C-index) to determine changes in color discrimination performance. Results: Quantitative analysis demonstrated that wearing the notch filter glasses amplified color differences along confusion lines. In clinical trials, 83% of subjects showed improved color discrimination in the F-M 100 Hue test, with TES reductions between 6.67% and 50.00%. Furthermore, D-15 panel testing revealed that 67% of participants exhibited a decreased C-index and reduced scatter index (S-index), with specific cases shifting from deficient to normal color perception (C-index < 1.6). These results indicate that the filters effectively mitigate symptoms of color vision deficiency by increasing perceptual contrast. Conclusions: Notch filter-based color correction glasses can enhance chromatic discrimination in individuals with CVD by increasing perceptual color contrast. These findings provide practical insights for the optimization and fabrication of color vision correction eyewear utilizing spectral notch filtering strategies. Full article