Search Results (818)

Light, as one of the most crucial environmental factors, plays an essential role in the growth, physiology, and evolutionary survival of fish. To cope with diverse light conditions in aquatic environments, fish adapt through photosensory systems composed of both visual and non-visual pathways. The retina is a key component of the visual system of fish, capable of converting external optical signals into neural electrical signals, making it crucial for visual formation. During the process of visual signal transduction, opsins serve as the molecular foundation for vision formation. They can be divided into two major categories: visual opsins and non-visual opsins. Among these, melanopsin, as a member of the non-visual opsin family, acts as a key upstream factor in the circadian phototransduction pathway of fish. In this review, we review the adaptability of fish retinal structures to light reception and introduce in detail the gene diversity and relative expression levels of fish opsins. At the same time, we comprehensively describe the molecular mechanism by which fish adapt to changes in the underwater light environment. We also concluded that melanopsin, as a non-imaging photoreceptor, possesses not only core light-sensing functions but also non-imaging visual functions such as circadian rhythm regulation, body coloration changes, and hormone secretion. This review suggests that future research should not only elucidate the physiological functions of melanopsin in fish but also comprehensively reveal the mechanisms underlying the multi-adaptive nature of fish vision across varying light environments. Through these studies, researchers can have a deeper understanding of the physiological regulation mechanism of fish in complex light environments, and then formulate fish light environment management strategies, optimize aquaculture practices, improve economic returns, and promote the development of related fields. Full article

Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood–retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity. Full article

Vision is fundamental to the acquisition of motor, cognitive, and social skills, playing a crucial role in typical development. Early visual impairments are associated with various neurodevelopmental conditions, including Autism Spectrum Disorder (ASD). The (Brain-specific serine/threonine-protein kinase 2, BRSK2) gene has been identified as a high-risk gene for ASD. This study aims to investigate the role of brsk2 in retinal photoreceptor development and visual function in zebrafish. Using behavioral assays, histological analysis, and transcriptomic profiling, we assessed the impact of brsk2 deletion on retinal structure and function. The results showed that brsk2ab^−/− zebrafish larvae exhibited significantly enhanced light perception compared to wild-type (WT) controls. Structural analysis of the retina revealed disruptions in the layered organization, along with up-regulated rhodopsin expression in retinal cells. Additionally, transcriptomic analysis indicated that key opsins and genes involved in visual development and phototransduction pathways were markedly up-regulated following brsk2 deletion. This research highlights the importance of brsk2 in early retinal circuit development and its potential implications for understanding sensory processing deficits in neurodevelopmental disorders. By linking BRSK2 to specific sensory phenotypes, this study addresses a critical gap in knowledge regarding the mechanisms underlying sensory abnormalities in ASD and related conditions. Full article

Background/Objectives: The Rho^P23H/WT mouse line is a commonly used model to study rhodopsin P23H-associated autosomal dominant retinitis pigmentosa. Previous studies in Rho^P23H/WT mice have largely focused on retinal changes occurring at one month of age and later, and have indicated a compensatory thickening of inner retinal layers in response to rod degeneration. However, the effect of disease processes during early postnatal retinal development remains understudied. Methods: In this study, we investigated the retinal response to rod dysfunction during early postnatal developmental ages P8–P24 in our novel Rho^P23H/WT reporter line, RhoP23H.GFP, which expresses green fluorescent protein (GFP) exclusively in cone photoreceptors. Results: Histological analysis revealed no significant difference in retinal thickness in RhoP23H.GFP mice compared to healthy controls at the ages investigated. RhoP23H.GFP retinas initially exhibited a greater mislocalization of rhodopsin to the rod cell bodies at P12, though this mislocalization normalized to wildtype by P24. Most notably, flow cytometry revealed significantly increased cone photoreceptor numbers in P12 (61%), P16 (48%), and P24 (40%) RhoP23H.GFP mice compared to wildtype controls, indicating a possible compensatory response of cone photoreceptors to rod dysfunction. Additionally, cone morphology appeared altered in diseased cones. Conclusions: Our results suggest that cones may undergo a developmental compensatory adaptation in response to rod dysfunction, providing new insights into early disease mechanisms of retinitis pigmentosa. Full article

Background/Objectives: Retinal optical coherence tomography (OCT) is essential for diagnosing ocular diseases, yet developing high-performing multiclass classifiers remains challenging due to limited labeled data and the computational cost of self-supervised pretraining. This study aims to address these limitations by introducing a curriculum-based self-supervised framework to improve representation learning and reduce computational burden for OCT classification. Methods: Two ensemble strategies were developed using progressive masked autoencoder (MAE) pretraining. We refer to this curriculum-based MAE framework as CurriMAE (curriculum-based masked autoencoder). CurriMAE-Soup merges multiple curriculum-aware pretrained checkpoints using weight averaging, producing a single model for fine-tuning and inference. CurriMAE-Greedy selects top-performing fine-tuned models from different pretraining stages and ensembles their predictions. Both approaches rely on one curriculum-guided MAE pretraining run, avoiding repeated training with fixed masking ratios. Experiments were conducted on two publicly available retinal OCT datasets, the Kermany dataset for self-supervised pretraining and the OCTDL dataset for downstream evaluation. The OCTDL dataset comprises seven clinically relevant retinal classes, including normal retina, age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), retinal vein occlusion (RVO), retinal artery occlusion (RAO), and vitreomacular interface disease (VID) and the proposed methods were compared against standard MAE variants and supervised baselines including ResNet-34 and ViT-S. Results: Both CurriMAE methods outperformed standard MAE models and supervised baselines. CurriMAE-Greedy achieved the highest performance with an area under the receiver operating characteristic curve (AUC) of 0.995 and accuracy of 93.32%, while CurriMAE-Soup provided competitive accuracy with substantially lower inference complexity. Compared with MAE models trained at fixed masking ratios, the proposed methods improved accuracy while requiring fewer pretraining runs and reduced model storage for inference. Conclusions: The proposed curriculum-based self-supervised ensemble framework offers an effective and resource-efficient solution for multiclass retinal OCT classification. By integrating progressive masking with snapshot-based model fusion, CurriMAE methods provide high performance with reduced computational cost, supporting their potential for real-world ophthalmic imaging applications where labeled data and computational resources are limited. Full article

Since the 1960s, Grassy Narrows First Nation, Canada, has been exposed to methylmercury (MeHg) from fish consumption following Hg discharge from a chloralkali plant. Prenatal exposure to MeHg is known to affect the neurodevelopment of fetuses and the retina is sensitive to neurodevelopmental damage. The multidisciplinary, cross-sectional Niibin study, developed with Grassy Narrows First Nations, included visual examinations with retinal evaluation using optical coherence tomography (OCT). The present analyses focused on the 59 participants (116 eyes) with umbilical cord Hg measurements, sampled between 1971 and 1992. Associations between cord blood Hg and retinal thickness layers surrounding the optic nerve head (RNFL) and inner macula (GC-IPL) were examined using mixed-effect models. Higher cord blood Hg was significantly associated with reduced thickness of GC-IPL layers across all macular sectors; less pronounced associations were observed for RNFL. A qualitative clinical assessment of the OCT results showed that persons with cord blood Hg concentrations ≥ 5.8 µg/L were more likely to present bilateral abnormal retinal thinning (OR = 3.51; [95% CI: 1.06–11.53]). These findings suggest that, in this Indigenous community, prenatal MeHg exposure may have enduring effects on retinal thickness and underline the importance of OCT technology in providing tailored eye care. Full article

With the rapid development of remote sensing technology and deep learning, the port ship detection based on a single-stage algorithm has achieved remarkable results in optical imagery. However, most of the existing methods are designed and verified in specific scenes, such as fixed viewing angle, uniform background, or open sea, which makes it difficult to deal with the problem of ship detection in complex environments, such as cloud occlusion, wave fluctuation, complex buildings in the harbor, and multi-ship aggregation. To this end, ES-YOLO framework is proposed to solve the limitations of ship detection. A novel edge perception channel, Spatial Attention Mechanism (EACSA), is proposed to enhance the extraction of edge information and improve the ability to capture feature details. A lightweight spatial–channel decoupled down-sampling module (LSCD) is designed to replace the down-sampling structure of the original network and reduce the complexity of the down-sampling stage. A new hierarchical scale structure is designed to balance the detection effect of different scale differences. In this paper, a remote sensing ship dataset, TJShip, is constructed based on Gaofen-2 images, which covers multi-scale targets from small fishing boats to large cargo ships. The TJShip dataset was adopted as the data source, and the ES-YOLO model was employed to conduct ablation and comparison experiments. The results show that the introduction of EACSA attention mechanism, LSCD, and multi-scale structure improves the mAP of ship detection by 0.83%, 0.54%, and 1.06%, respectively, compared with the baseline model, also performing well in precision, recall and F1. Compared with Faster R-CNN, RetinaNet, YOLOv5, YOLOv7, and YOLOv8 methods, the results show that the ES-YOLO model improves the mAP by 46.87%, 8.14%, 1.85%, 1.75%, and 0.86%, respectively, under the same experimental conditions, which provides research ideas for ship detection. Full article

This narrative review of rapid eye movement (REM) focuses on its primary etiology and how it fits into the larger framework of neurophysiology and general physiology. Arterial blood flow in the retina may be sensitive to the full overlying ‘weight’ of its adjacent and contiguous vitreous humor caused by the humoral mass effect in the Earth’s gravitational field. During waking hours of the day, this ‘weight’ is continuously shifted in position due to changing head position and eye movements associated with ordinary environmental observations. This reduces its impact on any one point on the retinal field. However, during sleep, the head may maintain a relatively constant position (often supine), and observational eye movements are minimal, leaving essentially one retinal area exposed at the ‘bottom’ of each eye, relative to gravity. During sleep, REM may provide a mechanism for frequently repositioning the retina with respect to the weight it incurs from its adjacent (overlying) vitreous humor. Our findings were consistent with the intermittent terrestrial nocturnal development of ‘gravitational ischemia’ in the retina, wherein the decreased blood flow is accompanied metabolically by decreased oxygen tension, a critically important metric, with a detrimental influence on nerve-related tissue generally. However, the natural mechanisms for releasing and resolving gravitational ischemia, which likely involve glymphatics and cerebrospinal fluid shifts, as well as REM, may gradually fail in old age. Concurrently associated with old age in some individuals is the deposition of alpha-synuclein and/or tau in the retina, together with similar deposition in the brain, and it is also associated with the development of Parkinson’s disease and/or Alzheimer’s disease, possibly as a maladaptive attempt to release and resolve gravitational ischemia. This suggests that a key metabolic parameter of Parkinson’s disease and Alzheimer’s disease may be a lack of oxygen in some neural tissues. There is some evidence that oxygen therapy (hyperbaric oxygen) may be an effective supplemental treatment. Many of the cardinal features of spaceflight-associated neuro-ocular syndrome (SANS) may potentially be explained as features of gravity opposition physiology, which becomes unopposed by gravity during spaceflight. Gravity opposition physiology may, in fact, create significant challenges for humans involved in long-duration space travel (long-term microgravity). Possible solutions may include the use of artificial gravitational fields in space, such as centrifuges. Full article

Background/Objectives: Oxidative stress plays a significant role in the development and progression of age-related macular degeneration (AMD). Retinal pigment epithelium (RPE) cells are specialized multifunctional cells indispensable for the maintenance of vision. The dysfunction and death of RPE cells in the macula characterize the onset and development of AMD. Of the various toxic agents that impact the health of the RPE, particular focus has been given to various forms of lipoproteins and their cytotoxic derivatives normally present in the retina. Oxidized low-density lipoprotein (OxLDL), derived from LDL in a pro-oxidative environment, is found adjacent to RPE cells as part of drusen, extracellular deposits that are a hallmark feature of AMD. OxLDL is a potent inflammatory agent and it has been implicated in cardiovascular and neurodegenerative conditions. The cellular molecular mechanisms triggered by OxLDL are only partially understood. The focus of this study was to characterize changes in the proteome of RPE cells after exposure to OxLDL, with a focus on the characterization and quantification of ubiquitinated proteins. Methods: Identification and quantification were performed with a high-resolution LC-MS/MS-based proteomics workflow after immune-enrichment for ubiquitinated peptides. Results: In total, out of the more than 1000 RPE ubiquitinated peptides quantified, OxLDL treatment caused a significant increase in ubiquitinated peptides compared to LDL and untreated cells. Principal component analysis (PCA) of the differentially ubiquitinated proteins (265) reduced the data complexity in two main groups of variables (proteins). Conclusions: Gene ontology enrichment analysis of the grouped proteins with the highest loading contribution to principal component 1 (PC1) and principal component 2 (PC2) revealed significant ubiquitination changes upon OxLDL treatment in proteins of the ubiquitin–proteasome system (UPS) responsible for proteasome-mediated catabolic processes and in protein members of the cellular translation machinery. Full article

Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet’s folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management. Full article

The regenerative potential of the mammalian retina is limited, yet identifying signaling pathways that influence progenitor cell behavior remains an important step toward understanding the mechanisms of retinal development and plasticity. Epidermal Growth Factor Receptor (EGFR) signaling has been implicated in regulating proliferation and differentiation in the central nervous system, but its role in the postnatal retina is less defined. In this study, we employed an ex vivo explant model of the postnatal mouse retina to investigate the effects of sustained Epidermal Growth Factor (EGF) stimulation. Our results demonstrate that EGF extends the proliferative activity of progenitors that are normally quiescent after birth. However, the sustained EGFR activation (10 ng/mL, for 7 days) in the postnatal retina not only promotes EGFR+ progenitor proliferation but also maintains co-expression of Otx2 and Chx10, revealing a distinct progenitor population, suggesting that extended EGF signaling influences lineage allocation. These findings indicate that EGFR activation can modulate both the maintenance and differentiation potential of retinal progenitors in a context-dependent manner. While additional studies are needed to determine whether these progenitors develop into mature, functional neurons, our work provides a framework for future investigations into signaling pathways that may be leveraged to influence retinal development and plasticity. Full article

Retinal degeneration (RD) is an intractable ophthalmic disorder with no effective treatments, and its pathogenesis is complex, involving multiple genes. Endoplasmic reticulum (ER) stress and neuronal apoptosis are key factors that drive neurodegeneration in retinal degeneration. B cell receptor-associated protein 31 (BAP31) is a transmembrane protein predominantly found in the ER, which plays an important role in regulating ER stress and apoptosis. To date, no studies have directly confirmed the association between BAP31 and retinal degenerative diseases. However, considering that ER dysfunction is a key trigger for retinal photoreceptor cell damage and that BAP31 acts as a core regulator of ER function, we hypothesize that BAP31 may be involved in the development of retinal degeneration by regulating ER homeostasis. Our study aimed to investigate the pathogenic mechanisms of BAP31 in retinal disorders. A rod-specific conditional knockdown of BAP31 mouse model (Rho-iCre-BAP31^fl/fl(−/−)) was employed to explore the role of BAP31 in retinal pathogenesis. The Rho-iCre-BAP31^fl/fl(−/−) mice exhibited phenotypes similar to retinitis pigmentosa (RP), including decreased ERG responses, photoreceptor degeneration, and reduced visual function. Optical coherence tomography (OCT) results showed that the outer nuclear layer (ONL) of the retina in conditional knockdown mice exhibited progressive thinning after 9 months of age; histopathological examination results were consistent with those of OCT. These findings indicated that the rod photoreceptor cells in the conditional knockdown mice showed damage and irregular arrangement starting at 9 months of age, with more prominent changes by 12 months. RNA sequence analysis of 12-month-old mice indicated enrichment of the phototransduction pathway, with significant downregulation of key genes (rhodopsin, recoverin, Gnat1, Pde6a, and Pde6b) involved in retinal development and phototransduction, along with a marked increase in Gfap expression (indicating glial activation and retinal damage). Quantitative real-time PCR and Western blot analyses showed significant upregulation of unfolded protein response (UPR) marker proteins (BIP, CHOP, XBP1, ATF4, ATF6), demonstrating robust ER stress activation. The findings suggest that BAP31 deficiency induces retinal degeneration, and the activation of the ER stress may contribute to the pathogenic mechanisms underlying this process. Full article

Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood–retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (S_mix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a S_mix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94–56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen’s egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections. Full article

Transcription factors orthodenticle homeobox 2 gene (OTX2), paired box 6 gene (PAX6), and SRY-box transcription factor 2 gene (SOX2) are key regulators of ocular morphogenesis; however, their comparative embryonic localization across species—and the correspondence between transcript and protein distributions—remain incompletely defined. Chromogenic in situ hybridization (CISH) was employed to detect OTX2, PAX6, and SOX2 transcripts, while biotin–streptavidin immunohistochemistry (IHC) was used to assess Otx2, Pax6, and Sox2 protein expression. A semi-quantitative scoring system was applied to evaluate positive structures across ocular compartments. Transcripts were predominantly localized to the retina in both species, with occasional low-level expression in the optic nerve, sclera, and eyelid. Proteins displayed broader distributions: Otx2 was abundant in the retina and eyelid, while Pax6 and Sox2 were detected in multiple tissues, including cornea and extraocular muscles. OTX2, PAX6, and SOX2 show retina-predominant transcription and wider protein expression across ocular tissues. These findings highlight spatial differences between transcript and protein localization, supporting a complex regulatory framework underlying vertebrate eye development. Full article

Background/Objectives: Visual dysfunction emerges during the mild cognitive impairment stage of early Alzheimer’s disease (AD). While previous studies have primarily focused on retinal pathology, the early pathological progression across central nodes of the visual pathway remains inadequately characterized. This study examined regional pathological and structural alterations throughout the visual pathway at different disease stages in APP/PS1 transgenic mice aged 3, 6, and 9 months. Methods: Cognitive function was first assessed using novel object recognition and Y-maze tests to stage disease progression. Subsequently, Histological staining was employed to systematically analyze pathological features in the retina, lateral geniculate nucleus (LGN), and primary visual cortex (V1). Evaluated parameters encompassed β-amyloid (Aβ) deposition levels, microglial activation status, total neuronal counts, parvalbumin (PV)-positive neuron numbers, and tissue thickness measurements of the retina and V1. Results: At 6 months, mice exhibited an early symptomatic phenotype with selective spatial working memory deficits while long-term memory remained intact. Pathological analysis revealed concurrent Aβ deposition and microglial activation in V1, retina, and hippocampus by 6 months, whereas comparable LGN changes manifested only at 9 months, demonstrating regional heterogeneity in disease progression. V1 neuronal populations remained stable through 6 months but showed significant reduction by 9 months, though PV-positive neurons were selectively preserved. The LGN exhibited no neuronal loss even at 9 months. Gross structural thickness of both retina and V1 remained unchanged across all timepoints. Conclusions: These findings demonstrate that early visual system pathology in this AD model extends beyond the retina. The primary visual cortex exhibits early pathological changes (Aβ deposition and neuroinflammation) concurrent with hippocampal involvement, progressing to selective neuronal loss in later stages. The severity and selectivity of V1 pathology surpass those observed in other visual pathway nodes, including the LGN. Thus, V1 could represent not merely an affected region but a promising site for elucidating early cortical AD mechanisms and developing novel diagnostic biomarkers. Full article