Search Results (89)

The DMD gene is best known for its product dystrophin, a large rod-shaped protein that plays a critical role in muscular membrane strength and integrity. Mutations affecting dystrophin lead to Duchenne muscular dystrophy, a fatal X-linked disease characterized by muscular weakness and breakdown. In addition to the full-length dystrophin product that is most often associated with disease, the DMD gene also encodes multiple shorter isoforms of dystrophin with diverse functions. One isoform in particular, Dp71, has been increasingly found to play a wide variety of roles throughout the body. In this narrative review, we consolidate the numerous studies on Dp71 to provide a comprehensive foundation for future work. We outline and summarize the current state of knowledge on the role of Dp71 in the brain, the retina, and skeletal muscles, identifying current knowns and unknowns in the field. We also explore Dp71-based therapies currently being tested in the pre-clinical landscape and identify potential limitations for clinical translation. Full article

This review is intended to highlight the need for non-invasive and earlier therapies for diabetic retinal disease (DRD), one of the most common complications of diabetes, with a high and increasing socioeconomic burden. Due to the growing evidence regarding the key role of neurodegeneration in the earliest stages of the disease and the underlying pathophysiological mechanisms, the relevance of evaluating the potential efficacy of neuroprotective therapies is emphasized. More specifically, the review addresses the current state of a promising neuroprotective approach based on the inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) using specific inhibitors administered via eyedrops, which allow direct retinal action on the neurovascular unit. The review discusses the main preclinical findings of a therapeutic strategy based on one DPP-4 inhibitor, sitagliptin, against early DRD in different experimental animal models and in vitro studies. In summary, sitagliptin eyedrops exhibit neuroprotective, anti-inflammatory, and antioxidant properties while reducing glial activation, hyperpermeability of the blood–retinal barrier, and the formation of acellular capillaries, leading to a functional improvement of the diabetic retina. However, as sitagliptin efficacy has only been evaluated at the preclinical level, clinical studies are needed to validate the translational applicability and long-term efficacy of topical administration not only of sitagliptin but also of other DPP-4 inhibitors for treating retinal diseases in which neurodegeneration plays a pathogenic role. Full article

The scope of the present study is to conduct a comprehensive review of the anatomy, function, major pathological conditions and clinical significance of ocular lymphatic vessels. In recent years, it has become evident that ocular lymphatics play a major role in the pathogenesis and progression of ocular disorders. Therefore, we delved into this emerging field and described newly proposed mechanisms that may explain the involvement of ocular lymphatics in healthy and pathological states. Lymphatics are present in a plethora of ocular tissues primarily under pathological conditions, including limbal stroma, optic nerve, ocular muscles, lacrimal glands and sclera. The conjunctiva contains an extensive lymphatic network, whereas the cornea and retina are typically devoid of lymphatic vessels under physiological conditions. Inflammatory conditions can give birth to nascent lymphatic vessel sprouting. Growing evidence emphasizes the role of ocular lymphatics in glaucoma pathogenesis, suggesting a previously unknown aqueous humor drainage pathway mediated by lymphatic contribution. This review is based mainly on evidence from animal and experimental models, as human clinical data remain limited; therefore, caution is warranted when translating these findings into clinical practice. By gaining insight into the mechanisms and the clinical significance of eye lymphatics, this review aims to address novel insights for future research and treatment of eye diseases, as well as to highlight a misconception that has persisted for decades in ophthalmology. Full article

Background/Objectives: Arterial hypertension might lead to serious organ damage and complications like hypertensive retinopathy. The retina is the only place in the human body where microscopic blood vessels can be directly investigated. This enables early diagnosis of arterial hypertension-mediated organ damage. Untreated hypertensive retinopathy leads to vision loss in its advanced stages. There are many methods of assessing changes in the arterioles; however, the most accurate is adaptive optics (RTX1™ device with AODetectArtery software, ver. 3.0., Imagine Eyes, Orsay, France). It provides a resolution of 1.6 μm, which is superior to conventional imaging techniques. Optical coherence tomography angiography can serve as an early, minimally invasive marker of microvascular damage. Across the studies analyzed, the WLR (Wall-to-Lumen Ratio) exhibited significantly higher values when comparing individuals with hypertensive retinopathy to normotensives (0.31 vs. 0.26). The main aim of this review is to present the application of adaptive optics in the early diagnosis of hypertensive retinopathy. Methods: The search strategy included 267 original studies, among which 12 were selected to be described and analyzed in this review based on criteria including original research and studies performed on humans with hypertensive retinopathy. Results: RTX1™ enables the assessment of arterial parameters such as the Wall Thickness (WT), Lumen Diameter (LD), Outer Diameter (OD), Wall-to-Lumen Ratio (WLR) and Wall Cross Sectional Area (WCSA). These parameters differ depending on the arterial hypertension. The WLR was identified to be the parameter that differs in the vast majority of analyzed studies when comparing hypertensive patients to normotensive patients. Vascular parameters were also found to change depending on different organisms’ states, treatment applications and etiological causes of disease. Furthermore, changes in retinal arterial parameters were associated with increased cardiovascular risk in observational studies. RTX1™ was also identified to provide very good intra- and interobserver variability. Conclusions: RTX1™ is a valuable tool in the examination of arterial vessels and in establishing associations between retinal vascular parameters and a patient’s clinical state. Full article

The retina is a complex sensory neural tissue composed of six major types of neurons and one type of glial cell. The cell fate specification of retinal cells is tightly governed by intrinsic factors and extrinsic microenvironmental cues. Among the key regulators directing retinal cell fate differentiation is a group of bHLH family transcription factors (TFs). Our previous work demonstrated that the bHLH TF Ngn3 exhibits robust potential to induce retinogenesis in both distantly related fibroblasts in vitro and late retinal progenitor cells (RPCs) in vivo. However, the underlying molecular mechanisms remain largely elusive. In this study, we combined immunohistological examination and RNA-seq and ATAC-seq analyses to investigate the cellular and molecular mechanisms governing Ngn3-driven retinogenesis in late RPCs. Our results revealed that Ngn3 overexpression promotes premature cell cycle exit in late RPCs and remodels their transcriptomic and epigenomic landscape towards a state favoring rod photoreceptor and RGC differentiation. Furthermore, cross-comparison with Ngn3-overexpressing fibroblasts in vitro revealed cell-type-specific mechanisms underlying Ngn3-mediated neuronal fate reprogramming. These findings advance our understanding of Ngn family-mediated retinal cell fate regulation and provide a mechanistic framework for optimizing Ngn3-based retinal regeneration strategies for the treatment of retinal degeneration diseases. Full article

To perform screening of the retina on a population scale, an automated procedure is required that incorporates accurate, reproducible, interpretable, and computationally costeffective models. Existing approaches using convolutional or transformer architectures typically do not adequately represent both fine-grained pathology and large-scale retinal context simultaneously, which could adversely affect their reliability if used for large-scale applications in clinical practice. In this paper, we propose a hierarchical transformer-based screening framework for retinal fundus images that incorporates patch-based tokenization, global transformer encoding, and hierarchical aggregation of contextual information. We also developed a lightweight prediction head that supports screening for both single and multiple diseases. The framework has been evaluated using standard screening metrics, robustness, and cross-dataset generalization analyses on two eye retinopathy image databases: EyePACS and RFMiD. With regard to screening for a binary outcome of diabetic retinopathy, our method provided an accuracy of 89.4% and an area under the receiver operating characteristic (AUROC) curve of 93.6% on EyePACS and attained an accuracy of 95.2% and a macro-averaged F1 score of 82.7% on RFMiD. Our hierarchical transformer achieved improved robustness to degraded images and increased generalizability across datasets compared with all current state-of-the-art models. The proposed hierarchical transformer demonstrates strong potential for large-scale retinal screening and provides a promising foundation for future clinically validated deployment. Full article

Mitochondrial reactive oxygen species (mtROS) play a dual role in retinal physiology, acting as essential redox signalling mediators under homeostatic conditions but driving oxidative damage and neurodegeneration once regulatory thresholds are exceeded. Owing to the exceptionally high energetic demands of retinal neurons and supporting cells, even subtle perturbations in mitochondrial redox balance can precipitate progressive retinal dysfunction. Increasing evidence indicates that retinal neurodegenerative diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and inherited optic neuropathies, are characterised not by uniform oxidative stress, but by disease- and stage-specific mtROS signatures shaped by mitochondrial quality control capacity. This review synthesises current insights into the sources, regulation, and signalling functions of mtROS in the retina, with particular emphasis on threshold-dependent redox transitions, reverse electron transport, and the progressive failure of mitochondrial quality control mechanisms, including mitophagy, mitochondrial dynamics, and redox-responsive transcriptional networks. The limitations of non-selective antioxidant strategies are critically examined, highlighting why indiscriminate ROS suppression has yielded limited clinical benefit. In contrast, emerging therapeutic approaches aimed at recalibrating mitochondrial redox homeostasis, rather than abolishing physiological signalling, are discussed in the context of disease stage, metabolic state, and mitochondrial competence. By integrating redox biology with mitochondrial quality control and precision medicine concepts, this review proposes a unifying framework in which retinal neurodegeneration is governed by regulated mtROS signalling and the progressive exhaustion of mitochondrial resilience. This model defines critical therapeutic windows for mitochondria-targeted intervention and provides a framework for biomarker-guided patient stratification. Full article

Glaucoma is no longer viewed solely as a pressure-mediated optic neuropathy but as a chronic neurodegenerative disease with a strong immune component. Across experimental models and patient samples, convergent inflammatory circuitry complement activation, NLRP3 inflammasome signaling, and microglial reactivity emerge as a central driver of retinal ganglion cell (RGC) dysfunction and death. Local complement upregulation (C1q, C3, C5) in the retina and optic nerve head (ONH) promotes aberrant synaptic tagging, phagoptosis, and membrane attack complex stress. In parallel, biomechanical strain, ischemia, mitochondrial damage, and danger-associated molecular patterns prime and activate the NLRP3 inflammasome in microglia, astrocytes, and ONH cells, leading to caspase-1 activation, IL-1β/IL-18 maturation, and pyroptotic or apoptotic injury. Microglia integrate these cues, shifting from early protective surveillance to chronic maladaptive states that amplify complement and inflammasome outputs. This review synthesizes mechanistic links within the complement NLRP3 microglia axis, considers systemic and adaptive immune contributions, and proposes a translational framework for immune-based clinical stratification. The literature for this review was identified through searches of PubMed, Web of Science, and Scopus using combinations of the terms ‘glaucoma’, ‘complement’, ‘inflammasome’, ‘NLRP3’, ‘microglia’, and ‘neuroinflammation’. Priority was given to recent experimental, translational, and clinical studies. We then evaluate emerging immunomodulatory therapies, complement inhibitors, inflammasome blockers, microglial state reprogrammers, cytokine biologics, and cell-derived immunoregulatory approaches, highlighting biomarkers and trial design needs. An immune systems view of glaucoma enables precision neuroprotection for patients who progress despite controlled intraocular pressure. Full article

The translocator protein (TSPO), an evolutionarily conserved protein located on the outer mitochondrial membrane, is typically expressed at low levels in the central nervous system under normal physiological conditions. However, its expression can increase in response to various pathological conditions, such as neurodegenerative diseases and neuroinflammation. Retinitis pigmentosa (RP) refers to a group of inherited degenerative diseases of the retina; the progression of the pathology is linked to a chronic inflammatory state that leads to the progressive loss of photoreceptors and ultimately to blindness. One of the key processes contributing to the gradual loss of photoreceptors is neuroinflammation, a mechanism in which the TSPO plays a newly studied role. In this context, TSPO could be an excellent target. In the current study, rd10 mice of both sexes were treated with a TSPO ligand, PIGA1138, as an ophthalmic suspension (1 mg/mL) from post-natal day (P)18 to P30, P60, and P90. Retinal function was evaluated through electroretinography, while visual acuity was assessed using the Prusky Water Maze task. Additionally, molecular analyses were performed to assess TSPO expression, alongside examinations of retinal morphology. Results showed significant retinal preservation, reduced photoreceptor loss, and improved retinal responses, suggesting preserved visual function. These findings highlight PIGA1138’s potential in mitigating retinal degeneration and preserving function in retinal diseases like RP. Full article

Gene therapy offers a promising new frontier in the treatment of inherited and acquired retinal disease. This review describes the current surgical delivery approaches for gene therapy to the retina—subretinal, suprachoroidal, and intravitreal—and provides an update on the state of the art for each method in 2025. Full article

Background: Diabetic retinopathy (DR) is a leading cause of preventable vision impairment in individuals with diabetes. Early detection is essential, yet often hindered by subtle disease progression and reliance on manual expert screening. This study introduces an AI-based framework designed to achieve robust multiclass DR classification from retinal fundus images, addressing the challenges of early diagnosis and fine-grained lesion discrimination. Methods: The framework incorporates preprocessing steps such as pixel intensity normalization and geometric correction. A Hybrid Local-Global Retina Super-Resolution (HLG-RetinaSR) module is developed, combining deformable convolutional networks for local lesion enhancement with vision transformers for global contextual representation. Classification is performed using a hierarchical approach that integrates three models: a Convolutional Neural Network (CNN), DenseNet-121, and a custom multi-branch RefineNet-U architecture. Results: Experimental evaluation demonstrates that the combined HLG-RetinaSR and RefineNet-U approach consistently achieves precision, recall, F1-score, and accuracy values exceeding 99% across all DR severity levels. The system effectively emphasizes vascular abnormalities while suppressing background noise, surpassing existing state-of-the-art methods in accuracy and robustness. Conclusions: The proposed hybrid pipeline delivers a scalable, interpretable, and clinically relevant solution for DR screening. By improving diagnostic reliability and supporting early intervention, the system holds strong potential to assist ophthalmologists in reducing preventable vision loss. Full article

The clinical electroretinogram (ERG) is a non-invasive diagnostic test used to assess the functional state of the retina by recording changes in the bioelectric potential following brief flashes of light. The recorded ERG waveform offers ways for diagnosing both retinal dystrophies and neurological disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Parkinson’s disease. In this study, different time-series-based machine learning methods were used to classify ERG signals from ASD and typically developing individuals with the aim of interpreting the decisions made by the models to understand the classification process made by the models. Among the time-series classification (TSC) algorithms, the Random Convolutional Kernel Transform (ROCKET) algorithm showed the most accurate results with the fewest number of predictive errors. For the interpretation analysis of the model predictions, the SHapley Additive exPlanations (SHAP) algorithm was applied to each of the models’ predictions, with the ROCKET and KNeighborsTimeSeriesClassifier (TS-KNN) algorithms showing more suitability for ASD classification as they provided better-defined explanations by discarding the uninformative non-physiological part of the ERG waveform baseline signal and focused on the time regions incorporating the clinically significant a- and b-waves of the ERG. With the potential broadening scope of practice for visual electrophysiology within neurological disorders, TSC may support the identification of important regions in the ERG time series to support the classification of neurological disorders and potential retinal diseases. Full article

Drones have been widely used in precision agriculture to capture high-resolution images of crops, providing farmers with advanced insights into crop health, growth patterns, nutrient deficiencies, and pest infestations. Although several machine and deep learning models have been proposed for plant stress and disease detection, their performance regarding accuracy and computational time still requires improvement, particularly under limited data. Therefore, this paper aims to address these challenges by conducting a comparative analysis of three State-of-the-Art object detection deep learning models: YOLOv8, RetinaNet, and Faster R-CNN, and their variants to identify the model with the best performance. To evaluate the models, the research uses a real-world dataset from potato farms containing images of healthy and stressed plants, with stress resulting from biotic and abiotic factors. The models are evaluated under limited conditions with original data of size 360 images and expanded conditions with augmented data of size 1560 images. The results show that YOLOv8 variants outperform the other models by achieving larger mAP@50 values and lower inference times on both the original and augmented datasets. The YOLOv8 variants achieve mAP@50 ranging from 0.798 to 0.861 and inference times ranging from 11.8 ms to 134.3 ms, while RetinaNet variants achieve mAP@50 ranging from 0.587 to 0.628 and inference times ranging from 118.7 ms to 158.8 ms, and Faster R-CNN variants achieve mAP@50 ranging from 0.587 to 0.628 and inference times ranging from 265 ms to 288 ms. These findings highlight YOLOv8’s robustness, speed, and suitability for real-time aerial crop monitoring, particularly in data-constrained environments. Full article

The retina offers a unique window into both ocular and systemic health, motivating the development of AI-based tools for disease screening and risk assessment. In this study, we present a comprehensive evaluation of six state-of-the-art deep neural networks, including convolutional neural networks and vision transformer architectures, on the Brazilian Multilabel Ophthalmological Dataset (BRSET), comprising 16,266 fundus images annotated for multiple clinical and demographic labels. We explored seven classification tasks: Diabetes, Diabetic Retinopathy (2-class), Diabetic Retinopathy (3-class), Hypertension, Hypertensive Retinopathy, Drusen, and Sex classification. Models were evaluated using precision, recall, F1-score, accuracy, and AUC. Among all models, the Swin-L generally delivered the best performance across scenarios for Diabetes (AUC = 0.88, weighted F1-score = 0.86), Diabetic Retinopathy (2-class) (AUC = 0.98, weighted F1-score = 0.95), Diabetic Retinopathy (3-class) (macro AUC = 0.98, weighted F1-score = 0.95), Hypertension (AUC = 0.85, weighted F1-score = 0.79), Hypertensive Retinopathy (AUC = 0.81, weighted F1-score = 0.97), Drusen detection (AUC = 0.93, weighted F1-score = 0.90), and Sex classification (AUC = 0.87, weighted F1-score = 0.80). These results reflect excellent to outstanding diagnostic performance. We also employed gradient-based saliency maps to enhance explainability and visualize decision-relevant retinal features. Our findings underscore the potential of deep learning, particularly vision transformer models, to deliver accurate, interpretable, and clinically meaningful screening tools for retinal and systemic disease detection. Full article

People with C3 Dense Deposit Disease (C3DDD), a rare autoimmune disease, often also have ocular complications. Due to the rarity of this disease, there is little known about ocular complications in populations across the world. This paper aimed to assess literature on retinal complications in people with C3 Dense Deposit Disease. A scoping review was conducted and three databases (Embase, Medline All, and Web of Science) were searched using agreed search terms and Boolean operators. All references were imported into Covidence for screening by two reviewers. Any conflicts were resolved by a third reviewer. Data were extracted into an Excel spreadsheet and analysis was conducted using SPSS Version 29. After full text screening, 38 studies were included in the review. These studies were from 1990–2023 and most (67%) being case reports. All studies were conducted in the United States (55%) or Europe (45%). Most studies reported drusen-like deposits in the retina (75%) and retinal pigment epithelial detachment (18%) and macular atrophy (11%). Choroidal Neovascularisation (CNV) was found in 16% of cases. People with C3 Dense Deposit Disease are at risk of ocular complications, primarily drusen-like deposits. Further population-based research and progression is needed. Full article