Search Results (69)

Background/Objectives: Neural retina leucine zipper (NRL) is a transcription factor involved in the differentiation of rod photoreceptors. Pathogenic variants in the gene encoding NRL have been associated with autosomal dominant retinitis pigmentosa and autosomal recessive clumped pigmentary retinal degeneration. Only a dozen unrelated families affected by recessive NRL-related retinal dystrophy have been described. The purpose of this study was to expand the genotypic spectrum of this disease by reporting clinical and genetic findings of two unrelated families. Methods: Index patients affected by retinal dystrophy were genetically tested by whole-exome sequencing (WES) and whole-genome sequencing (WGS). Segregation analysis within the families was performed for candidate variants. A minigene assay was performed to functionally characterize a variant suspected to affect splicing. Results: Variant filtering revealed homozygous NRL variants in both families. The variant in patient A was a small deletion encompassing the donor splice site of exon 1 of transcript NM_006177.3. The minigene assay revealed that this variant led to two aberrant transcripts that used alternative cryptic donor splice sites located in intron 1. In patient B, a stop-gain variant was identified in the last exon of NRL in a homozygous state due to maternal uniparental disomy of chromosome 14. Conclusions: Our study expands the genotypic spectrum of autosomal recessive NRL-related retinal dystrophy. Moreover, it underscores the importance of actively maintaining bioinformatic pipelines for variant detection and the utility of minigene assays in functionally characterizing candidate splicing variants. Full article

Three-dimensional bioprinting (3DP) is transforming the field of regenerative medicine by enabling the precise fabrication of complex tissues, including the retina, a highly specialized and anatomically complex tissue. This review provides an overview of 3DP’s principles, its multi-step process, and various bioprinting techniques, such as extrusion-, droplet-, and laser-based methods. Within the scope of biomimicry and biomimetics, emphasis is placed on how 3DP potentially enables the recreation of the retina’s natural cellular environment, structural complexity, and biomechanical properties. Focusing on retinal tissue engineering, we discuss the unique challenges posed by the retina’s layered structure, vascularization needs, and the complex interplay between its numerous cell types. Emphasis is placed on recent advancements in bioink formulations, designed to emulate retinal characteristics and improve cell viability, printability, and mechanical stability. In-depth analyses of bioinks, scaffold materials, and emerging technologies, such as microfluidics and organ-on-a-chip, highlight the potential of bioprinted models to replicate retinal disease states, facilitating drug development and testing. While challenges remain in achieving clinical translation—particularly in immune compatibility and long-term integration—continued innovations in bioinks and scaffolding are paving the way toward functional retinal constructs. We conclude with insights into future research directions, aiming to refine 3DP for personalized therapies and transformative applications in vision restoration. Full article

Background: Bleeding within the orbit in the form of a subperiosteal or retrobulbar hematoma is a relatively common complication of trauma and surgery. It affects up to 30% of patients fractures involving the orbital bones. Most cases do not require surgical intervention because they do not cause retinal ischemia or optic nerve neuropathy. The above symptoms occur in only 0.5–1% of patients developing Orbital Compartment Syndrome (OCS). Due to the short period (60–100 min) of time in which the optic nerve and retina can tolerate increased intraocular pressure, it seemed reasonable to evaluate and standardize the surgical management protocol for this rare complication. Objective: The aim of this retrospective study was to retrospectively analyze cases of inframammary haematomas with clinically relevant correlations. Methods: Eighteen patients treated at the Department of Maxillofacial Surgery due to OCS, in Lodz and Poznan, Poland, between 2009 and 2022, were included. APTT, INR, systemic diseases, cause, location and size of hematoma, presence and number of fractures, visual disturbances and pupillary response on the day after surgery and one month after, the type of intervention and time between admission to the hospital and surgery were evaluated. Results: Statistically significant correlations were obtained between the size of the hematoma and the patients’ age, the degree of visual disturbance and the weakening of pupillary constriction, severe initial symptoms and poor postoperative outcomes at both postoperative periods studied, immediate and distant poor outcome after decompression surgery and good postoperative outcome persisting one month after. Conclusions: The results obtained in the study and the surgical protocol proposed by the authors are in line with the current state of knowledge regarding orbital hematomas. Some of the correlations described in the literature (such as OCS and anticoagulant treatment) were not demonstrated, but this is probably due to the small study group. Maintaining the 100 min limit as a standard was possible only in early postoperative diagnoses (only 1 of the patients was operated on up to 100 min after the appearance of symptoms). In other cases, the specialized diagnosis took an average of 2785 ± 4020 min or 46 ± 67 h. Full article

Background: Carotenoids are present throughout retina and body its dense deposition leads to an identifiable yellow spot in the macula. Macular pigment optical density (MPOD) measured in the macula is vital to macular well-being and high-resolution visual acuity. MPOD has also been associated with various health and disease states. We sought to review the literature on this topic and summarize MPODs role as a measurable modifiable clinical biomarker, particularly as a measure of the eye’s antioxidant capacity in the context of oxidative damage and retinal ischemia. Methods: A literature review collated the articles relevant to MPOD, carotenoid intake or supplementation, and their influence on various health and disease states. Results: Literature reveals that MPOD can serve as a reliable biomarker for assessing the retinal defense mechanisms against oxidative stress and the deleterious effects of excessive light exposure. Elevated MPOD levels offer robust protection against the onset and progression of age-related macular degeneration (AMD), a prevalent cause of vision impairment among the elderly population. MPOD’s implications in diverse ocular conditions, including diabetic retinopathy and glaucoma, have been explored, underscoring the real need for clinical measurement of MPOD. The integration of MPOD measurement into routine eye examinations presents an unparalleled opportunity for early disease detection, precise treatment planning, and longitudinal disease monitoring. Conclusions: Longitudinal investigations underscore the significance of MPOD in the context of age-related ocular diseases. These studies show promise and elucidate the dynamic nuances of MPOD’s status and importance as a measurable, modifiable clinical biomarker. Full article

This study investigates the protective effects of magnesium sulfate on dopamine neurons in the retinas of rats with 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease (PD). Rapidly progressing cognitive decline often precedes or coincides with the motor symptoms associated with PD. PD patients also frequently exhibit visual function abnormalities. However, the specific mechanisms underlying visual dysfunction in PD patients are not yet fully understood. Therefore, this study aims to investigate whether magnesium homeostasis affects dopaminergic neurons in the retina of PD rats. Thirty-six rats were divided into four groups: (1) control, (2) control with magnesium sulfate (control/MgSO₄), (3) Parkinson’s disease (PD), and (4) Parkinson’s disease with magnesium sulfate (PD/MgSO₄). The apomorphine-induced (APO) rotation test assessed the success of the PD models. The open-field experiment measured the rats’ anxiety levels. Tyrosine hydroxylase (TH) and glutamate levels, indicators of dopamine neuron survival, were detected using immunofluorescence staining. Protein levels of solute carrier family 41 A1 (SCL41A1), magnesium transporter 1 (MagT1), and cyclin M2 (CNNM2) in the retina were analyzed using Western blot. Results showed that, compared to the PD group, rats in the PD/MgSO₄ group had improved psychological states and motor performance at two and four weeks post-surgery. The PD/MgSO₄ group also exhibited significantly higher TH fluorescence intensity in the left retinas and lower glutamate fluorescence intensity than the PD group. Additional experiments indicated that the protein levels of SLC41A1, MagT1, and CNNM2 were generally higher in the retinas of the PD/MgSO₄ group, along with an increase in retinal magnesium ion content. This suggests that magnesium sulfate may reduce glutamate levels and protect dopamine neurons in the retina. Thus, magnesium sulfate might have therapeutic potential for visual functional impairments in PD patients. Full article

In this study, an advanced method for apricot tree disease detection is proposed that integrates deep learning technologies with various data augmentation strategies to significantly enhance the accuracy and efficiency of disease detection. A comprehensive framework based on the adaptive sampling latent variable network (ASLVN) and the spatial state attention mechanism was developed with the aim of enhancing the model’s capability to capture characteristics of apricot tree diseases while ensuring its applicability on edge devices through model lightweighting techniques. Experimental results demonstrated significant improvements in precision, recall, accuracy, and mean average precision (mAP). Specifically, precision was $0.92$, recall was $0.89$, accuracy was $0.90$, and mAP was $0.91$, surpassing traditional models such as YOLOv5, YOLOv8, RetinaNet, EfficientDet, and DEtection TRansformer (DETR). Furthermore, through ablation studies, the critical roles of ASLVN and the spatial state attention mechanism in enhancing detection performance were validated. These experiments not only showcased the contributions of each component for improving model performance but also highlighted the method’s capability to address the challenges of apricot tree disease detection in complex environments. Eight types of apricot tree diseases were detected, including Powdery Mildew and Brown Rot, representing a technological breakthrough. The findings provide robust technical support for disease management in actual agricultural production and offer broad application prospects. Full article

Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment. Full article

Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet—progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye. Full article

The human photoreceptor function is dependent on a highly specialised cilium. Perturbation of cilial function can often lead to death of the photoreceptor and loss of vision. Retinal ciliopathies are a genetically diverse range of inherited retinal disorders affecting aspects of the photoreceptor cilium. Despite advances in the understanding of retinal ciliopathies utilising animal disease models, they can often lack the ability to accurately mimic the observed patient phenotype, possibly due to structural and functional deviations from the human retina. Human-induced pluripotent stem cells (hiPSCs) can be utilised to generate an alternative disease model, the 3D retinal organoid, which contains all major retinal cell types including photoreceptors complete with cilial structures. These retinal organoids facilitate the study of disease mechanisms and potential therapies in a human-derived system. Three-dimensional retinal organoids are still a developing technology, and despite impressive progress, several limitations remain. This review will discuss the state of hiPSC-derived retinal organoid technology for accurately modelling prominent retinal ciliopathies related to genes, including RPGR, CEP290, MYO7A, and USH2A. Additionally, we will discuss the development of novel gene therapy approaches targeting retinal ciliopathies, including the delivery of large genes and gene-editing techniques. Full article

Oily fish is a rich source of energy, proteins, essential amino acids, lipids, vitamins, and minerals. Among the macronutrients with the highest contribution are lipids, mainly long-chain omega 3 polyunsaturated fatty acids (ω-3 LC-PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Both EPA and DHA play a beneficial role in promoting health and preventing many diseases, including cardiovascular diseases, such as stroke and acute myocardial infarction. They also contribute to the prevention of neurological, metabolic, and immune-system-related diseases, as well as supporting body-weight control. Oily fish consumption is also important at different stages of human life, from conception to old age. For example, DHA plays an important role in brain and retina development during fetal development and in the first two years of life, as it positively influences neurodevelopment, such as visual acuity, and cognitive functions. In contrast with the possible health benefits of the intake of oily fish, the presence of certain chemical pollutants, for example, heavy metals, can be a risk for the health of consumers, mainly in sensitive population groups such as pregnant women and children under 2 years of age. The presence of these pollutants is influenced to a greater extent by fish species, their role in the trophic chain, and their size. However, various studies state that the benefits outweigh the risk of consuming certain species. This review will be focused on the health benefits of the intake of three oily fish species, namely blue shark (Prionace glauca), shortfin mako shark (Isurus oxyrinchus), and swordfish (Xiphias gladius). Full article

Wet age-related macular degeneration (wAMD) is a chronic inflammation-associated neurodegenerative disease affecting the posterior part of the eye in the aging population. Aging results in the reduced functionality of cells and tissues, including the cells of the retina. Initiators of a chronic inflammatory and pathologic state in wAMD may be a result of the accumulation of inevitable metabolic injuries associated with the maintenance of tissue homeostasis from a young age to over 50. Apart from this, risk factors like smoking, genetic predisposition, and failure to repair the injuries that occur, alongside attempts to rescue the hypoxic outer retina may also contribute to the pathogenesis. Aging of the immune system (immunosenescence) and a compromised outer blood retinal barrier (BRB) result in the exposure of the privileged milieu of the retina to the systemic immune system, further increasing the severity of the disease. When immune-privileged sites like the retina are under pathological stress, certain age- and disease-related conditions may necessitate assistance from cells distant from the resident ones to help restore the functionality of the tissue. As a necessary part of tissue repair, inflammation is a major response to disease and recruits immune cells to the site of damage. We suspect that the specific reparative inflammatory responses are controlled by an autoantigen-T cell-mediated mechanism, a process that may be hindered in wAMD. Full article

Age-related macular degeneration (AMD) is a leading cause of blindness, and elucidating its underlying disease mechanisms is vital to the development of appropriate therapeutics. We identified differentially expressed genes (DEGs) and differentially spliced genes (DSGs) across the clinical stages of AMD in disease-affected tissue, the macular retina pigment epithelium (RPE)/choroid and the macular neural retina within the same eye. We utilized 27 deeply phenotyped donor eyes (recovered within a 6 h postmortem interval time) from Caucasian donors (60–94 years) using a standardized published protocol. Significant findings were then validated in an independent set of well-characterized donor eyes (n = 85). There was limited overlap between DEGs and DSGs, suggesting distinct mechanisms at play in AMD pathophysiology. A greater number of previously reported AMD loci overlapped with DSGs compared to DEGs between disease states, and no DEG overlap with previously reported loci was found in the macular retina between disease states. Additionally, we explored allele-specific expression (ASE) in coding regions of previously reported AMD risk loci, uncovering a significant imbalance in C3 rs2230199 and CFH rs1061170 in the macular RPE/choroid for normal eyes and intermediate AMD (iAMD), and for CFH rs1061147 in the macular RPE/choroid for normal eyes and iAMD, and separately neovascular AMD (NEO). Only significant DEGs/DSGs from the macular RPE/choroid were found to overlap between disease states. STAT1, validated between the iAMD vs. normal comparison, and AGTPBP1, BBS5, CERKL, FGFBP2, KIFC3, RORα, and ZNF292, validated between the NEO vs. normal comparison, revealed an intricate regulatory network with transcription factors and miRNAs identifying potential upstream and downstream regulators. Findings regarding the complement genes C3 and CFH suggest that coding variants at these loci may influence AMD development via an imbalance of gene expression in a tissue-specific manner. Our study provides crucial insights into the multifaceted genomic underpinnings of AMD (i.e., tissue-specific gene expression changes, potential splice variation, and allelic imbalance), which may open new avenues for AMD diagnostics and therapies specific to iAMD and NEO. Full article

Cellular senescence, a state of permanent cell cycle arrest in response to endogenous and exogenous stimuli, triggers a series of gradual alterations in structure, metabolism, and function, as well as inflammatory gene expression that nurtures a low-grade proinflammatory milieu in human tissue. A growing body of evidence indicates an accumulation of senescent neurons and blood vessels in response to stress and aging in the retina. Prolonged accumulation of senescent cells and long-term activation of stress signaling responses may lead to multiple chronic diseases, tissue dysfunction, and age-related pathologies by exposing neighboring cells to the heightened pathological senescence-associated secretory phenotype (SASP). However, the ultimate impacts of cellular senescence on the retinal vasculopathies and retinal vascular development remain ill-defined. In this review, we first summarize the molecular players and fundamental mechanisms driving cellular senescence, as well as the beneficial implications of senescent cells in driving vital physiological processes such as embryogenesis, wound healing, and tissue regeneration. Then, the dual implications of senescent cells on the growth, hemostasis, and remodeling of retinal blood vessels are described to document how senescent cells contribute to both retinal vascular development and the severity of proliferative retinopathies. Finally, we discuss the two main senotherapeutic strategies—senolytics and senomorphics—that are being considered to safely interfere with the detrimental effects of cellular senescence. Full article

Ultra-widefield fundus image (UFI) has become a crucial tool for ophthalmologists in diagnosing ocular diseases because of its ability to capture a wide field of the retina. Nevertheless, detecting and classifying multiple diseases within this imaging modality continues to pose a significant challenge for ophthalmologists. An automated disease classification system for UFI can support ophthalmologists in making faster and more precise diagnoses. However, existing works for UFI classification often focus on a single disease or assume each image only contains one disease when tackling multi-disease issues. Furthermore, the distinctive characteristics of each disease are typically not utilized to improve the performance of the classification systems. To address these limitations, we propose a novel approach that leverages disease-specific regions of interest for the multi-label classification of UFI. Our method uses three regions, including the optic disc area, the macula area, and the entire UFI, which serve as the most informative regions for diagnosing one or multiple ocular diseases. Experimental results on a dataset comprising 5930 UFIs with six common ocular diseases showcase that our proposed approach attains exceptional performance, with the area under the receiver operating characteristic curve scores for each class spanning from 95.07% to 99.14%. These results not only surpass existing state-of-the-art methods but also exhibit significant enhancements, with improvements of up to 5.29%. These results demonstrate the potential of our method to provide ophthalmologists with valuable information for early and accurate diagnosis of ocular diseases, ultimately leading to improved patient outcomes. Full article

Purpose: Gene therapy actually seems to have promising results in the treatment of Leber Congenital Amaurosis and some different inherited retinal diseases (IRDs); the primary goal of this strategy is to change gene defects with a wild-type gene without defects in a DNA sequence to achieve partial recovery of the photoreceptor function and, consequently, partially restore lost retinal functions. This approach led to the introduction of a new drug (voretigene neparvovec-rzyl) for replacement of the RPE65 gene in patients affected by Leber Congenital Amaurosis (LCA); however, the treatment results are inconstant and with variable long-lasting effects due to a lack of correctly evaluating the anatomical and functional conditions of residual photoreceptors. These variabilities may also be related to host immunoreactive reactions towards the Adenovirus-associated vector. A broad spectrum of retinal dystrophies frequently generates doubt as to whether the disease or the patient is a good candidate for a successful gene treatment, because, very often, different diseases share similar genetic characteristics, causing an inconstant genotype/phenotype correlation between clinical characteristics also within the same family. For example, mutations on the RPE65 gene cause Leber Congenital Amaurosis (LCA) but also some forms of Retinitis Pigmentosa (RP), Bardet Biedl Syndrome (BBS), Congenital Stationary Night Blindness (CSNB) and Usher syndrome (USH), with a very wide spectrum of clinical manifestations. These confusing elements are due to the different pathways in which the product protein (retinoid isomer-hydrolase) is involved and, consequently, the overlapping metabolism in retinal function. Considering this point and the cost of the drug (over USD one hundred thousand), it would be mandatory to follow guidelines or algorithms to assess the best-fitting disease and candidate patients to maximize the output. Unfortunately, at the moment, there are no suggestions regarding who to treat with gene therapy. Moreover, gene therapy might be helpful in other forms of inherited retinal dystrophies, with more frequent incidence of the disease and better functional conditions (actually, gene therapy is proposed only for patients with poor vision, considering possible side effects due to the treatment procedures), in which this approach leads to better function and, hopefully, visual restoration. But, in this view, who might be a disease candidate or patient to undergo gene therapy, in relationship to the onset of clinical trials for several different forms of IRD? Further, what is the gold standard for tests able to correctly select the patient? Our work aims to evaluate clinical considerations on instrumental morphofunctional tests to assess candidate subjects for treatment and correlate them with clinical and genetic defect analysis that, often, is not correspondent. We try to define which parameters are an essential and indispensable part of the clinical rationale to select patients with IRDs for gene therapy. This review will describe a series of models used to characterize retinal morphology and function from tests, such as optical coherence tomography (OCT) and electrophysiological evaluation (ERG), and its evaluation as a primary outcome in clinical trials. A secondary aim is to propose an ancillary clinical classification of IRDs and their accessibility based on gene therapy’s current state of the art. Material and Methods: OCT, ERG, and visual field examinations were performed in different forms of IRDs, classified based on clinical and retinal conditions; compared to the gene defect classification, we utilized a diagnostic algorithm for the clinical classification based on morphofunctional information of the retina of patients, which could significantly improve diagnostic accuracy and, consequently, help the ophthalmologist to make a correct diagnosis to achieve optimal clinical results. These considerations are very helpful in selecting IRD patients who might respond to gene therapy with possible therapeutic success and filter out those in which treatment has a lower chance or no chance of positive results due to bad retinal conditions, avoiding time-consuming patient management with unsatisfactory results. Full article