Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Hepatic zinc deficiency is a consistent feature of ALD, yet the therapeutic efficacy of zinc supplementation remains limited. This review examines the causal role of zinc deficiency in ALD pathogenesis and highlights low zinc bioavailability as a key determinant in disease progression. We discuss the regulatory roles of zinc transporters (ZIPs, ZnTs), metallothioneins, and redox-sensitive ligands in maintaining zinc homeostasis. Furthermore, we introduce zinc-glutathione (ZnGSH) as a novel zinc formulation that improves intestinal absorption and hepatic utilization of zinc. Unlike conventional zinc salts, ZnGSH overcomes multiple physiological barriers to zinc uptake in ALD, offering enhanced bioavailability in both gut and liver tissues. Thus, supplementation with bioavailable zinc may present a promising therapeutic strategy for ALD and, potentially, also other chronic liver diseases.

The interrelationship between type 2 diabetes mellitus (T2DM) and cancer reflects a convergence of molecular disturbances involving metabolism, inflammation, and cellular stress, often underpinned by genetic alterations. This review examines some key shared mechanisms of progression, with a focus on changes in plasma membrane dynamics, ion channel remodeling, Calcium (Ca) signaling, mitochondrial dysfunction, unfolded protein response, and oxidative stress. Changes in membrane composition, fluidity, lipid raft organization, and glycosylation affect receptor function and intracellular signaling in both diseases. These structural changes often occur in conjunction with the remodeling of ion channels. Ca influx, K, and Na are particularly affected, contributing to dysregulated excitability, proliferation, and immune modulation. Disturbed ion transport leads to intracellular Ca overload or oscillatory defects, impairing insulin secretion in diabetes and activating pro-oncogenic pathways in cancer. A sustained Ca imbalance further triggers the maladaptive activation of the UPR, while also affecting mitochondrial function. In T2DM, this response promotes β-cell dysfunction and insulin resistance, whereas in cancer, selective UPR engagement supports cell survival, angiogenesis, and immune evasion. Oxidative stress acts as both a trigger and amplifier in this cascade. Lipid peroxidation and mitochondrial dysfunction reinforce membrane instability and propagate damage, accelerating both metabolic decline and tumor progression. Therapeutically, interventions such as membrane lipid replacement and Ca channel blockers are being explored for their dual potential in addressing some of these molecular dysfunctions. By integrating molecular and epidemiological perspectives, this review highlights the potential of using precision therapies that target some of the overlapping properties of T2DM and cancer, offering a more unified strategy to confront these global health challenges.

The human genome contains a substantial legacy of ancient retroviral infections known as Human Endogenous Retroviruses (HERVs), composing 8 % of our DNA. In healthy young individuals, these elements are kept dormant by robust epigenetic mechanisms, primarily DNA methylation and repressive H3K9me3 histone marks. However, this epigenetic silencing deteriorates with age, leading to the reactivation of HERVs, particularly the youngest HERV-K subfamily. This report posits that this HERV awakening is not a passive byproduct of aging but an active, transmissible driver of pathology. The reactivation of HERVs leads to the production of retrovirus-like particles (RVLPs) that can induce senescence in healthy neighboring cells, propagating a contagious aging phenomenon. Furthermore, the accumulation of HERV-derived dsRNA and reverse-transcribed DNA triggers chronic innate immune responses through pathways including cGAS-STING and IFIH1-MAVS, fueling the systemic, low-grade inflammation characteristic of inflammaging, catalytically accelerated by exogenous viral infections. Pathogens such as SARS-CoV-2, Epstein-Barr Virus (EBV), and Herpes Simplex Virus (HSV-1) can directly transactivate HERVs via their own viral proteins, overwhelming the already compromised epigenetic controls in an aging host. This mechanistic link between viral triggers and endogenous retroviral activity is strongly implicated in a range of age-related diseases, including neurodegenerative disorders such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), where the HERV-K envelope protein is directly neurotoxic. It is also linked to autoimmune diseases like Multiple Sclerosis and various cancers. This report synthesizes these findings and identifies a novel mechanistic link between viral activity, chronic inflammation, and the onset of age-related diseases.

Selective pressures in the ocean promote the evolution of potent molecules that may be useful in therapeutic settings. Tunicates provide a rich source of bioactive molecules that have been shown to have anti-neoplastic and anti-microbial activities. Plitidepsin, a natural marine cyclic depsipeptide originally isolated from the tunicate Aplidium albicans, was originally developed as an anti-tumor drug, and has been approved for use in Australia in patients with advanced pretreated myeloma. Early in the SARS-CoV-2 pandemic, plitidepsin was shown to have potent preclinical efficacy against the virus, suggesting that it could be repurposed for the treatment of COVID-19. This review summarizes the clinical development of plitidepsin first as an anti-tumor drug, before providing a recapitulation of current efforts to repurpose the molecule as an antiviral therapy. The pharmacokinetic and pharmacodynamic data on plitidepsin will be analyzed, and the various experimental lines of evidence in support of the molecule's multifactorial mechanism of action will be explored. Finally, the available data on the use of plitidepsin in patients with COVID-19 will be presented, including results from a Phase I proof-of-concept study, real-world data from immunocompromised patients, and a look of results from a Phase III clinical trial that confirms the working hypothesis.

While the intricate and precisely specialized structure of the human eye is critical for its appropriate function, it also presents a number of anatomical and physiological barriers, such as tight junctions, enzymatic degradation, and dynamic fluid turnover, which highly restrict the intraocular bioavailability of various therapeutic compounds. This is more significant for those therapeutic compounds that are used for complications affecting the posterior segment. Accordingly, conventional therapeutic strategies for common ocular complications such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and infectious keratitis significantly demand invasive administration approaches and multiple injections, frequently resulting in various side effects and suboptimal therapeutic consequences. To address these major challenges, novel technologies, such as viral- and nanotechnology-based delivery systems, have provided emerging opportunities to bypass ocular barriers and facilitate targeted, maintained, and efficient drug and gene delivery. The present review aims to comprehensively describe the current advancements in both viral- and nanotechnology-based strategies for ocular diseases. It discusses the complex molecular structure and physiological functions of the ocular barriers, focusing on the exact mechanisms that restrict drug permeation. Moreover, this review describes the design principles, physicochemical properties, and therapeutic potential of diverse viral- and nanotechnology-based delivery systems. Their efficacy and safety profiles are thoroughly discussed across various pre-clinical and clinical studies. Furthermore, the review discusses the emergence of hybrid viral-nanotechnology delivery systems that combine the strengths of both approaches, offering enhanced targeting precision and biocompatibility. The major challenges linked to the clinical translation of these novel technologies, such as aspects of biocompatibility and immunogenicity are also addressed. This review highlights the significant transformative potential of viral vectors and nanotechnology in reforming ocular disease management and increasing patient quality of life.

Viral pathogens are one of the most significant causes of human carcinogenesis, contributing to up to 15-20 % of worldwide cancers. The gastrointestinal (GI) tract is one of the most vulnerable human organ system to virus-mediated tumorigenesis as a result of frequent exposure to viral infections and various immunological processes. The present review aims to describe the dual roles of viral infections in the development of gastrointestinal cancers (GICs), with a focus on Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). HIV represents an oncological challenge in the era of effective antiretroviral therapy (ART), where significant immune dysfunction, persistent inflammation, and gut microbiome disruption render infected patients more susceptible to various GICs. On the other hand, SARS-CoV-2 is an emerging viral pathogen whose potential role in oncogenesis remains controversial yet biologically plausible. In this context, SARS-CoV-2 tropism to the gastrointestinal tissues and its capacity to drive cytokine storms, profound dysbiosis, and immune exhaustion raise significant questions regarding its potential to act as a pro-tumorigenic factor. Discussing mechanistic insights from well-known oncogenic viral pathogens, the present review describes the direct and indirect mechanisms by which these two major viruses may affect GI tumorigenesis. Moreover, this review translates these mechanisms into clinical perspectives, underscoring implications for diagnostics, prevention, and therapeutic strategies, while highlighting urgent research priorities for long-term surveillance and biomarker discovery. It highlights the importance of continuous scientific awareness to address the increasing cancer risks presented by emerging and re-emerging viruses through bridging virology and oncology.

Inherited retinal dystrophies (IRDs) are a heterogeneous group of rare genetic disorders that affect multiple retinal cell types, including photoreceptors, Müller glia, bipolar cells, retinal ganglion cells (RGCs), and the retinal pigment epithelium (RPE). Recombinant adeno-associated viruses (rAAVs) have emerged as the leading vectors for gene delivery in the retina due to their safety profile and ability to drive long-term expression. However, achieving precise cell targeting and appropriate transgene regulation remains a key challenge. Recent advances in capsid engineering and the discovery of cell-type-specific regulatory elements have opened new avenues for improving the precision of rAAV-mediated therapies. These refined tools can be integrated with various therapeutic strategies, such as gene augmentation, genome editing, RNA modulation, and optogenetics, to expand the range and effectiveness of treatments for IRDs. This review focuses on recent developments in the customization of rAAV vectors to achieve cell-specific gene therapy for IRDs.

BONE: and bone-marrow associated cancers, including osteosarcoma, Ewing sarcoma, multiple myeloma, and various leukemias, are highly aggressive tumors with limited therapeutic options and poor outcomes. Viruses play a paradoxical role in these diseases, acting both as pathogenic drivers and as potential therapeutic agents. On one hand, oncogenic viruses such as Epstein-Barr virus (EBV), human T-cell leukemia virus type 1 (HTLV-1), and hepatitis viruses have been implicated in the initiation and progression of certain hematologic and skeletal malignancies. On the other hand, oncolytic viruses have emerged as promising 'friends,' engineered to selectively infect, lyse, and stimulate immune responses against malignant cells within the unique microenvironment of bone and bone marrow. This duality raises critical questions about how viral biology intersects with cancer pathogenesis and therapy. In this review, we explore the evidence for viral pathogens as both foes that contribute to tumorigenesis and friends that can be harnessed as novel therapeutic platforms. We further highlight delivery challenges, safety considerations, and translational opportunities that may shape the future of virotherapy for bone and marrow cancers.

Viral Infectious Ocular Diseases (VIODs) remain a major global cause of vision loss, ranging from highly transmissible conjunctivitis to blinding keratitis and complex neuro-ophthalmic syndromes. Furthermore, the Coronavirus Disease 2019 (COVID-19) pandemic and subsequent reported ocular diseases have fundamentally changed the landscape of VIOD epidemiology and management. Epidemiological data indicate heterogeneous effects on common infections such as Adenoviral conjunctivitis due to varying compliance with hygiene measures. Concurrently, systemic immunological events, notably those induced by COVID-19 infection or certain vaccinations, have been linked to the reactivation of latent Alphaherpesviruses, including Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV). The metagenomic next-generation sequencing (mNGS) offers a significantly improved diagnostic yield (up to 92.7 % in some cohorts) for complex infectious keratitis compared to conventional methods, providing an unbiased tool crucial for timely, targeted treatment. Therapeutic challenges are defined by the persistent threat of antiviral resistance, primarily driven by mutations in the viral Thymidine Kinase (TK) gene. To overcome poor ocular bioavailability, novel drug delivery systems (NDDS), such as Acyclovir-loaded Niosomes and Cubosomes, show promise by enabling sustained drug release and enhanced corneal permeation. Effective future VIOD control requires a multi-pronged strategy integrating robust global surveillance, rapid deployment of advanced molecular diagnostics, and the clinical implementation of resistance-beating therapies delivered via optimized nanocarrier platforms. This review provides the current understanding of VIODs, focusing on the epidemiological shifts observed post-2020, advancements in molecular diagnostics, challenges posed by antiviral resistance, and the emergence of next-generation therapeutic strategies.

Macrophages are key innate immune cells that defend against pathogens, maintain tissue homeostasis, and regulate inflammation. A complex network of post-translational modifications (PTMs) controls the flexibility and adaptability of macrophage functions. These modifications change the structure, function, location, and interactions of proteins through covalent mechanisms such as phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation. This enables macrophages to respond quickly and accurately to changes in their microenvironment. Dysregulated macrophage function is pivotal to the pathophysiology of inflammatory bowel disease (IBD) and the resultant outcomes following viral infections. Recent evidence suggests that macrophage PTMs provide a mechanistic link between IBD and viral infection. Viral infections may accelerate disease onset or exacerbate IBD activity. Viruses exploit the PTM machinery of host cells for their replication and immune evasion. This review discusses how PTM changes in macrophages caused by viral infections can lead to a long-lasting, pro-inflammatory state that could tip the balance of intestinal immunity toward chronic IBD. We elucidate the functions of traditional PTMs such as phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation, in conjunction with emerging modifications such as lactylation and citrullination (deimination). We emphasize their distinct roles in both antiviral responses and IBD pathogenesis, while also exploring therapeutic strategies targeting PTM pathways.

The Zika virus (ZIKV), a mosquito-borne Flavivirus, has emerged as a global health threat due to its severe neuroteratogenic effects, particularly during pregnancy. This mechanistic-to-translational synthesis examines how ZIKV disrupts fetal brain development and links molecular events to clinical manifestations of Congenital Zika Syndrome (CZS). Our review advances prior summaries by presenting a unifying neural progenitor cell (NPC)-centric pathway framework that integrates viral entry, host signaling disruption, cell fate outcomes, and imaging correlates. Once transmitted vertically, the virus targets NPCs, impairing proliferation, triggering apoptosis, and halting the cell cycle. It modulates host pathways such as PI3K-Akt-mTOR and p53 to enhance autophagy, avoid immune detection, and sustain replication. ZIKV also interferes with RNA interference and synaptic formation, contributing to cortical thinning, ventriculomegaly, and agenesis of the corpus callosum. Inflammatory responses further exacerbate tissue damage as ZIKV activates TLRs and inflammasomes, increasing proinflammatory cytokines and pyroptosis. Brain organoid and imaging studies highlight the virus's NPC tropism and capacity for lasting neurodevelopmental impairment-even in normocephalic infants. Importantly, ZIKV exhibits SOX2-dependent permissiveness with integrin αvβ5 functioning as a key dependency/attachment factor in neural and glioblastoma stem cells, distinguishing transcriptional state from receptor function. This intersection of neurotropism and potential oncolytic activity underscores the dual pathogenic and therapeutic implications of ZIKV. Literature was synthesized according to a predefined search strategy, with evidence appraised for quality, strengths, and limitations. This review highlights mechanistic pathways linking viral replication, immune modulation, and disrupted neurodevelopment, emphasizing implications for surveillance, therapeutic targets, and maternal-fetal health preparedness.

Neutrophil extracellular traps (NETs) are a network of fibrous structures composed of DNA, histones, and antimicrobial proteins released by neutrophils, which play a crucial role in the innate immune system's defense against infection. When neutrophils encounter pathogens, they can release NETs to capture and neutralize these invaders, preventing their spread and prompting other immune cells to destroy them. The classical inflammasome is a cytoplasmic polyprotein complex activated by infectious and/or non-infectious stimuli that activates the protease caspase-1 to induce pyroptosis and promotes the maturation and release of interleukin (IL)-1β and IL-18, while the non-classical inflammasome activates cysteinyl aspartate specific proteinase (caspase)-4/11 to induce pyroptosis. Inflammasome activation is also an important component of the innate immune response. This review elaborates on the constituent proteins and molecular regulation of NETs and inflammasomes, summarizes the crosstalk between NETs and inflammasomes and its negative effects in the disease process, and also discusses the therapeutic effects of drugs targeting NETs and/or inflammasomes on related diseases.

Inherited retinal diseases (IRDs) are a genetically and clinically heterogeneous group of disorders that cause progressive vision loss and often lead to blindness. The complexity of these conditions arises from pathogenic variants in over 330 different genes, making the development of effective treatments highly challenging. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach for IRDs, offering precise regulation of transcript expression and composition. Unlike traditional gene augmentation therapies, ASOs provide a flexible and sequence-specific strategy by modulating splicing patterns, blocking translation, or promoting RNA degradation. Advancements in ASO chemistry, including backbone and sugar modifications, have significantly improved their uptake, stability, specificity, and therapeutic efficacy, facilitating their application in a variety of diseases. This review provides a comprehensive analysis of ASO-based strategies for IRDs, touching upon their mechanisms of action, chemical modifications, delivery strategies, and current clinical advancements. Additionally, we discuss the challenges that remain, such as off-target effects, delivery barriers, and long-term safety concerns, while highlighting future innovations that may enhance the efficacy and safety of ASOs and broaden their clinical applicability. As ASO-based therapies continue to progress through preclinical and clinical development, they hold significant potential to reshape the therapeutic landscape for IRDs, offering personalized and targeted treatments for patients with these devastating conditions.

Diabetes and cancer are among the most prevalent chronic diseases globally, drawing increasing attention due to their shared features of metabolic and signaling dysregulation. Epidemiological evidence indicates that type 2 diabetes significantly elevates the risk of developing multiple types of tumors. This review highlights the key molecular intersections between diabetic pathophysiology and oncogenic processes, with a focus on how hyperinsulinemia and hyperglycemia contribute to tumor initiation and progression. These effects are primarily mediated through profound metabolic reprogramming, including hyperactivation of the hexosamine biosynthetic pathway (HBP) and the accumulation of advanced glycation end-products (AGEs), which promote sustained oxidative stress and chronic inflammation. Consequently, the tumor microenvironment (TME) undergoes substantial remodeling. The metabolism and function of immune cells are disrupted, promoting immune evasion. Meanwhile, cancer cells adapt by engaging mechanisms such as diabetes-induced epigenetic reprogramming, activation of the unfolded protein response (UPR), and alterations in the gut microbiota, thereby enhancing their survival advantage. Emerging evidence suggests that anti-diabetic agents targeting these metabolic intersections exhibit dual roles in cancer therapy, offering both therapeutic potential and potential risks. To address these complexities, future efforts should conduct multi-omics technologies to dissect the metabolic heterogeneity of diabetes-associated tumors, paving the way for precise and personalized therapeutic strategies for patients with this comorbidity.

The development of type 2 diabetes may be influenced by enterotypes and bacterial metabolites. The most important of these are short-chain fatty acids (SCFAs), which play a role in forming the gut-brain axis and in the process of lipogenesis. An increase in lipogenesis can lead to obesity. High levels of adipose tissue in the body trigger chronic inflammation and insulin resistance. This review examines how microbiota composition influences the pathogenesis of type 2 diabetes and the possibility of regulating microbiota through proper nutrition, fecal microbiota transplantation, and prebiotics and probiotics. Additionally, the review notes that an imbalance in the gut microbiota can contribute to diabetes progression and increase cancer risk through inflammatory and immune mechanisms.

Flaviviruses are emerging arthropod-borne viruses that cause severe endemic infections and epidemics on a global scale. Recent Zika virus outbreaks have highlighted a significant link between the virus and ocular abnormalities, increasing interest in the pathogenesis of Flaviviruses. Flavivirus pathogenesis involves a complex interplay between viral replication and immune responses, leading to a wide spectrum of human diseases. Flavivirus infections can cause ocular complications that are usually self-limiting but can result in irreversible visual impairment and vision loss. These complications can affect both the anterior and posterior segments of the eye, and symptoms can range from mild conjunctivitis to more severe conditions like uveitis and even the inflammation of the optic nerve. Ocular inflammation often arises from the immune system's response to viral infections. In ocular Flavivirus infections, the immune response aims to protect the eye, but it can sometimes lead to inflammation and tissue damage. In this review, we summarize the current knowledge of the major Flaviviruses (Zika, Dengue, Yellow Fever, and West Nile) reported to cause ocular manifestations in humans, with emphasis on viral immunopathogenesis. Hence, we discuss how Flaviviruses modulate immune responses and cause ocular manifestations.

Caspase family proteases, as aspartate-specific cysteine proteases, have long been considered to function exclusively in programmed cell death. However, emerging evidence indicates that their functions extends well beyond apoptosis. Members of this family exhibit numerous non-cell death functions through dynamic regulation of activity gradients and spatiotemporal localization, participating extensively in physiological processes such as neuronal synaptic remodeling, immune homeostasis regulation, and metabolic reprogramming, thereby forming a functional continuum from the molecular to the system level. Based on these novel functions, we propose a function-oriented classification of caspases into three categories: homeostatic, defensive, and remodeling types, while revealing their cross-category functional overlap. In addition, the development of conformation-specific inhibitors and microenvironment-responsive delivery systems provides precise regulatory tools for targeted therapy. This paper systematically summarizes the non-apoptotic functions of the caspase family and proposes a "spatiotemporal activity" dynamic model, opening new avenues for tumor therapy, neurodegenerative disease intervention, and immune disorder regulation.

Historically, patients with pancreatic cancer presented with hyperglycemia and glycemic intolerance, leading to a hypothesis that diabetes may be associated with pancreatic ductal adenocarcinoma (PDAC). Nearly 50 years later, our understanding about the association and pathophysiological link between diabetes and PDAC continues to expand. What has been elucidated is that new-onset diabetes, especially in patients with weight loss or over the age of 50, may be an early clinical sign of PDAC. Additionally, long-standing diabetes remains an independent risk factor for development of PDAC. The pathophysiology of both new-onset and long-standing diabetes and PDAC is closely linked to non-alcoholic steatopancreatitis, the local inflammatory microenvironment, and metabolic alterations that bidirectionally arise from and worsen diabetes. This review summarizes current evidence evaluating the association between diabetes and pancreatic cancer. We also review the pathophysiology of this interaction, and discuss how understanding these mechanism may allow prevention, diagnosis, and treatment of pancreatic malignancy.

The COVID-19 pandemic, caused by SARS-CoV-2, has had far-reaching consequences beyond acute respiratory illness, with growing evidence suggesting potential long-term oncogenic effects. Lung cancer, a leading cause of cancer-related mortality, may intersect with COVID-19 through shared molecular pathways and altered disease dynamics. SARS-CoV-2 can exacerbate outcomes in existing cancer patients and potentially contribute to de novo lung carcinogenesis or accelerate progression via chronic inflammation, oxidative stress, immune dysregulation, cellular senescence, cell cycle disruption, metabolic reprogramming, and autophagy impairment. It has been proven that although the SARS virus is not capable of integrating into the host genome, it uses the mechanisms of other human oncoviruses to cause lung cancer. Post-COVID-19 pulmonary fibrosis, observed in up to one-third of severe cases, may act as a tumor precursor bridge through sustained tissue remodeling, extracellular matrix stiffness, and hypoxia-induced epithelial-mesenchymal transition. Epidemiological studies indicate increased cancer-related mortality, metastatic reactivation of dormant cancer cells, and diagnostic delays, shifting presentations toward advanced stages during the pandemic. Synergistic risk factors, including smoking, air pollution, occupational exposures, and genetic predispositions, may further amplify oncogenic potential. The convergence of viral, environmental, and host factors creates a critical need for vigilant surveillance, biomarker development, and preventive strategies. This study aims to synthesize current epidemiological evidence, elucidate the molecular and cellular mechanisms by which SARS-CoV-2 may influence lung carcinogenesis, and highlight clinical implications to guide future research, screening, and therapeutic interventions.

Emerging and re-emerging viral infections represent a significant and escalating global health concern, frequently associated with a spectrum of systemic complications. Among these, ocular manifestations are increasingly recognized, contributing substantially to visual morbidity. The present review aims to provide an overview of the ocular sequelae of major emerging and re-emerging viral pathogens, highlighting their suggested and established roles in ocular neovascularization (ONV). It discusses the virological and immunological mechanisms, including direct viral cytopathic effects, virally-induced inflammation, dysregulation of angiogenic and anti-angiogenic factors (e.g., Vascular Endothelial Growth Factor), and activation of hypoxia-inducible pathways, which can contribute to neovascular processes in various ocular compartments such as the cornea, iris, retina, and choroid. The major viral agents addressed in this review are Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), West Nile virus (WNV), Dengue Virus (DENV), and other viruses with known or suspected ONV association. This study reviewed and summarized the literature regarding case reports and experimental models describing the association of these viral agents with ONV. Furthermore, it addresses diagnostic considerations and therapeutic strategies. Understanding the intricate interplay between these viral infections and ocular neovascular pathways is crucial for developing targeted therapeutic strategies to prevent vision loss in affected populations.