Hao Wu

Ocular drug delivery faces tremendous challenges in clinical practice. The eyeball possesses sophisticated anatomical and physiological characteristics that uniquely influence the pharmacokinetics of delivered drugs. This complexity necessitates innovative solutions to ensure effective drug delivery. Conventional ocular drug administration routes (topical, intravitreal, and systemic) each pose unique limitations. With the advancements of biomaterials science and medical engineering technology, nanofiber hydrogels have garnered significant attention, primarily represented by self‐assembled peptide‐based hydrogels and cellulose nanofiber‐based hydrogels. They can be tailored to have precise physical and chemical properties, enabling controlled release of drugs and enhanced biocompatibility. Furthermore, their nanofibrous structure mimics the extracellular matrix, promoting cell adhesion and tissue regeneration. This review introduces advanced manufacturing techniques which are capable of precisely modifying the properties of nanofiber hydrogels to meet specific therapeutic needs. The distinctive advantages of nanofiber hydrogels are elaborated in detail, including their ability to enhance drug penetration, provide sustained release, and reduce systemic toxicity. We also delve into the therapeutic applications, potential limitations, and developmental perspectives of nanofiber hydrogels. Preclinical studies have validated their efficacy in treating ophthalmologic conditions such as age‐related macular degeneration, bacterial keratitis, ocular alkali burns, and non‐infectious uveitis. However, translating these laboratory findings into clinical applications remains limited, primarily due to significant challenges in human trials, including species‐specific responses, the complexity of human biology, and the safety of nanofiber hydrogels. Future refinements in fabrication techniques and rigorous safety assessments are necessary to revolutionize the clinical application of nanofiber hydrogels.

Background: Circadian clock coordinates the physiologic and behavioral activities with a 24‐hour solar rhythm to maintain the temporal homeostasis of the body. In the mammalian retina, the circadian system regulates the physiological function of this organ. The realm of ocular circadian rhythm has earned kinds of research interest as the circadian rhythms dysfunction will disrupt the retinal homeostasis. Bmal1 functions as a major transcriptional regulator of the circadian clock. Results: In the retina, Bmal1 mediates the processing of light information, sustains photoreceptor viability and governs neurotransmitter release. Moreover, Bmal1 gene is believed to be a pathologic cofactor of the diabetic retinopathy (DR), age‐related macular degeneration (AMD), premature aging and refractive myopia. To date, the precise mechanisms underlying the pathological effects mediated by Bmal1 remain incompletely elucidated. Conclusions: This review presents recent findings and evidence regarding the contributory role of Bmal1 in retinal degeneration and its deficits, while exploring its therapeutic potential. And th review provides a comprehensive analysis of the underlying mechanisms of the clock gene Bmal1 in other diseases, with the aim of offering insights into innovative therapeutic strategies for retinopathy.

Age-related retinopathy is one of the leading causes of visual impairment and irreversible blindness, characterized by progressive neuronal and myelin loss. The damages caused by oxidation contributes to the hallmarks of aging and represents fundamental components in pathological pathways that are thought to drive multiple age-related retinopathies. Quercetin (Que), a natural polyphenol abundant in vegetables, herbs, and fruits, has been extensively studied for its long-term antioxidative effects mediated through diverse mechanisms. Additionally, Que and its derivatives exhibit a broad spectrum of pharmacological characteristics in the cellular responses of age-related retinopathy induced by oxidative stress, including anti-inflammatory, anti-neovascularization, regulatory, and neuroprotective effects in autophagy and apoptosis processes. This review mainly focuses on the antioxidative mechanisms and curative effects of Que treatment for various age-related retinopathies, such as retinitis pigmentosa, diabetic retinopathy, age-related macular degeneration, and glaucoma. Furthermore, we discuss emerging technologies and methods involving Que and its derivatives in the therapeutic strategies for age-related retinopathies, highlighting their promise for clinical translation.

Iron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and the overproduction of ROS. The maintenance of iron homeostasis is contingent upon the activity of the transferrin receptor (TfR), ferritin (Ft), and ferroportin (FPn). In the retina, iron accumulation and lipid peroxidation can contribute to the development of age-related macular degeneration (AMD). This phenomenon can be explained by the occurrence of the Fenton reaction, in which the interaction between divalent iron and hydrogen peroxide leads to the generation of highly reactive hydroxyl radicals. The hydroxyl radicals exhibit a propensity to attack proteins, lipids, nucleic acids, and carbohydrates, thereby instigating oxidative damage and promoting lipid peroxidation. Ultimately, these processes culminate in cell death and retinal degeneration. In this context, a comprehensive understanding of the exact mechanisms underlying ferroptosis may hold significant importance for developing therapeutic interventions. This review summarizes recent findings on iron metabolism, cellular ferroptosis, and lipid metabolism in the aging retina. We also introduce developments in the therapeutic strategies using iron chelating agents. Further refinements of these knowledges would deepen our comprehension of the pathophysiology of AMD and advance the clinical management of degenerative retinopathy. A comprehensive search strategy was employed to identify relevant studies on the role of ferroptosis in AMD. We performed systematic searches of the PubMed and Web of Science electronic databases from inception to the current date. The keywords used in the search included “ferroptosis”, “AMD”, “age-related macular degeneration”, “iron metabolism”, “oxidative stress”, and “ferroptosis pathways”. Peer-reviewed articles, including original research, reviews, meta-analyses, and clinical studies, were included in this paper, with a focus on the molecular mechanisms of ferroptosis in AMDs. Studies not directly related to ferroptosis, iron metabolism, or oxidative stress in the context of AMD were excluded. Furthermore, articles that lacked sufficient data or were not peer-reviewed (e.g., conference abstracts, editorials, or opinion pieces) were not considered.

Hydrogels are distinguished by their exceptional ability to absorb and retain large volumes of water within their complex three‐dimensional polymer networks, which is advantageous for the development of intraocular lenses (IOLs). Their innate hydrophilicity offers an optimal substrate for the fabrication of IOLs that simulate the natural lens' accommodation, thereby reducing irritation and facilitating healing after surgery. The swelling and water retention characteristics of hydrogels contribute to their notable biocompatibility and versatile mechanical properties. However, the clinical application of hydrogels faces challenges, including managing potential adverse postimplantation effects. Rigorous research is essential to ascertain the safety and effectiveness of hydrogels. This review systematically examines the prospects and constraints of hydrogels as innovative materials for IOLs. Our comprehensive analysis examines their inherent properties, various classification strategies, cross‐linking processes, and sensitivity to external stimuli. Additionally, we thoroughly evaluate their interactions with ocular tissues, underscoring the potential for hydrogels to be refined into seamless and biologically integrated visual aids. We also discuss the anticipated technological progress and clinical uses of hydrogels in IOL manufacturing. With ongoing technological advancements, the promise of hydrogels is poised to evolve from concept to clinical reality, marking a significant leap forward in ophthalmology characterized by improved patient comfort, enhanced functionality, and reliable safety.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.