Current Eye Research最新文献

Purpose: Dry eye disease (DED), a multifactorial disease of the lacrimal system, manifests itself in patients with various symptoms such as itching, inflammation, discomfort and visual impairment. In its most severe forms, it results in the breakdown of the vital tissues of lacrimal functional unit and carries the risk of vision loss. Despite the frequency of occurrence of the disease, there are no effective curative treatment options available to date. Treatment using stem cells and its secreted factors could be a promising approach in the regeneration of damaged tissues of ocular surface. The treatment using secreted factors as well as extracellular vesicles has been demonstrated beneficial effects in various ocular surface diseases. This review provides insights on the usage of stem cell derived exosomes as a promising therapy against LG dysfunction induced ADDE for ocular surface repair.

Methods: In order to gain an overview of the existing research in this field, literature search was carried out using the PubMed, Medline, Scopus and Web of Science databases. This review is based on 164 publications until June 2024 and the literature search was carried out using the key words "exosomes", "lacrimal gland regeneration", "exosomes in lacrimal dysfunction".

Results: The literature and studies till date suggest that exosomes and other secreted factors from stem cells have demonstrated beneficial effects on damaged ocular tissues in various ocular surface diseases. Exosomal cargo plays a crucial role in regenerating tissues by promoting homeostasis in the lacrimal system, which is often compromised in severe cases of dry eye disease. Exosome therapy shows promise as a regenerative therapy, potentially addressing the lack of effective curative treatments available for patients with dry eye disease.

Conclusion: Stem cell-derived exosomes represent a promising, innovative approach as a new treatment option for ADDE. By targeting lacrimal gland dysfunction and enhancing ocular surface repair, exosome therapy offers potential for significant advances in dry eye disease management. Future research is needed to refine the application of this therapy, optimize delivery methods, and fully understand its long-term efficacy in restoring ocular health.

Purpose: To assess the therapeutic potential of extracellular vesicles (EVs) derived from stem cells and ocular tissues as a cell-free alternative to traditional stem cell therapies for a broad spectrum of ocular diseases.

Methods: A comprehensive literature review was performed, focusing on preclinical studies involving EVs derived from mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), neural progenitor cells, immune cells, and ocular-resident cells. Data were extracted on EV cellular origin, isolation methods, routes of administration, preclinical disease models, therapeutic outcomes, and proposed mechanisms of action. Registered clinical trials were also evaluated.

Results: EVs exhibited regenerative and immunomodulatory effects across a range of ocular conditions, including dry eye, uveitis, glaucoma, retinal degenerations, and optic neuropathies. Various cell sources have been explored for EV production, including MSCs, iPSCs, hESCs, retinal organoids, and other ocular tissue-resident cells. In addition, bioengineered EVs have been developed to modify surface properties or enhance therapeutic cargo. Reported mechanisms of action include miRNA-mediated gene regulation, immune modulation, and oxidative stress reduction. Several early-phase clinical trials are currently underway to translate these findings into human therapies.

Conclusion: Stem cell-derived EVs represent a promising next-generation, cell-free regenerative therapy for ocular diseases. While preclinical data are promising, successful clinical translation will require optimal EV source selection, scalable and GMP-compliant production, identification of disease-relevant mechanisms of action, rigorous cargo characterization, and alignment with regulatory standards.

Purpose: A stable ocular surface is crucial for maintaining ocular health by protecting against various infections. This is achieved by coordinated function of ocular structures (cornea, limbus, conjunctiva), innervation, and the tear film which forms a protective barrier over the ocular surface ensuring proper hydration, lubrication, and overall ocular comfort. This complex three-layered tear film secreted by different sources ensures its stability by adhesion to the corneal epithelium. Ocular surface fluid kinetics and tear secretion involve complex processes influenced by neural regulation, environmental factors, and molecular composition. Recent advances in cell biology and secretome has unravelled the mysteries of cellular cargo of almost every cell and system i.e. the extracellular vesicles (EVs) which facilitate intercellular communication. EVs are of different sizes, amongst which small EVs (sEVs) potentially are more informative than other EVs.

Methods: An extensive review of literature on sEVs in tears and ocular surface was conducted.

Results: Emerging literature on sEVs derived from ocular surface structures such as cornea and limbal stem cells contribute to corneal wound healing, regeneration and reduced fibrosis by the activation of specific proteins. A recent study documents that homeostasis between cornea and conjunctiva is maintained by the expression of specific genes triggering trans differentiation in diseased conditions. There is also mounting evidence on role of tear-derived sEVs in normal and diseased states. The approach in which tear layers secreted from three different sources form into a single tri-layered stable biofilm covering the entire ocular surface remains elusive. Hence not surprisingly, the tear sEVs therefore have been referred to as one entity and not attributed to any of the 3 different sources that they originate from.

Conclusion: This review attempts to present the recent concepts of sEVs, ocular surface, tears and highlight the gaps in our understanding of tear-derived exosomes and its potential role in homeostasis and disease conditions.

Purpose: Exosomes, small extracellular vesicles ranging from 30 to 150 nm in diameter, have emerged as crucial mediators of intercellular communication in ocular tissues. This review explores the roles of exosomes in ocular health and disease, focusing on their biogenesis, functions in different eye structures, and potential as diagnostic biomarkers and therapeutic agents.

Methods: This comprehensive review synthesizes current research on ocular exosomes, drawing from global studies to present an integrated view of exosome biology in the eye.

Results: Exosomes play vital roles in maintaining retinal homeostasis, corneal function, and lens transparency. They are implicated in the pathogenesis of major eye diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy. Recent advances have revealed the potential of exosomes as biomarkers for early disease detection and as vehicles for targeted drug delivery. Emerging technologies, such as microfluidics and nanotechnology, enhance exosome isolation and analysis capabilities.

Conclusions: Exosome research in ophthalmology is rapidly advancing, offering promising avenues for novel diagnostic and therapeutic approaches. However, challenges remain in standardization, scalability, and clinical translation. Addressing these issues and ethical considerations will be crucial for realizing the full potential of exosomes in improving ocular health outcomes globally.

Purpose: The cornea is a transparent avascular tissue that serves as the first line of defense against opportunistic pathogens and provides a smooth refractive surface for vision. Due to its external location, the cornea is vulnerable to stress from the outer environment. This can lead to corneal epithelial breakdown and subsequent corneal disease. Extracellular vesicles (EVs) are nano-sized vesicles enclosed within a lipid bilayer that are secreted by all cells in the body and play a key role in cell-to-cell communication. Within the cornea field, EVs and exosomes, the latter of which represents a subpopulation of small EVs, have emerged as potential therapies for treating corneal diseases and have increased our understanding of the mechanisms by which EVs, and more specifically, exosomes released by stressed or unhealthy cells, leads to corneal dysfunction and disease.

Methods: We conducted a literature search using PubMed and Google Scholar using keywords relevant to exosomes, extracellular vesicles, and cornea. We reviewed the literature focusing on EV studies on corneal wound healing and therapy.

Results: This review provides a comprehensive overview of the current state of exosome biology as it relates to corneal disease and wound healing. Studies to date provide compelling data indicating that EVs and exosomes may play an integral role in the maintenance of corneal homeostasis. EVs and exosomes also have exciting potential as therapeutics in corneal wound healing and disease; and their presence in tear fluid may serve as potential diagnostic biomarkers for ocular and systemic diseases.

Conclusion: While corneal exosome biology is still in its infancy state, continued progress in this area will improve our understanding of the functional capacity of these small vesicles in the human cornea and may lead to the development of novel regenerative therapies.

Exosomes are small membrane-bound vesicles which have emerged as crucial mediators in various biological and pathological processes, as well as potential therapeutic delivers. In recent years, the role of exosomes in the lens, a specialized tissue essential for vision, has been stressed. The purpose of this review is to sum up the current understanding of exosome function within the lens and their implications in lens-related diseases.

Purpose: This minireview discusses desmosome and hemidesmosome disassembly and/or internalization and subsequent release via exosomes in retinal pigmented epithelium (RPE) under oxidative stress conditions, and whether it may be a precursor to epithelial-mesenchymal transition in early Age-related Macular Degeneration (AMD).

Methods: Literature review and discussion of novel findings relevant to the focus of the review.

Results: The RPE forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in AMD, due to its essential role in visual homeostasis. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released via a dedicated machinery by all cells and carry out a multitude of functions related to cellular signaling and waste management. In the RPE they are released from both the apical and basal sides, and the cargo composition reflects this polarization. We have recently showed that exosomes released from the basolateral side of RPE cells under chronic oxidative stress conditions, contain desmosome and hemidesmosome proteins. Here we discuss the composition of desmosomes and hemidesmosomes in the RPE, the role of exosomes and ubiquitination pathways in their disassembly, and whether this dismantling is a precursor to epithelial-mesenchymal transition. Further considerations include how the exosome-mediated shedding of desmosome and hemidesmosome components is related to lysosomal and/or proteasomal overload, and how these pathways can be modulated to intervene in early stages of AMD.

Conclusions: This review provides an overview of the current knowledge about desmosome and hemidesmosome disassembly in RPE, its intersection with the exosome pathway, and potential role in epithelial-mesenchymal transition. We discuss several potential targets for therapeutic intervention in pre-symptomatic or early-stage AMD in these pathways.

A growing body of research on extracellular vesicles (EVs) in cancer has revealed their novel and crucial activities in the progression of tumors while also paving the way for potential therapeutic interventions. It is now known that EVs are natural delivery vehicles for particular payloads of source cells, enabling them to influence diverse functions of cells both in healthy and malignant cells. In this review, we comprehensively summarize mechanistic insights into sEV roles in RB, the most frequent intraocular malignancy that affects the retina of young children. We also explore the therapeutic potential of sEVs as an emerging area as biomarkers and vehicles for targeted therapy. Additionally, we address the potential challenges and limitations of translating sEVs-based technologies into clinical practice.

Purpose: Glaucoma is one of the leading causes of irreversible blindness, characterized by progressive visual field loss. Several risk factors are associated with developing the disease. However, the exact mechanisms or pathological pathways involved are still unknown. There is an urgent need to find the mechanisms and biomarkers for early detection and therapy to halt progression or cure the disease. Extracellular vesicles (EVs), specifically exosomes, have emerged as a crucial player in all aspects of glaucoma, including pathogenesis to therapeutic application with their cell-cell communication properties.

Methods: We performed a literature search on PubMed, Google Scholar, and Web of Science using different keywords. Next, we reviewed the literature with studies focusing on the role of EVs as a causative factor in disease progression, biomarker discovery based on their contents, and protection from glaucoma.

Results: Studies summarized here provide reports of differential EV miRNA and protein expression alterations when communicating with aqueous humor drainage tissues. We described how EV contents are involved in various pathways, including extracellular matrix remodeling and miRNA-mediated oxidative stress transmission between outflow tissues, thereby contributing to glaucoma. Extracellular vesicles, mainly derived from mesenchymal stem cells protecting the optic nerve from degeneration, have also been discussed as potential therapies for glaucoma.

Conclusions: Overall, this review provides a comprehensive discussion of the role of extracellular vesicles in glaucoma. We identified the challenges in finding major signaling molecules of glaucoma etiology. Lastly, we highlighted future directions to improve the treatment of glaucoma by extracellular vesicles.