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Exosomes, extracellular vesicles and the eye.
Rudraprasad, D, Rawat, A, Joseph, J
Experimental eye research. 2022;:108892
Abstract
Exosomes are a subset of extracellular vesicles which accommodate a cargo of bioactive biomolecules that generally includes proteins, nucleic acids, lipids, sugars, and related conjugates depicting the cellular environment and are known to mediate a wide array of biological functions, like cellular communication, cellular differentiation, immunomodulation, neovascularization, and cellular waste management. The exponential implication of exosomes in the pathological development and progression of various disorders including neurodegenerative diseases, cardiovascular diseases, and cancer has offered a tremendous opportunity for exploring their role in ocular conditions. Ocular diseases such as age-related macular disease, glaucoma, infectious endophthalmitis, diabetic retinopathy, autoimmune uveitis etc face various challenges in their early diagnosis and treatments due to contributing factors such as delay in the onset of symptoms, microbial identification, difficulty in obtaining samples for biopsy or being diagnosed as masquerade syndromes. Studies have reported unique exosomal cargos that are involved in successful delivery of miRNA or proteins to recipient cells to express desired expression or exploited as a diagnostic marker for various diseases. Furthermore, engineered exosomes can be used for targeted delivery of therapeutics and exosomes being natural nanoparticles found in all types of cells, host may not elicit an immune response against it. With the rapid advancement of opting personalized therapeutics, extending exosomal research to sight-threatening ocular infections can possibly advance the current diagnostic and therapeutic approaches. This review briefs about the current knowledge of exosomes in visual systems, advancements in exosomal and ophthalmic research, participation of exosomes in the pathogenesis of common ocular diseases, the challenges for exosomal therapies along with the future of this promising domain of research for diseases that fatally threaten billions of people worldwide.
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Ocular Adverse Events After COVID-19 Vaccination.
Ng, XL, Betzler, BK, Testi, I, Ho, SL, Tien, M, Ngo, WK, Zierhut, M, Chee, SP, Gupta, V, Pavesio, CE, et al
Ocular immunology and inflammation. 2021;(6):1216-1224
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Abstract
PURPOSE The COVID-19 pandemic has galvanized the development of new vaccines at an unprecedented pace. Since the widespread implementation of vaccination campaigns, reports of ocular adverse effects after COVID-19 vaccinations have emerged. This review summarizes ocular adverse effects possibly associated with COVID-19 vaccination, and discusses their clinical characteristics and management. METHODS Narrative Literature Review. RESULTS Ocular adverse effects of COVID-19 vaccinations include facial nerve palsy, abducens nerve palsy, acute macular neuroretinopathy, central serous retinopathy, thrombosis, uveitis, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease reactivation, and new-onset Graves' Disease. Studies in current literature are primarily retrospective case series or isolated case reports - these are inherently weak in establishing association or causality. Nevertheless, the described presentations resemble the reported ocular manifestations of the COVID-19 disease itself. Hence, we hypothesize that the human body's immune response to COVID-19 vaccinations may be involved in the pathogenesis of the ocular adverse effects post-COVID-19 vaccination. CONCLUSION Ophthalmologists and generalists should be aware of the possible, albeit rare, ocular adverse effects after COVID-19 vaccination.
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Roles of Exosomes in Ocular Diseases.
Liu, J, Jiang, F, Jiang, Y, Wang, Y, Li, Z, Shi, X, Zhu, Y, Wang, H, Zhang, Z
International journal of nanomedicine. 2020;:10519-10538
Abstract
Exosomes, nanoscale vesicles with a diameter of 30 to 150 nm, are composed of a lipid bilayer, protein, and genetic material. Exosomes are secreted by virtually all types of cells in the human body. They have key functions in cell-to-cell communication, immune regulation, inflammatory response, and neovascularization. Mounting evidence indicates that exosomes play an important role in various diseases, such as cancer, cardiovascular diseases, and brain diseases; however, the role that exosomes play in eye diseases has not yet been rigorously studied. This review covers current exosome research as it relates to ocular diseases including diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, glaucoma, traumatic optic neuropathies, corneal diseases, retinopathy of prematurity, and uveal melanoma. In addition, we discuss recent advances in the biological functions of exosomes, focusing on the toxicity of exosomes and the use of exosomes as biomarkers and drug delivery vesicles. Finally, we summarize the primary considerations and challenges to be taken into account for the effective applications of exosomes.
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CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.
Dalvin, LA, Shields, CL, Orloff, M, Sato, T, Shields, JA
Retina (Philadelphia, Pa.). 2018;(6):1063-1078
Abstract
PURPOSE To review immune checkpoint inhibitor indications and ophthalmic side effects. METHODS A literature review was performed using a PubMed search for publications between 1990 and 2017. RESULTS Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. CONCLUSION Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.
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The role of eye-associated lymphoid tissue in corneal immune protection.
Knop, E, Knop, N
Journal of anatomy. 2005;(3):271-85
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Abstract
Because the cornea is optimized for refraction, it relies on supporting tissues for moistening and nutrition and in particular for immune protection. Its main support tissue is the conjunctiva, in addition to the lacrimal gland, the latter which provides soluble mediators via the tear film. The cornea and conjunctiva constitute a moist mucosal surface and there is increasing evidence that apart from innate defence mechanisms, also lymphoid cells contribute to the normal homeostasis of the corneal surface. A Medline-based literature search was performed in order to review the existing literature on the existence, composition and functions of mucosa-associated lymphoid tissue (MALT) at the ocular surface for corneal protection. The existence of lymphoid cells at the ocular surface and appendage has been known for many years, but for a long time they were believed erroneously to be inflammatory cells. More recent research has shown that in addition to the known presence of lymphoid cells in the lacrimal gland, they also form MALT in the conjunctiva as conjunctiva-associated lymphoid tissue (CALT) and in the lacrimal drainage system as lacrimal drainage-associated lymphoid tissue (LDALT). Together this constitutes an eye-associated lymphoid tissue (EALT), which is a new component of the mucosal immune system of the body. When the topographical distribution of CALT is projected onto the ocular surface, it overlies the cornea during eye closure and is hence in a suitable position to assist the corneal immune protection during blinking and overnight. It can detect corneal antigens and prime respective effector cells, or distribute protective factors as secretory IgA.