Intraocular exosomes in eye diseases

2021 ◽  
Vol 21 ◽  
Author(s):  
Hui Zhang ◽  
Xiaomin Zhang ◽  
Xiaorong Li
Keyword(s):  
Messenger Rna ◽  
Biological Fluids ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Pathological State ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Ecm Remodeling ◽  
Age Related ◽  
Eye Tissues

: Exosomes, nanosized extracellular vesicles with a size of 30–150nm, contain many biological materials, such as messenger RNA (mRNA), microRNA (miRNA), proteins, and transcription factors. It has been identified in all biological fluids and recognized as an important part of intercellular communication. While the role of exosomes in cancer has been studied in-depth, our understanding of their relevance for ocular tissues has just begun to evolve. Intraocular fluids, including aqueous humor and vitreous humor, play a role in nourishing eye tissues and in expelling metabolites. In the pathological state, intraocular exosomes can mediate pathological processes such as ECM remodeling, retinal inflammation, and blood-retinal barrier dysfunction. Herein, we reviewed the latest advances of intraocular exosomes in the research of several eye diseases, including glaucoma, age-related macular degeneration, myopia, and ocular tumors, and discuss how intraocular exosomes contribute to the pathogenesis and progression of multiple eye diseases.

scholarly journals C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function

2017 ◽  
Vol 312 (3) ◽  
pp. C244-C253 ◽  
Author(s):  
Blanca Molins ◽  
Anna Pascual ◽  
Méndez ◽  
Victor Llorenç ◽  
Javier Zarranz-Ventura ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Protein Isoforms ◽  
Age Related Macular Degeneration ◽  
C Reactive Protein ◽  
Barrier Dysfunction ◽  
Blood Retinal Barrier ◽  
Reactive Protein ◽  
Anti Vegf ◽  
Age Related

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

The Role of microRNAs in Osteoporosis Diagnostics

2021 ◽  
Vol 30 (03) ◽  
pp. 222-229
Author(s):  
Matthias Hackl ◽  
Elisabeth Semmelrock ◽  
Johannes Grillari
Keyword(s):  
Bone Mass ◽  
Bone Metabolism ◽  
Messenger Rna ◽  
Biological Fluids ◽  
Clinical Diagnostics ◽  
Bone Architecture ◽  
Estrogen Metabolism ◽  
Age Related

AbstractMicroRNAs (miRNAs) are short (18–24 nucleotides) non-coding RNA sequences that regulate gene expression via binding of messenger RNA. It is estimated that miRNAs co-regulate the expression of more than 70% of all human genes, many of which fulfil important roles in bone metabolism and muscle function. In-vitro and in-vivo experiments have shown that the targeted loss of miRNAs in distinct bone cell types (osteoblasts and osteoclasts) results in altered bone mass and bone architecture. These results emphasize the biological relevance of miRNAs for bone health.MiRNAs are not only considered as novel bone biomarkers because of their biological importance to bone metabolism, but also on the basis of other favorable properties: 1) Secretion of miRNAs from cells enables “minimally invasive” detection in biological fluids such as serum. 2) High stability of miRNAs in serum enables the retrospective analysis of frozen blood specimens. 3) Quantification of miRNAs in the serum is based on the RT-PCR - a robust method that is considered as the gold standard for the analysis of nucleic acids in clinical diagnostics.With regard to osteoporosis, it has been shown that many of the known risk factors are characterized by distinct miRNA profiles in the affected tissues: i) age-related loss of bone mass, ii) sarcopenia, iii) changes in estrogen metabolism and related changes Loss of bone mass, and iv) diabetes. Therefore, numerous studies in recent years have dealt with the characterization of miRNAs in the serum of osteoporosis patients and healthy controls, and were able to identify recurring miRNA patterns that are characteristic of osteoporosis. These novel biomarkers have great potential for the diagnosis and prognosis of osteoporosis and its clinical outcomes.The aim of this article is to give a summary of the current state of knowledge on the research and application of miRNA biomarkers in osteoporosis.

Application of 25-National Eye Institute Visual Function Questionnaire in ophthalmological patients

2020 ◽  
Vol 2 (3) ◽  
pp. 1-8
Author(s):  
Luciano Mesquite Simmo ◽  
Carissa Fouad Ibrahim ◽  
Senice Alvarenga Rodrigues Silva ◽  
Thai Nunes Andrade ◽  
Doora Faleiros Leite ◽  
...  
Keyword(s):  
Visual Function ◽  
Peripheral Vision ◽  
Statistical Significance ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Ischemic Optic Neuropathy ◽  
Age Related ◽  
Visual Function Questionnaire ◽  
The Impact

Objective: To compare the vision-targeted health related quality of life (HRQOL) between neuro-ophthalmological patients and other eye diseases by the National Eye Institute 25-Item Visual Function Questionnaire. Methods: Cross sectional study with a control group and patients with the following pathologies: primary open-angle glaucoma (POAG), diabetic retinopathy (DR), age-related macular degeneration (ARMD), non-arteritic ischemic optic neuropathy (NAION), intracranial hypertension (IH), optic neuritis (ON), ptosis and cataract. Results: All comparisons of the subscales scores among the control group and the patient groups were statistically significant (p<0.05) except for “ocular pain” (p=0.160), “social functioning” (p=0.052) and “peripheral vision” (p=0.112). The control group had the best scores across all dimensions of the NEI VFQ-25. Interestingly, the ARMD and cataract groups presented the best and worst total scores of NEI VFQ-25, respectively. The lowest subscales scores were found in the cataract, in the NAION/ON, and in the POAG groups. Finally, the comparison between the NAION/ON/IH patients and the other eye diseases did not show statistical significance in any subscale. Conclusion: The NEI VFQ-25 showed the impact of various eye conditions in vision-targeted HRQOL, and no difference was measured between neuro-ophthalmological patients and other eye diseases

scholarly journals Posterior segment eye diseases in Ijebu, Southwestern Nigeria

2018 ◽  
Vol 6 (1) ◽  
pp. 8
Author(s):  
Tayo Julius Bogunjoko ◽  
Adekunle O. Hassan ◽  
Adunola Ogunro ◽  
Toyin Akanbi ◽  
Bidemi Abudu
Keyword(s):  
Diabetic Retinopathy ◽  
Posterior Segment ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Systematic Sampling ◽  
Slit Lamp ◽  
Central Visual Field ◽  
Southwestern Nigeria ◽  
Ogun State ◽  
Age Related

Background: To review cases of posterior segment eye diseases (PSEDs) seen at the Eye Foundation Centre Ijebu, Nigeria in a 5 year period for planning purposes.Methods: Data was collected from patients’ case notes from January 2006 to December 2011. A systematic sampling of 468 patients from 1173 case notes of patient with (PSEDs) was done. Information retrieved was: age, sex, state of residence and diagnosis. All patients were examined by the glaucoma and the vitroretinal specialist as the case may be. They had visual acuity, refraction, slit lamp examination (including intraocular pressure (IOP) with Goldman applanation tonometer), and dilated fundoscopy with (bilateral indirect ophthalmoscopy) BIO, slit lamp using 20 D, 78 D and 90 D respectively. The glaucoma patients in addition had central visual field (CVF), Central cornea thickness (CCT), fundus photograph and in some cases optical coherence tomography (OCT) done in addition to the above.Results: The mean age was 59.98 years (SD 17.67) and the age range is 5-95 years. Males outnumbered females by 63% to 37%. The diseases were more common in age group 61 to 80. Patients’ attendances were mostly from Ijebu division of Ogun state (57%). Glaucoma is the commonest cause of attendance 262 (56%) followed by diabetic retinopathy 29 (6.2%) and age-related macular degeneration (ARMD) 28 (6.0%).Conclusions: Glaucoma, diabetic retinopathy and ARMD were noted as the commonest PSEDs in Ijebu division in Southwestern Nigeria.

scholarly journals Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10279
Author(s):  
Gabriella D. Hartman ◽  
Nathan A. Lambert-Cheatham ◽  
Mark R. Kelley ◽  
Timothy W. Corson
Keyword(s):  
Vision Loss ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Neuroprotective Effects ◽  
Multifunctional Protein ◽  
Age Related ◽  
Transcription Factor Activation ◽  
Molecule Inhibitor ◽  
Orally Bioavailable ◽  
Endothelial Growth Factor

Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are associated with aging and the number of those affected is expected to increase as the global median age and life expectancy continue to rise. With this increase in prevalence, the development of novel, orally bioavailable therapies for neovascular eye diseases that target multiple pathways is critical, since current anti-vascular endothelial growth factor (VEGF) treatments, delivered by intravitreal injection, are accompanied with tachyphylaxis, a high treatment burden and risk of complications. One potential target is apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1). The multifunctional protein APE1/Ref-1 may be targeted via inhibitors of its redox-regulating transcription factor activation activity to modulate angiogenesis, inflammation, oxidative stress response and cell cycle in neovascular eye disease; these inhibitors also have neuroprotective effects in other tissues. An APE1/Ref-1 small molecule inhibitor is already in clinical trials for cancer, PDR and diabetic macular edema. Efforts to develop further inhibitors are underway. APE1/Ref-1 is a novel candidate for therapeutically targeting neovascular eye diseases and alleviating the burden associated with anti-VEGF intravitreal injections.

scholarly journals Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress

2021 ◽  
Vol 14 (8) ◽  
pp. 1260-1273
Author(s):  
Zi-Yan Cai ◽  
◽  
Ke Liu ◽  
Xuan-Chu Duan ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vision Loss ◽  
Eye Diseases ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Classical Pathway ◽  
Age Related ◽  
Important Relationship

Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

An enhanced OCT image captioning system to assist ophthalmologists in detecting and classifying eye diseases

2020 ◽  
Vol 28 (5) ◽  
pp. 975-988
Author(s):  
Sivamurugan Vellakani ◽  
Indumathi Pushbam
Keyword(s):  
Short Term Memory ◽  
Clinical Decision ◽  
True Positive Rate ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Superior Performance ◽  
Image Captioning ◽  
Generative Adversarial Network ◽  
Adversarial Network ◽  
Age Related

Human eye is affected by the different eye diseases including choroidal neovascularization (CNV), diabetic macular edema (DME) and age-related macular degeneration (AMD). This work aims to design an artificial intelligence (AI) based clinical decision support system for eye disease detection and classification to assist the ophthalmologists more effectively detecting and classifying CNV, DME and drusen by using the Optical Coherence Tomography (OCT) images depicting different tissues. The methodology used for designing this system involves different deep learning convolutional neural network (CNN) models and long short-term memory networks (LSTM). The best image captioning model is selected after performance analysis by comparing nine different image captioning systems for assisting ophthalmologists to detect and classify eye diseases. The quantitative data analysis results obtained for the image captioning models designed using DenseNet201 with LSTM have superior performance in terms of overall accuracy of 0.969, positive predictive value of 0.972 and true-positive rate of 0.969using OCT images enhanced by the generative adversarial network (GAN). The corresponding performance values for the Xception with LSTM image captioning models are 0.969, 0.969 and 0.938, respectively. Thus, these two models yield superior performance and have potential to assist ophthalmologists in making optimal diagnostic decision.

scholarly journals Epidemiological factors associated with health knowledge of three common eye diseases: A community-based pilot survey in Hong Kong

2020 ◽  
Vol 8 ◽  
pp. 205031212094304
Author(s):  
Perseus WF Wong ◽  
Jordy KP Lau ◽  
Bonnie NK Choy ◽  
Kendrick C Shih ◽  
Alex LK Ng ◽  
...  
Keyword(s):  
Hong Kong ◽  
Macular Degeneration ◽  
Medical History ◽  
Health Knowledge ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Knowledge Level ◽  
Community Based ◽  
Pilot Survey ◽  
Age Related

Objectives: To assess the proportions of respondents in the general community having heard or awareness, and their knowledge level, of three common eye diseases: age-related macular degeneration, cataract, and glaucoma. We also attempted to assess for risk factors that may be associated with any variations, which will help identify the areas of inadequate knowledge and demographics of potential audiences for focused health education. Methods: We conducted a community-based pilot survey for the residents from a southern suburb of Hong Kong in early 2016, by inviting all aged 50 or above to complete a standardized questionnaire in the local community hall. Results: Most of the 222 respondents have heard, or awareness, of cataract (92.79% or 81.98%, respectively), followed by glaucoma (86.94% or 52.70%, respectively), and age-related macular degeneration (51.35% or 29.28%, respectively). The results of Cronbach’s alpha (α > 0.7) and Spearman’s correlation coefficient (p < 0.01) suggested that the internal consistency, convergent and discriminant validities of the questionnaire were acceptable for the study population. Compared to a previous Hong Kong survey in 2002, the proportions of having heard of the three eye diseases were greater, but the overall knowledge remained limited. From a maximum knowledge score of 29, the median scores for age-related macular degeneration, cataract, and glaucoma were 9, 13, and 14, respectively. Except for the treatment of cataract, the knowledge level in most areas was low. Sociodemographic factors and medical history, rather than behavioral factors, were more likely to be associated with having a higher knowledge level. Subjects with family or friends with a history of glaucoma or age-related macular degeneration were more aware and knowledgeable, but not for subjects who were current and past smokers or alcohol drinkers. For age-related macular degeneration, gender modified the effect between age and knowledge level, while age was a confounder of having medical history, and having heard or awareness, of the disease. Conclusion: Despite a larger proportion of the community having heard or awareness since 15 years ago, much effort remains for improving health knowledge of these three eye diseases in Hong Kong. We recommend targeting respondents with higher lifestyle risks, such as current and past smokers or alcohol drinkers, as a focused audience, and utilizing family members, relatives, or friends as another way of distributing health information.

scholarly journals Oxidative stress-mediated TXNIP loss causes RPE dysfunction

2019 ◽  
Vol 51 (10) ◽  
pp. 1-13 ◽  
Author(s):  
Min Ji Cho ◽  
Sung-Jin Yoon ◽  
Wooil Kim ◽  
Jongjin Park ◽  
Jangwook Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Common Factor ◽  
Age Related Macular Degeneration ◽  
Autophagic Flux ◽  
Blood Retinal Barrier ◽  
Rpe Cells ◽  
Age Related

Abstract The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.

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