Charles Ong, Mark Yu Zheng Wong, Kai Xiong Cheong et al. · Diagnostics · 2023
Traditionally, abnormalities of the retinal vasculature and perfusion in retinal vascular disorders, such as diabetic retinopathy and retinal vascular occlusions, have been visualized with dye-based fluorescein angiography (FA). Optical coherence tomography angiography (OCTA) is a newer, alternative modality for imaging the retinal vasculature, which has some advantages over FA, such as its dye-free, non-invasive nature, and depth resolution. The depth resolution of OCTA allows for characterization of the retinal microvasculature in distinct anatomic layers, and commercial OCTA platforms also provide automated quantitative vascular and perfusion metrics. Quantitative and qualitative OCTA analysis in various retinal vascular disorders has facilitated the detection of pre-clinical vascular changes, greater understanding of known clinical signs, and the development of imaging biomarkers to prognosticate and guide treatment. With further technological improvements, such as a greater field of view and better image quality processing algorithms, it is likely that OCTA will play an integral role in the study and management of retinal vascular disorders. Artificial intelligence methods-in particular, deep learning-show promise in refining the insights to be gained from the use of OCTA in retinal vascular disorders. This review aims to summarize the current literature on this imaging modality in relation to common retinal vascular disorders.
Cited by 29Open access
W. Zbiba, Issam Elleuch, Sana Sayadi et al. · BMC Ophthalmology · 2020
Congenital retinal macrovessels and retinal cavernous hemangioma are benign lesions. Their association is rare. Abnormal vascular development is likely to be responsible for their association. Swept source OCT and OCT angiography may be of a great contribution to better evaluate these retinal vascular disorders.
Cited by 10Open access
Deniz Dalkara, Olivier Goureau, Katia Marazova et al. · Human Gene Therapy · 2016
Retinal degenerative diseases are a leading cause of irreversible blindness. Retinal cell death is the main cause of vision loss in genetic disorders such as retinitis pigmentosa, Stargardt disease, and Leber congenital amaurosis, as well as in complex age-related diseases such as age-related macular degeneration. For these blinding conditions, gene and cell therapy approaches offer therapeutic intervention at various disease stages. The present review outlines advances in therapies for retinal degenerative disease, focusing on the progress and challenges in the development and clinical translation of gene and cell therapies. A significant body of preclinical evidence and initial clinical results pave the way for further development of these cutting edge treatments for patients with retinal degenerative disorders.
Cited by 123
Reza Raeisossadati, M Ferrari, Alexandre Hiroaki Kihara et al. · Epigenetics & Chromatin · 2021
In the developing vertebrate retina, retinal progenitor cells (RPCs) proliferate and give rise to terminally differentiated neurons with exquisite spatio-temporal precision. Lineage commitment, fate determination and terminal differentiation are controlled by intricate crosstalk between the genome and epigenome. Indeed, epigenetic regulation plays pivotal roles in numerous cell fate specification and differentiation events in the retina. Moreover, aberrant chromatin structure can contribute to developmental disorders and retinal pathologies. In this review, we highlight recent advances in our understanding of epigenetic regulation in the retina. We also provide insight into several aspects of epigenetic-related regulation that should be investigated in future studies of retinal development and disease. Importantly, focusing on these mechanisms could contribute to the development of novel treatment strategies targeting a variety of retinal disorders.
Cited by 40Open access
Yaqin Zhao, Bin Sun, Xuefei Fu et al. · Biomedicine & Pharmacotherapy · 2024
The distinctive role of Yes-associated protein (YAP) in the nervous system has attracted widespread attention. This comprehensive review strategically uses the retina as a vantage point, embarking on an extensive exploration of YAP's multifaceted impact from the retina to the brain in development and pathology. Initially, we explore the crucial roles of YAP in embryonic and cerebral development. Our focus then shifts to retinal development, examining in detail YAP's regulatory influence on the development of retinal pigment epithelium (RPE) and retinal progenitor cells (RPCs), and its significant effects on the hierarchical structure and functionality of the retina. We also investigate the essential contributions of YAP in maintaining retinal homeostasis, highlighting its precise regulation of retinal cell proliferation and survival. In terms of retinal-related diseases, we explore the epigenetic connections and pathophysiological regulation of YAP in diabetic retinopathy (DR), glaucoma, and proliferative vitreoretinopathy (PVR). Lastly, we broaden our exploration from the retina to the brain, emphasizing the research paradigm of "retina: a window to the brain." Special focus is given to the emerging studies on YAP in brain disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), underlining its potential therapeutic value in neurodegenerative disorders and neuroinflammation.
Cited by 12Open access
Chang-Jun Zhang, Zi‐Bing Jin · Current Medicine · 2023
Abstract Retinal homeostasis is maintained through a network of the nervous, circulatory, endocrine and immune systems. The integrity of the blood-retinal barrier, immune-inflammatory responses, and metabolic changes all significantly affect the maintenance of normal visual function. Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and other disorders, are a group of heterogeneous and multi-etiological diseases resulting in an irreversible visual impairment. Whether these disorders are inherited, acquired, or from systemic origins, the gradual loss of the retinal pigment epithelium (RPE) and/or retinal neurons is a common feat. This process often begins with compromised retinal integrity, followed by a disruption in the equilibrium of inflammation, immune response, metabolism, and other aspects, resulting in retinal dyshomeostasis that affects not only disease progression but also the effect of therapeutic intervention. Therefore, a comprehensive understanding of the retinal homeostasis and dyshomeostasis will assist the development of treatment strategies for retinal degenerative diseases and open new avenues for clinical translation.
Cited by 14Open access
Feliciana Menna, Laura De Luca, Alessandro Meduri et al. · Frontiers in Genetics · 2026
The retina is a highly specialized neural tissue characterized by extreme cellular differentiation, high metabolic demand, and lifelong exposure to environmental stressors. These features render retinal cell identity exquisitely dependent on epigenetic regulation of gene expression. Rare hereditary retinal disorders offer a unique framework for understanding how epigenetic mechanisms modulate genotype-phenotype relationships in the human eye. This Mini Review provides an integrated overview of DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA-mediated regulation in retinal development, homeostasis, and degeneration. We discuss how epigenetic dysregulation contributes to photoreceptor loss, phenotypic variability, and disease progression in inherited retinal dystrophies and syndromic disorders affecting the retina, and we highlight emerging translational opportunities and current limitations of epigenetic-based therapeutic strategies for rare retinal disease.
Cited by 0Open access
Hiromitsu Kunimi, Deokho Lee, Mari Ibuki et al. · The FASEB Journal · 2021
Retinal ischemia is a leading cause of irreversible blindness worldwide. Inner retinal dysfunction including loss of retinal ganglion cells is encountered in a number of retinal ischemic disorders. We previously reported administration of two different hypoxia-inducible factor (HIF) inhibitors exerted neuroprotective effects in a murine model of retinal ischemia/reperfusion (I/R) which mimics these disorders, as inner retinal degeneration could be involved in pathological HIF induction. However, this notion needs further investigation. Therefore, in this study, we attempted to use retina-specific Hif-1α conditional knockout (cKO) mice to uncover this notion more clearly under the same condition. Hif-1α cKO mice showed inner retinal neurodegeneration to a lesser extent than control mice. Hif-1α depletion in a murine 661W retinal cell line reduced cell death under pseudohypoxic and hypoxic conditions. Among hypoxia-related genes, the expression of BCL2 19 kDa protein-interacting protein 3 (Bnip3) was substantially upregulated in the inner retinal layer after retinal I/R. In this regard, we further examined Bnip3 depletion in retinal neurons in vitro and in vivo and found the similar neuroprotective effects. Our results support the notion that the HIF-1α/BNIP3 pathway may have a critical role in inner retinal neurodegeneration, which can be linked with the development of new promising therapeutics for inner retinal ischemic disorders.
Cited by 41
Reiva Farah Dwiyana, Ivan Daniel Banjarnahor, Inne Arline Diana et al. · Clinical Cosmetic and Investigational Dermatology · 2022
Incontinentia pigmenti (IP) is a rare genodermatosis, inherited in an X-linked dominant pattern, making it generally found among women. Among several characteristics of IP are four phases of skin manifestation that tend to follow Blaschko's lines, in addition to abnormalities of the eye, central nervous system (CNS), and teeth. Ocular involvement in IP patients can occur since birth, which can be classified into retinal or non-retinal disorders. Retinal disorders can result in detachment, which is a major ocular threat for IP patients. This article reports two IP cases with overlapped phases of skin disorders in baby girls with ocular manifestations since early life. Clinical signs and additional examination of the skin and eyes are utilized to make the diagnosis. All the features of the histopathological examination supported the diagnosis of IP, and ocular exams revealed abnormalities in the form of retinal neovascularization (RN). Although RN may resolve spontaneously, patients should be monitored for the development of other eye disorders such as visual impairment.
Cited by 1Open access
Shaojun Wang (743003), Yi Sun (118759), Jie Na (221422) et al. · Figshare · 2025
Human embryonic stem cells (hESC)-derived retinal organoids are sophisticated in vitro systems for dissecting the complex dynamics of human retinal development. The formation of the human retina is a precisely organized process that depends on the regulated differentiation of retinal progenitor cells; however, many of the basic mechanisms remain to be explored. Here, using hESC-derived retinal organoids, we elucidated the temporal contribution of RAX2 to retinal development, with an emphasis on photoreceptor cells (PC) formation. The results were corroborated using human fetal retinal tissue at various gestational ages. Using CRISPR/Cas9-mediated gene knockout, we delineated the essential role of RAX2 in modulating PC specifications. RAX2 deficiency significantly altered the expression of PAX6 and SOX2, two essential regulators of retinogenesis. Our results suggested that RAX2 is significant in retinal development, underpinning its potential as a therapeutic target in related retinal disorders.
Cited by 0Open access
Lars‐Olof Hattenbach, I. Scharrer, Marc Lüchtenberg et al. · Klinische Monatsblätter für Augenheilkunde · 2009
Our results indicate that thrombophilic disorders are associated with the development of retinal vein occlusion. Selective screening of young patients, patients with a personal or family history of thromboembolism, and patients without cardiovascular risk factors may be helpful in identifying retinal vein occlusion patients with thrombophilic defects.
Cited by 10
O'Leary, Fionn Timothy · Trinity's Access to Research Output (TARA) (Trinity College Dublin) · 2023
Cited by 0
Haohuan Xie, Wen Zhang, Mei Zhang et al. · Science Advances · 2020
Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide potential opportunities for studying human retinal development and disorders; however, to what extent ROs recapitulate the epigenetic features of human retinal development is unknown. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics over long-term human retinal and RO development. Our results showed that ROs recapitulated the human retinogenesis to a great extent, but divergent chromatin features were also discovered. We further reconstructed the transcriptional regulatory network governing human and RO retinogenesis in vivo. Notably, NFIB and THRA were identified as regulators in human retinal development. The chromatin modifications between developing human and mouse retina were also cross-analyzed. Notably, we revealed an enriched bivalent modification of H3K4me3 and H3K27me3 in human but not in murine retinogenesis, suggesting a more dedicated epigenetic regulation on human genome.
Cited by 75Open access
Л. К. Мошетова, Svetlana A. Usharova, С В Симонова et al. · Russian Journal of Clinical Ophthalmology · 2021
Impaired blood flow in various organs and tissues is a common cause of disabling disorders that even result in a lethal outcome. Despite an extremely rapid development of modern medicine, the rate of these disorders is still high thus emphasizing the importance of further detailed studies on this issue. In addition to systemic vascular diseases, local blood flow disturbances are also prevalent among population. These disturbances result from more significant blood flow disorders. Retinal vein occlusion is not an exclusion. Acute retinal vein occlusions account for more than half of ocular vascular diseases and may lead to extremely severe ophthalmic complications that result in poor vision, blindness, and reduced quality of life in both young and elderly patients. The diversity of clinical presentations, their severity, and clinical course make the diagnosis challenging thus altering the assessment of the prevalence of these diseases. Keywords: retinal vein occlusion, epidemiology, systemic vascular disorders, risk factors, retinal vessels. For citation: Moshetova L.К., Usharova S.А., Simonova S.V.,Turkina К.I. Epidemiology of retinal vein occlusions: state-of-the-art. Russian Journal of Clinical Ophthalmology. 2021;21(2):86–89. DOI: 10.32364/2311-7729-2021-21-2-86-89.
Cited by 2Open access
Tae-Hoon Kim, Taeyoon Son, David Le et al. · Scientific Reports · 2019
The hyaloid vascular system (HVS) is known to have an important role in eye development. However, physiological mechanisms of HVS regression and their correlation with developmental eye disorders remain unclear due to technical limitations of conventional ending point examination with fixed tissues. Here, we report comparative optical coherence tomography (OCT) and OCT angiography (OCTA) monitoring of HVS regression in wild-type and retinal degeneration 10 (rd10) mice. Longitudinal OCTA monitoring revealed accelerated regression of hyaloid vessels correlated with retinal degeneration in rd10. Quantitative OCT measurement disclosed significant distortions of both retinal thickness and the vitreous chamber in rd10 compared to WT mice. These OCT/OCTA observations confirmed the close relationship between HVS physiology and retinal neurovascular development. The distorted HVS regression might result from retinal hyperoxia or dopamine abnormality due to retinal remodeling in rd10 retina. By providing a noninvasive imaging platform for longitudinal monitoring of HVS regression, further OCT/OCTA study may lead to in-depth understanding of the physiological mechanisms of HVS regression in normal and diseased eyes, which is not only important for advanced study of the nature of the visual system but also may provide insights into the development of better treatment protocols of congenital eye disorders.
Cited by 16Open access
Shaojun Wang, Yi Sun, Jie Na et al. · Frontiers in Cell and Developmental Biology · 2025
Human embryonic stem cells (hESC)-derived retinal organoids are sophisticated <i>in vitro</i> systems for dissecting the complex dynamics of human retinal development. The formation of the human retina is a precisely organized process that depends on the regulated differentiation of retinal progenitor cells; however, many of the basic mechanisms remain to be explored. Here, using hESC-derived retinal organoids, we elucidated the temporal contribution of RAX2 to retinal development, with an emphasis on photoreceptor cells (PC) formation. The results were corroborated using human fetal retinal tissue at various gestational ages. Using CRISPR/Cas9-mediated gene knockout, we delineated the essential role of RAX2 in modulating PC specifications. <i>RAX2</i> deficiency significantly altered the expression of <i>PAX6</i> and <i>SOX2</i>, two essential regulators of retinogenesis. Our results suggested that RAX2 is significant in retinal development, underpinning its potential as a therapeutic target in related retinal disorders.
Cited by 0Open access
Domenico Grosso, Enrico Borrelli, Riccardo Sacconi et al. · Clinical ophthalmology · 2020
Chorioretinal folds (CRFs) are undulations of the choroid and overlying Bruch's membrane, retinal pigment epithelium and neurosensory retina. CRFs represent a clinical sign that is mandatory to investigate assuming their association with several ocular and extra-ocular disorders. Recent advances in retinal imaging have improved the characterization of CRFs. More importantly, retinal imaging may be useful to detect ocular complications secondary to chronic CRFs, including the development of choroidal neovascularization.
Cited by 22Open access
Nestĕrov Ap · PubMed · 1995
The pathogenesis of diabetic retinopathy includes the following components actual at a local level: diffuse retinal hypoxia leading to increase in the retina of anaerobic energy processes, development of local acidosis causing venous congestion, increased permeability of retinal capillaries and veins, impairment of the structure of vascular walls, development of foci of deep retinal hypoxia and of proliferative changes. These disorders develop in succession and mutually aggravate each other. A noticeable role belongs to deteriorated evacuation of the products of abnormal metabolism which depends on the existence of a solid barrier (pigmented epithelium, Bruch's membrane) between the retina and choroid and on the venous congestion and impaired liquid circulation in the vitreous body. A dichotomic type of division of the central retinal artery and absence of anastomoses between its branches facilitate the appearance of foci of retinal hypoxia. Local pathogenetic therapy of diabetic retinopathy should be aimed at removal of at least one out of three factors: hypoxia, acidosis, or venous congestion. This does not make less important the treatment of general metabolic disorders characteristic of diabetes mellitus.
Cited by 4
David J. Loftus, B. Girten · NASA Technical Reports Server (NASA) · 2002
The development of an implantable device consisting of an array of carbon nanotubes on a silicon chip for restoration of vision in patients with macular degeneration and other retinal disorders is presented. The use of carbon nanotube bucky paper for retinal cell transplantation is proposed. This paper is in viewgraph form.
Cited by 0
Girten, Beverly, Loftus, David · NASA STI Repository (National Aeronautics and Space Administration)
The development of an implantable device consisting of an array of carbon nanotubes on a silicon chip for restoration of vision in patients with macular degeneration and other retinal disorders is presented. The use of carbon nanotube bucky paper for retinal cell transplantation is proposed. This paper is in viewgraph form.
Cited by 0Open access