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1.
Pyroptosis in the Retinal Neurovascular Unit: New Insights Into Diabetic Retinopathy.
Meng, C, Gu, C, He, S, Su, T, Lhamo, T, Draga, D, Qiu, Q
Frontiers in immunology. 2021;:763092
Abstract
Diabetic retinopathy (DR) is prevalent among people with long-term diabetes mellitus (DM) and remains the leading cause of visual impairment in working-aged people. DR is related to chronic low-level inflammatory reactions. Pyroptosis is an emerging type of inflammatory cell death mediated by gasdermin D (GSDMD), NOD-like receptors and inflammatory caspases that promote interleukin-1β (IL-1β) and IL-18 release. In addition, the retinal neurovascular unit (NVU) is the functional basis of the retina. Recent studies have shown that pyroptosis may participate in the destruction of retinal NVU cells in simulated hyperglycemic DR environments. In this review, we will clarify the importance of pyroptosis in the retinal NVU during the development of DR.
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2.
The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development.
Wagstaff, EL, Heredero Berzal, A, Boon, CJF, Quinn, PMJ, Ten Asbroek, ALMA, Bergen, AA
International journal of molecular sciences. 2021;(13)
Abstract
Early in vivo embryonic retinal development is a well-documented and evolutionary conserved process. The specification towards eye development is temporally controlled by consecutive activation or inhibition of multiple key signaling pathways, such as the Wnt and hedgehog signaling pathways. Recently, with the use of retinal organoids, researchers aim to manipulate these pathways to achieve better human representative models for retinal development and disease. To achieve this, a plethora of different small molecules and signaling factors have been used at various time points and concentrations in retinal organoid differentiations, with varying success. Additions differ from protocol to protocol, but their usefulness or efficiency has not yet been systematically reviewed. Interestingly, many of these small molecules affect the same and/or multiple pathways, leading to reduced reproducibility and high variability between studies. In this review, we make an inventory of the key signaling pathways involved in early retinogenesis and their effect on the development of the early retina in vitro. Further, we provide a comprehensive overview of the small molecules and signaling factors that are added to retinal organoid differentiation protocols, documenting the molecular and functional effects of these additions. Lastly, we comparatively evaluate several of these factors using our established retinal organoid methodology.
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Clinical Role of Smartphone Fundus Imaging in Diabetic Retinopathy and Other Neuro-retinal Diseases.
Pujari, A, Saluja, G, Agarwal, D, Sinha, A, P R, A, Kumar, A, Sharma, N
Current eye research. 2021;(11):1605-1613
Abstract
Purpose: In today's life, many electronic gadgets have the potential to become invaluable health care devices in future. The gadgets in this category include smartphones, smartwatches, and others. Till now, smartphone role has been highlighted on many occasions in different areas, and they continue to possess immense role in clinical documentation, clinical consultation, and digitalization of ocular care. In last one decade, many treatable conditions including diabetic retinopathy, glaucoma, and other pediatric retinal diseases are being imaged using smartphones.Methods: To comprehend this cumulative knowledge, a detailed medical literature search was conducted on PubMed/Medline, Scopus, and Web of Science till February 2021.Results: The included literature revealed a definitive progress in posterior segment imaging. From simple torch light with smartphone examination to present day compact handy devices with artificial intelligence integrated software's have changed the very perspectives of ocular imaging in ophthalmology. The consistently reproducible results, constantly improving imaging techniques, and most importantly their affordable costs have renegotiated their role as effective screening devices in ophthalmology. Moreover, the obtained field of view, ocular safety, and their key utility in non-ophthalmic specialties are also growing.Conclusions: To conclude, smartphone imaging can now be considered as a quick, cost-effective, and digitalized tool for posterior segment screenings, however, their definite role in routine ophthalmic clinics is yet to be established.
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Low luminance visual acuity as a clinical measure and clinical trial outcome measure: a scoping review.
Wood, LJ, Jolly, JK, Buckley, TM, Josan, AS, MacLaren, RE
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists). 2021;(2):213-223
Abstract
PURPOSE The measurement of standard visual acuity (VA) is the most well-known part of any ophthalmic examination to indicate visual function. Despite this, it is insensitive in detecting early disease changes. Therefore, other visual function tests have been developed including low luminance VA (LLVA) and low luminance deficit (LLD). This scoping literature review aims to summarise the current published applications of LLVA and LLD assessments to evaluate their utility as clinical markers and research outcome measures in a variety of ophthalmic conditions. RECENT FINDINGS Sixty-five peer-reviewed publications were included. LLVA was pioneered for use in geographic atrophy, a subtype of age-related macular degeneration, which remains the mainstay of its clinical application. However, other studies have reported additional useful applications in inherited retinal diseases including rare maculopathies and rod-cone dystrophies. Although there are some variations in testing methodology, use of the standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart with a 2.0 log unit neutral density filter is the most popular approach. The optimal testing luminance is still to be defined. SUMMARY Overall, LLVA is an earlier clinical marker of change in central retinal function than standard VA. It has been shown to be a risk factor for disease progression and a better indicator of a patient's level of everyday visual function. It is inexpensive and simple to implement using readily available standard ophthalmic equipment.
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VEGFR1 signaling in retinal angiogenesis and microinflammation.
Uemura, A, Fruttiger, M, D'Amore, PA, De Falco, S, Joussen, AM, Sennlaub, F, Brunck, LR, Johnson, KT, Lambrou, GN, Rittenhouse, KD, et al
Progress in retinal and eye research. 2021;:100954
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Abstract
Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.
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Management strategy and novel ophthalmological findings in neonatal severe hypertriglyceridemia: a case report and literature review.
El-Koofy, NM, Abdo, YA, El-Fayoumi, D, Esmael, AF, Elmonem, MA, Ezzeldin, Z
Lipids in health and disease. 2021;(1):38
Abstract
BACKGROUND Neonatal severe hypertriglyceridemia is rarely reported in the literature and there is no consensus for hypertriglyceridemia management at this age group. METHODS The index case is a 4-week-old male infant with severe hypertriglyceridemia accidentally discovered during a circumcision surgery. His clinical and genetic characteristics and his successful management strategy are described. Furthermore, a detailed ophthalmological examination of the proband was conducted at 3 and 6 months of age using Fourier-domain-optical coherence tomography. RESULTS Triglycerides level at presentation was extremely high 33,727 mg/dL (380.8 mmol/L). Two sessions of exchange blood transfusion on two consecutive days successfully reduced triglycerides to 382 mg/dL (4.3 mmol/L) with no adverse effects. The infant was discharged 3 days later. At discharge, the mother was advised to continue breastfeeding together with a medium-chain triglycerides formula. Satisfactory growth parameters and lipid profile values were obtained for a follow-up duration of 5 months with no reported attacks of acute pancreatitis. Lipoprotein lipase deficiency was confirmed by the detection of the LPL homozygous pathogenic variant c.805G > A; p.(Glu269Lys). Early corneal and macular lesions were detected and persisted on follow-up despite relatively good lipemic control. CONCLUSION This case highlights the importance of the early discovery of severe hypertriglyceridemia during the neonatal period, which is needed for prompt management and prevention of severe complications. Rationalized breastfeeding can be tolerated within the diet plan of the disease with satisfactory outcomes. To our knowledge, it is the first study reporting early corneal and macular affection by severe hypertriglyceridemia in a neonate. Prolonged follow-up is needed to determine the extent of ophthalmological lesions.
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Cell-Matrix Interactions in the Eye: From Cornea to Choroid.
Pouw, AE, Greiner, MA, Coussa, RG, Jiao, C, Han, IC, Skeie, JM, Fingert, JH, Mullins, RF, Sohn, EH
Cells. 2021;(3)
Abstract
The extracellular matrix (ECM) plays a crucial role in all parts of the eye, from maintaining clarity and hydration of the cornea and vitreous to regulating angiogenesis, intraocular pressure maintenance, and vascular signaling. This review focuses on the interactions of the ECM for homeostasis of normal physiologic functions of the cornea, vitreous, retina, retinal pigment epithelium, Bruch's membrane, and choroid as well as trabecular meshwork, optic nerve, conjunctiva and tenon's layer as it relates to glaucoma. A variety of pathways and key factors related to ECM in the eye are discussed, including but not limited to those related to transforming growth factor-β, vascular endothelial growth factor, basic-fibroblastic growth factor, connective tissue growth factor, matrix metalloproteinases (including MMP-2 and MMP-9, and MMP-14), collagen IV, fibronectin, elastin, canonical signaling, integrins, and endothelial morphogenesis consistent of cellular activation-tubulogenesis and cellular differentiation-stabilization. Alterations contributing to disease states such as wound healing, diabetes-related complications, Fuchs endothelial corneal dystrophy, angiogenesis, fibrosis, age-related macular degeneration, retinal detachment, and posteriorly inserted vitreous base are also reviewed.
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Congenital stationary night blindness: an update and review of the disease spectrum in Saudi Arabia.
Almutairi, F, Almeshari, N, Ahmad, K, Magliyah, MS, Schatz, P
Acta ophthalmologica. 2021;(6):581-591
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Abstract
Congenital stationary night blindness (CSNB) is a group of rare, mainly stationary disorders of the retina, resulting from dysfunction of several specific and essential visual processing mechanisms. The inheritance is often recessive and as such, CSNB may be more common among populations with a high degree of consanguinity. Here, we present a topic update and a review of the clinical and molecular genetic spectrum of CSNB in Saudi Arabia. Since a major review article on CSNB in 2015, which described 17 genes underlying CSNB, an additional four genes have been incriminated in autosomal recessive CSNB RIMS2, GNB3, GUCY2D and ABCA4. These have been associated with syndromic cone-rod synaptic disease, ON bipolar cell dysfunction with reduced cone sensitivity, CSNB with dysfunction of the phototransduction (Riggs type) and CSNB with cone-rod dystrophy, respectively. In Saudi Arabia, a total of 24 patients with CSNB were identified, using a combination of literature search and retrospective study of previously unpublished cases. Recessive mutations in TRPM1 and CABP4 accounted for the majority of cases (5 and 13 for each gene, respectively). These genes were associated with complete (cCSNB) and incomplete (icCSNB), respectively, and were associated with high myopia in the former and hyperopia in the latter. Four novel mutations were identified. For the first time, we describe the fundus albipunctatus in two patients from Saudi Arabia, caused by recessive mutation in RDH5 and RPE65, where the former in addition featured findings compatible with cone dystrophy. No cases were identified with any dominantly inherited CSNB.
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Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia-Induced Neurodegeneration in the Brain and Retina.
Pan, L, Cho, KS, Yi, I, To, CH, Chen, DF, Do, CW
Oxidative medicine and cellular longevity. 2021;:8377362
Abstract
Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).
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Systemic retinal biomarkers.
Ranchod, TM
Current opinion in ophthalmology. 2021;(5):439-444
Abstract
PURPOSE OF REVIEW Systemic retinal biomarkers are biomarkers identified in the retina and related to evaluation and management of systemic disease. This review summarizes the background, categories and key findings from this body of research as well as potential applications to clinical care. RECENT FINDINGS Potential systemic retinal biomarkers for cardiovascular disease, kidney disease and neurodegenerative disease were identified using regression analysis as well as more sophisticated image processing techniques. Deep learning techniques were used in a number of studies predicting diseases including anaemia and chronic kidney disease. A virtual coronary artery calcium score performed well against other competing traditional models of event prediction. SUMMARY Systemic retinal biomarker research has progressed rapidly using regression studies with clearly identified biomarkers such as retinal microvascular patterns, as well as using deep learning models. Future systemic retinal biomarker research may be able to boost performance using larger data sets, the addition of meta-data and higher resolution image inputs.