ABSTRACT
Emerging evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR), preceding the development of microvascular abnormalities. Here, we assessed the impact of neuroinflammation on the retina of diabetic-induced rats. For this aim we have used a two-photon microscope to image the photoreceptors (PRs) at different eccentricities in unstained retinas obtained from both control (N = 4) and pathological rats (N = 4). This technique provides high-resolution images where individual PRs can be identified. Within each image, every PR was located, and its transversal area was measured and used as an objective parameter of neuroinflammation. In control samples, the size of the PRs hardly changed with retinal eccentricity. On the opposite end, diabetic retinas presented larger PR transversal sections. The ratio of PRs suffering from neuroinflammation was not uniform across the retina. Moreover, the maximum anatomical resolving power (in cycles/deg) was also calculated. This presents a double-slope pattern (from the central retina towards the periphery) in both types of specimens, although the values for diabetic retinas were significantly lower across all retinal locations. The results show that chronic retinal inflammation due to diabetes leads to an increase in PR transversal size. These changes are not uniform and depend on the retinal location. Two-photon microscopy is a useful tool to accurately characterize and quantify PR inflammatory processes and retinal alterations.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Animals , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/pathology , Rats , Diabetes Mellitus, Experimental/pathology , Male , Photoreceptor Cells, Vertebrate/pathology , Disease Models, Animal , Retina/pathology , Retina/diagnostic imaging , Microscopy, Fluorescence, Multiphoton/methods , Microscopy/methodsABSTRACT
KIAA0586 variants have been associated with a wide range of ciliopathies, mainly Joubert syndrome (JS, OMIM #616490) and short-rib thoracic dysplasia syndrome (SRTD, OMIM #616546). However, the hypothesis that this gene is involved with hydrolethalus syndrome (HSL, OMIM #614120) and orofaciodigital syndrome IV (OMIM #258860) has already been raised. Ciliopathies' clinical features are often overlapped despite differing in phenotype severity. Besides KIAA0586, HYLS1 and KIF7 are also known for being causative of ciliopathies, indicating that all three genes may have similar or converging genomic pathways. Overall, the genotypic and phenotypic spectrum of ciliopathies becomes wider and conflicting while more and more new variants are added to this group of disorders' molecular pot. In this case report we discuss the first Brazilian individual clinically diagnosed with hydrolethalus syndrome and molecular findings that demonstrate the role of KIAA0586 as a causative gene of a group of genetic disorders. Also, recent reports on individuals with intronic and exonic variants combined leading to ciliopathies support our patient's molecular diagnosis. At the same time, we discuss variable expressivity and overlapping features in ciliopathies.
Subject(s)
Abnormalities, Multiple , Cerebellum , Eye Abnormalities , Kidney Diseases, Cystic , Phenotype , Retina , Humans , Eye Abnormalities/genetics , Eye Abnormalities/pathology , Kidney Diseases, Cystic/genetics , Abnormalities, Multiple/genetics , Retina/abnormalities , Retina/pathology , Retina/metabolism , Cerebellum/abnormalities , Cerebellum/pathology , Ciliopathies/genetics , Male , Mutation , Female , Cell Cycle ProteinsABSTRACT
PURPOSE: We aimed to evaluate retinal nerve fiber and choroidal layer alterations in adolescents with anorexia nervosa using spectral-domain optical coherence tomography. METHODS: Thirty patients with anorexia nervosa and 30 healthy adolescents aged 12-18 years were included in this study. Their age, sex, body mass index, anorexia nervosa type, disease duration, and spectral-domain optical coherence tomography data were recorded. RESULTS: Central macular thickness and retinal nerve fiber layer thickness in the temporal and inferior regions were significantly lesser in patients with anorexia than in healthy controls (p<0.05). Moreover, significant choroidal thinning around the foveal and subfoveal regions in patients with anorexia was observed (p<0.05). In addition, a statistically significant relation between the increase in disease duration and the thinning of the inferior retinal nerve fiber layer was detected (p<0.05). CONCLUSION: The retinal nerve fiber layer and choroidal layer thicknesses were lesser in patients with anorexia than in healthy controls. Screening for retinal indices might prevent the development of irreversible retinal pathologies in adolescents with anorexia nervosa. In addition, thinning of the retinal nerve fiber and choroidal layers could reflect structural or functional changes in the brain of adolescents with anorexia nervosa.
Subject(s)
Anorexia Nervosa , Choroid , Nerve Fibers , Tomography, Optical Coherence , Humans , Anorexia Nervosa/diagnostic imaging , Anorexia Nervosa/pathology , Adolescent , Tomography, Optical Coherence/methods , Female , Choroid/diagnostic imaging , Choroid/pathology , Nerve Fibers/pathology , Case-Control Studies , Male , Child , Retina/diagnostic imaging , Retina/pathology , Body Mass Index , Reference Values , Statistics, NonparametricABSTRACT
Primary congenital glaucoma is a rare disease that occurs in early birth and can lead to low vision. Evaluating affected children is challenging and there is a lack of studies regarding color vision in pediatric glaucoma patients. This cross-sectional study included 21 eyes of 13 children with primary congenital glaucoma who were assessed using the Farnsworth D-15 test to evaluate color vision discrimination and by spectral domain optical coherence tomography to measure retinal fiber layer thickness. Age, visual acuity, cup-to-disc ratio and spherical equivalent data were also collected. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were measured and compared based on color vision test performance. Four eyes (19%) failed the color vision test with diffuse dyschromatopsia patterns. Only age showed statistical significance in color vision test performance. Global and sectional circumpapillary and macular retinal fiber layer thicknesses were similar between the color test outcomes dyschromatopsia and normal. While the color vision test could play a role in assessing children with primary congenital glaucoma, further studies are needed to correlate it with damage to retinal fiber layer thickness.
Subject(s)
Color Vision , Glaucoma , Tomography, Optical Coherence , Humans , Female , Male , Child , Cross-Sectional Studies , Tomography, Optical Coherence/methods , Glaucoma/congenital , Glaucoma/diagnostic imaging , Glaucoma/physiopathology , Glaucoma/pathology , Glaucoma/diagnosis , Child, Preschool , Color Vision/physiology , Visual Acuity , Adolescent , Color Vision Defects/physiopathology , Color Vision Defects/congenital , Color Perception/physiology , Retina/diagnostic imaging , Retina/pathology , Retina/physiopathology , Color Perception TestsABSTRACT
PURPOSE: In this study, we report a case of a young adult with X-linked juvenile retinoschisis (XLRS) with a rare pathogenic variant in the RS1 gene (c.522 + 2 T > A). METHODS: Ophthalmological evaluation, optical coherence tomography, full-field and multifocal electroretinograms and extensive genetic screening of genes related to visual loss were carried out in the participant. RESULTS: Clinical ophthalmological exams revealed a mild to moderate impairment of visual acuity. Retinal imaging showed bilateral foveal schisis, as well as normal a-wave, reduction in the b-wave amplitudes in dark- and light- adapted full-field electroretinograms, and abnormal oscillatory potentials. We found also diffuse amplitude reduction in multifocal electroretinogram arrays. A canonical splice variant was identified in the RS1 gene (c.522 + 2 T > A). CONCLUSION: A rare pathogenic variant of the RS1 gene was associated with diffuse retinal involvement (central and peripheral retina), probably in inner retina, and mild to moderate visual acuity impairment. The phenotypical characterization of rare mutations is relevant to provide information about the disease.
Subject(s)
Electroretinography , Retinoschisis , Young Adult , Humans , Retina/pathology , Retinoschisis/diagnosis , Retinoschisis/genetics , Mutation , Fovea Centralis/pathology , Eye Proteins/genetics , Tomography, Optical CoherenceABSTRACT
BACKGROUND: ATXN2 is the causative gene of spinocerebellar ataxia type 2 (SCA2) and has been implicated in glaucoma pathogenesis. Therefore, studying ocular changes in SCA2 could uncover clinically relevant changes. OBJECTIVE: The aim was to investigate optic disc and retinal architecture in SCA2. METHODS: We evaluated 14 patients with SCA2 and 26 controls who underwent intraocular pressure measurement, fundoscopy, and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We compared SD-OCT measurements in SCA2 and controls, and the frequency of glaucomatous changes among SCA2, controls, and 76 patients with other SCAs (types 1, 3, 6, and 7). RESULTS: The macula, peripapillary retinal nerve fiber and inner plexiform layers were thinner in SCA2 than in controls. Increased cup-to-disc ratio was more frequent in SCA2 than in controls and other SCAs. CONCLUSIONS: Ocular changes are part of SCA2 phenotype. Future studies should further investigate retinal and optic nerve architecture in this disorder.
Subject(s)
Macula Lutea , Optic Disk , Humans , Optic Disk/pathology , Retinal Ganglion Cells/pathology , Retina/diagnostic imaging , Retina/pathology , Macula Lutea/pathology , Tomography, Optical Coherence/methodsABSTRACT
To report a unique case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in a patient with positive serology for Bartonella, presenting with ocular signs and symptoms not attributable to other diseases. A 27-year-old woman presented with decreased visual acuity in both eyes. Multimodal fundus image analysis was performed. A color fundus photograph of both eyes revealed peripapillary and macular yellow-white placoid lesions. The fundus autofluorescence of both eyes demonstrated hypo- and hyperautofluorescence of the macular lesions. Fluorescein angiography showed early-stage hypofluorescence and late staining of placoid lesions in both eyes. Spectral domain optical coherence tomography (SD-OCT) of both eyes revealed irregular elevations in the retinal pigment epithelium with the disruption of the ellipsoid zone on the topography of macular lesions. At 3 months after the treatment initiation for Bartonella infection, the placoid lesions became atrophic and hyperpigmented, and SD-OCT revealed loss of both the outer retinal layers and retinal pigment epithelium on the topography of macular lesions in both eyes.
Subject(s)
Bartonella Infections , Retinal Diseases , White Dot Syndromes , Female , Humans , Adult , Retinal Diseases/diagnosis , Retina/pathology , White Dot Syndromes/pathology , Retinal Pigment Epithelium/diagnostic imaging , Retinal Pigment Epithelium/pathology , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Bartonella Infections/complications , Bartonella Infections/pathology , Acute DiseaseABSTRACT
OBJECTIVE: To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation. ANIMALS: Thirty-three client-owned German Spitz dogs were included. PROCEDURES: All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA-marker-based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced. RESULTS: Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod-mediated ERGs were unrecordable in all affected dogs tested, reduced cone-mediated responses were present in one animal at 3 months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well-preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study. CONCLUSION: We identified early-onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D.
Subject(s)
Dog Diseases , Retinal Degeneration , Dogs , Humans , Animals , Frameshift Mutation , Retinal Degeneration/genetics , Retinal Degeneration/veterinary , Retinal Degeneration/diagnosis , Retina/pathology , Retinal Cone Photoreceptor Cells , Electroretinography/veterinary , Mutation , Tomography, Optical Coherence/veterinary , Atrophy/pathology , Atrophy/veterinary , Pedigree , Dog Diseases/genetics , Dog Diseases/pathologyABSTRACT
Early life stress (ELS) is defined as a period of severe and/or chronic trauma, as well as environmental/social deprivation or neglect in the prenatal/early postnatal stage. Presently, the impact of ELS on the retina in the adult stage is unknown. The long-term consequences of ELS at retinal level were analyzed in an animal model of maternal separation with early weaning (MSEW), which mimics early life maternal neglect. For this purpose, mice were separated from the dams for 2 h at postnatal days (PNDs) 4-6, for 3 h at PNDs 7-9, for 4 h at PNDs 10-12, for 6 h at PNDs 13-16, and weaned at PND17. At the end of each separation period, mothers were subjected to movement restriction for 10 min. Control pups were left undisturbed from PND0, and weaned at PND21. Electroretinograms, visual evoked potentials, vision-guided behavioral tests, retinal anterograde transport, and retinal histopathology were examined at PNDs 60-80. MSEW induced long-lasting functional and histological effects at retinal level, including decreased retinal ganglion cell function and alterations in vision-guided behaviors, likely associated to decreased synaptophysin content, retina-superior colliculus communication deficit, increased microglial phagocytic activity, and retinal ganglion cell loss through a corticoid-dependent mechanism. A treatment with mifepristone, injected every 3 days between PNDs 4 and16, prevented functional and structural alterations induced by MSEW. These results suggest that retinal alterations might be included among the childhood adversity-induced threats to life quality, and that an early intervention with mifepristone avoided ELS-induced retinal disturbances.
Subject(s)
Retina , Stress, Psychological , Animals , Mice , Evoked Potentials, Visual , Maternal Deprivation , Mifepristone , Retina/pathology , Stress, Psychological/complicationsABSTRACT
In this case study, the authors describe peculiar bilateral cotton wool-like retinal lesions associated with macular edema in a patient with COVID-19 who was vaccinated with a single dose of AstraZeneca one month earlier. This patient had no pulmonary or systemic cardiovascular complications from COVID-19, as reported in other papers that found retinal lesions. However, the patient was diagnosed with idiopathic myopathy when discovering the SARS-CoV-2 infection. The patient was a 22-year-old white female with no previous history of morbidity, complaining of blurred vision in both eyes seven days after testing positive for SARS-CoV-2 by PCR (using nasal and oral swab) and confirmed through ELISA blood test (IgM positive). There was no ancillary test revealing diabetes mellitus. The patient presented with scattered whitish cotton wool-like lesions and a few hemorrhages on the posterior pole in fundus examination. On spectral domain optical coherence tomography (SD-OCT), there were hyperreflective lesions in the nerve fiber layer, ganglion cell layer, inner nuclear layer, and inner and outer plexiform layers at the site corresponding to the whitish cotton wool-like lesions in the posterior fundus photos. Moreover, the macula of both eyes had intraretinal and subretinal fluid, reversible with corticosteroid therapy. In conclusion, COVID-19 has been associated with capillary disorders at different target sites such as retina, lungs, and central nervous system. Similarly, vaccination against SARS-CoV-2 has been linked to retinal complications in the literature; however, cotton wool-like lesions have not yet been reported. There are many questions yet to be answered about the implications of COVID-19 infection and its vaccines.
Subject(s)
COVID-19 , Macular Edema , Humans , Female , Young Adult , Adult , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , COVID-19/diagnosis , SARS-CoV-2 , Retina/pathology , Tomography, Optical Coherence/methodsABSTRACT
Müller glial cells (MGCs), the main glial component of the retina, play an active role in retinal homeostasis during development and pathological processes. They strongly monitor retinal environment and, in response to retinal imbalance, activate neuroprotective mechanisms mainly characterized by the increase of glial fibrillary acidic protein (GFAP). Under these circumstances, if homeostasis is not reestablished, the retina can be severely injured and GFAP contributes to neuronal degeneration, as they occur in several proliferative retinopathies such as diabetic retinopathy, sickle cell retinopathy and retinopathy of prematurity. In addition, MGCs have an active participation in inflammatory responses releasing proinflammatory mediators and metalloproteinases to the extracellular space and vitreous cavity. MGCs are also involved in the retinal neovascularization and matrix extracellular remodeling during the proliferative stage of retinopathies. Interestingly, low-density lipoprotein receptor-related protein 1 (LRP1) and its ligand α2-macroglobulin (α2M) are highly expressed in MGCs and they have been established to participate in multiple cellular and molecular activities with relevance in retinopathies. However, the exact mechanism of regulation of retinal LRP1 in MGCs is still unclear. Thus, the active participation of MGCs and LRP1 in these diseases, strongly supports the potential interest of them for the design of novel therapeutic approaches. In this review, we discuss the role of LRP1 in the multiple MGCs activities involved in the development and progression of proliferative retinopathies, identifying opportunities in the field that beg further research in this topic area.Summary StatementMGCs and LRP1 are active players in injured retinas, participating in key features such as gliosis and neurotoxicity, neovascularization, inflammation, and glucose control homeostasis during the progression of ischemic diseases, such as proliferative retinopathies.
Subject(s)
Ependymoglial Cells , Low Density Lipoprotein Receptor-Related Protein-1 , Retinal Neovascularization , Humans , Ependymoglial Cells/metabolism , Glial Fibrillary Acidic Protein/metabolism , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Retina/metabolism , Retina/pathology , Retinal Neovascularization/metabolism , Retinal Neovascularization/pathologyABSTRACT
Alzheimer's disease (AD) is one of the most significant health challenges of our time, affecting a growing number of the elderly population. In recent years, the retina has received increased attention as a candidate for AD biomarkers since it appears to manifest the pathological signatures of the disease. Therefore, its electrical activity may hint at AD-related physiological changes. However, it is unclear how AD affects retinal electrophysiology and what tools are more appropriate to detect these possible changes. In this study, we used entropy tools to estimate the complexity of the dynamics of healthy and diseased retinas at different ages. We recorded microelectroretinogram responses to visual stimuli of different nature from retinas of young and adult, wild-type and 5xFAD-an animal model of AD-mice. To estimate the complexity of signals, we used the multiscale entropy approach, which calculates the entropy at several time scales using a coarse graining procedure. We found that young retinas had more complex responses to different visual stimuli. Further, the responses of young, wild-type retinas to natural-like stimuli exhibited significantly higher complexity than young, 5xFAD retinas. Our findings support a theory of complexity-loss with aging and disease and can have significant implications for early AD diagnosis.
Subject(s)
Alzheimer Disease , Aged , Aging , Alzheimer Disease/pathology , Animals , Disease Models, Animal , Entropy , Humans , Mice , Retina/pathologyABSTRACT
BACKGROUND: Diabetic retinopathy (DR) is a specific microvascular complication arising from diabetes, and its pathogenesis is not completely understood. tRNA-derived stress-induced RNAs (tiRNAs), a new type of small noncoding RNA generated by specific cleavage of tRNAs, has become a promising target for several diseases. However, the regulatory function of tiRNAs in DR and its detailed mechanism remain unknown. RESULTS: Here, we analyzed the tiRNA profiles of normal and DR retinal tissues. The expression level of tiRNA-Val was significantly upregulated in DR retinal tissues. Consistently, tiRNA-Val was upregulated in human retinal microvascular endothelial cells (HRMECs) under high glucose conditions. The overexpression of tiRNA-Val enhanced cell proliferation and inhibited cell apoptosis in HRMECs, but the knockdown of tiRNA-Val decreased cell proliferation and promoted cell apoptosis. Mechanistically, tiRNA-Val, derived from mature tRNA-Val with Ang cleavage, decreased Sirt1 expression level by interacting with sirt1 3'UTR, leading to the accumulation of Hif-1α, a key target for DR. In addition, subretinal injection of adeno-associated virus to knock down tiRNA-Val in DR mice ameliorated the symptoms of DR. CONCLUSION: tiRNA-Val enhance cell proliferation and inhibited cell apoptosis via Sirt1/Hif-1α pathway in HRMECs of DR retinal tissues.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Animals , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Endothelial Cells , Mice , Neovascularization, Pathologic/genetics , Retina/metabolism , Retina/pathology , Sirtuin 1/metabolismABSTRACT
BACKGROUND: Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.
Subject(s)
Neurodegenerative Diseases , Tomography, Optical Coherence , Humans , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/pathology , Retina/diagnostic imaging , Retina/pathology , Tomography, Optical Coherence/methodsABSTRACT
ABSTRACT Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.
RESUMO A avaliação estrutural do cérebro, feita por meio dos exames de neuroimagem, é a forma mais utilizada de ferramenta diagnóstica e de acompanhamento das doenças neurodegenerativas. Técnicas de imagem mais sofisticadas podem ser necessárias especialmente nas fases mais precoces, antes mesmo do surgimento de quaisquer sintomas, porém costumam ser caras e pouco acessíveis. Sendo assim, é de fundamental importância a busca de biomarcadores não invasivos, de fácil acesso e baixo custo, que possam ser utilizados para rastreio populacional e diagnóstico mais precoce. Nesse cenário, o número de estudos com ênfase em técnicas de imagem para avaliação estrutural da retina em pacientes com doenças neurodegenerativas tem aumentado nos últimos anos. A retina apresenta similaridade embriológica, histológica, bioquímica, microvascular e neurotransmissora com o córtex cerebral, tornando-se assim um biomarcador único e promissor nas doenças neurodegenerativas. A tomografia de coerência óptica é uma moderna técnica de imagem não invasiva que gera imagens seccionais bidimensionais de alta resolução e medidas volumétricas tridimensionais reprodutivas do disco óptico e da mácula. Essa tecnologia é amplamente utilizada na prática oftalmológica para o diagnóstico e o seguimento de diversas doenças oculares, como glaucoma, retinopatia diabética e degeneração macular relacionada à idade. A redução da espessura da camada de fibras nervosas da retina e das camadas de células ganglionares em pacientes com doenças neurodegenerativas foi demonstrada em diversos estudos clínicos nos últimos anos. Nesta revisão, abordamos as principais aplicações clínicas da tomografia de coerência óptica nas doenças neurodegenerativas e discutimos o seu papel como potencial biomarcador nessas afecções.
Subject(s)
Humans , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/diagnostic imaging , Tomography, Optical Coherence/methods , Retina/pathology , Retina/diagnostic imagingABSTRACT
INTRODUCTION: The objective of this investigation was to evaluate the effects of high-intensity light-emitting diode (LED) light from a curing device on the retinas of Wistar rats. METHODS: Six male Wistar rats were used, and their ocular structures were the focus of this study. During the photostimulation of each animal, the right eye of the animal, considered the control sample, was covered with a removable polyvinyl chloride cap, and the contralateral eye, the experimental sample, was exposed to high-intensity LED light, 3200 mW/cm2 (VALO Ortho; Ultradent Products, South Jordan, Utah) for 144 seconds from a distance of 30 cm. The animals were exposed to the LED light 3 times on the same day to investigate if any acute inflammatory changes in the retina occurred. Seven days after the photostimulation sessions, the animals were anesthetized and perfused with paraformaldehyde solution. After which, the eyes were resected and processed histologically. The histologic sections were analyzed stereologically and histomorphometrically to measure the parameters of the retina under investigation. RESULTS: There was a statistically significant increase in total retinal volume in the experimental group because of the increased volume of the ganglion cell layers, inner plexiform layers, outer nuclear layers, and the cone and rod extensions. There was no statistically significant difference in terms of density. However, there was a statistically significant increase in the nuclear area of the cells in all the studied layers in the group exposed to high-intensity LED light. In addition, hyperchromatic cells that are suggestive of pyknosis were observed. CONCLUSIONS: An acute but short protocol of exposure of high-intensity LED light to the eye caused morphometric alterations in the retinal structures, specifically in the nuclear area of the photosensitive cells.
Subject(s)
Light , Retina , Animals , Disease Models, Animal , Humans , Jordan , Male , Rats , Rats, Wistar , Retina/pathologyABSTRACT
PURPOSE: This study aimed to evaluate a cell therapy strategy with human neural precursor cells (hNPCs) to treat diabetic retinopathy (DR) in Wistar rats induced to diabetes by injecting streptozotocin. MATERIAL AND METHODS: The Wharton's jelly mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate to develop neurospheres and obtain the hNPCs. The animals were divided into three groups: non-diabetic (ND) n = four, diabetic without treatment (DM) n = nine, and diabetic with cell therapy (DM + hNPCs) n = nine. After 8 weeks of diabetes induction and DR characteristics installed, intravitreal injection of hNPCs (1 × 106 cell/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were conducted before and during diabetes and after cell therapy. Four weeks posttreatment, histopathological and immunohistochemistry analyses were performed. RESULTS: The repair of the retinal structures in the treated group (DM + hNPCs) was observed by increased thickness of neuroretinal layers, especially in the ganglion cell and photoreceptor layers, higher ERG oscillatory potentials (OPs) amplitudes, and transplanted hNPCs integration into the Retinal Pigment Epithelium. CONCLUSIONS: The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regenerating the neuroretinal tissue.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Neural Stem Cells , Animals , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/therapy , Diabetic Retinopathy/pathology , Diabetic Retinopathy/therapy , Humans , Rats , Rats, Wistar , Retina/pathologyABSTRACT
Combined hamartoma of the retina and retinal pigment epithelium is a rare, benign intraocular tumor. Hamartoma of the retina and retinal pigment epithelium has been described in the literature as a condition presenting with variable retinal damage, ranging from partial epiretinal involvement to complete distortion of the retinal layers and retinal pigment epithelium. We report the case of an 8-year-old girl presenting with longstanding strabismus who was diagnosed with Hamartoma of the retina and retinal pigment epithelium based on multimodal imaging assessment. We explored the particular imaging findings from studies using spectral-domain optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and fluorescein angiography.
Subject(s)
Hamartoma , Retinal Diseases , Child , Epithelium/pathology , Female , Fluorescein Angiography , Hamartoma/complications , Hamartoma/diagnostic imaging , Humans , Multimodal Imaging , Retina/pathology , Retinal Diseases/pathology , Retinal Pigment Epithelium/diagnostic imaging , Retinal Pigment Epithelium/pathology , Tomography, Optical Coherence/methodsABSTRACT
Idiopathic epiretinal membrane (iERM) is a fibrocellular proliferation on the inner surface of the retina, which leads to decreased visual acuity and even central visual loss. As iERM is associated to advanced age and posterior vitreous detachment, a higher prevalence is expected with increasing life expectancy and aging of the global population. Although various cell types of retinal and extra-retinal origin have been described in iERMs (Müller glial cells, astrocytes, hyalocytes, retinal pigment epithelium cells, myofibroblasts, and fibroblasts), myofibroblasts have a central role in collagen production and contractile activity. Thus, myofibroblast differentiation is considered a key event for the iERM formation and progression, and fibroblasts, Müller glial cells, hyalocytes, and retinal pigment epithelium have been identified as myofibroblast precursors. On the other side, the different cell types synthesize growth factors, cytokines, and extracellular matrix, which have a crucial role in ERM pathogenesis. In the present review, the major cellular components and their functions are summarized, and their possible roles in the iERM formation are discussed. By exploring in detail the cellular and molecular aspects of iERM, we seek to contribute for better understanding of this fibrotic disease and the origin of myofibroblasts, which may eventually drive to more targeted therapeutic approaches.
Subject(s)
Epiretinal Membrane , Ependymoglial Cells/pathology , Epiretinal Membrane/etiology , Fibrosis , Humans , Retina/pathology , Retinal Pigment Epithelium/pathologyABSTRACT
ABSTRACT Purpose To evaluate the retinal blood vascular network of the retinographies of patients with different grades of diabetic retinopathy. Methods Ninety Retinographies (MESSIDOR database) were used, with different grades of diabetic retinopathy divided into 4 groups: no retinopathy (n=23), grade one (n=20), grade two (n=20) and grade three (n=27) diabetic retinopathy. The grades of diabetic retinopathy were classified according to the number of microaneurysms, number of hemorrhages and the presence of neovascularization. The images were skeletonized and quantified by fractal methods: dimension of box-counting (Dbc) and information (Dinf). Results The means of Dbc values of groups were around 1.25, without statistically significant difference in the dimension values between groups for whole retina. There was also no statistical difference in Dinf values between groups, whose means ranged between 1.294 ± 0.013 (group of grade 1) and 1.3 ± 0.017 (group of grade 3). The retinographies were divided into regions of equal areas. The fractal values of some retinal regions showed statistical differences, but these differences were not enough to show the sensitivity of fractal methods in identifying diabetic retinopathy. Conclusion The fractal methods were not able to identify the different grades of diabetic retinopathy in retinographies.
RESUMO Objetivo Avaliar a rede vascular sanguínea da retina a partir de retinografias de pacientes com diferentes graus de retinopatia diabética. Métodos Foram utilizadas 90 retinografias (banco de dados MESSIDOR), com diferentes graus de retinopatia diabética divididas em quatro grupos: sem retinopatia (n=23), retinopatia diabética de grau um (n=20), grau dois (n=20) e grau três (n=27). Os graus de retinopatia foram classificados conforme o número de microaneurismas, número de hemorragias e presença de neovascularização. As imagens foram esqueletizadas e quantificadas pelos métodos fractais: dimensão da contagem de caixas e informação. Resultados As médias dos valores das dimensões de contagem de caixas para todos os grupos foram próximas a 1,25, sem diferença estatisticamente significativa nos valores das dimensões entre os grupos para retina inteira. Também não houve diferença estatística nos valores da dimensão de informação entre os grupos, cujas médias variaram entre 1,294 ± 0,013 (grupo do grau 1) e 1,3 ± 0,017 (grupo do grau 3). As imagens retinianas foram divididas em regiões de áreas iguais. Os valores fractais de algumas regiões retinais mostraram diferenças estatísticas, mas estas não foram suficientes para mostrar a sensibilidade dos métodos fractais na identificação da retinopatia diabética. Conclusão Os métodos fractais não foram capazes de identificar os diferentes graus de retinopatia diabética em retinografias.