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1.
Eur Rev Med Pharmacol Sci ; 26(16): 5736-5744, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36066147

RESUMO

OBJECTIVE: The aim of the study was to quantify the macular vascular density and retinal thickness in the eyes of young myopic people with myopia without pathological changes using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this cross-sectional study, 160 eyes of 80 myopia subjects without pathological changes were classified into three groups: mild myopia (N=40 eyes), moderate myopia (N=66 eyes), and high myopia (N=54 eyes). Macular vascular density (VD), retinal thickness, area of the foveal avascular zone, the flow area of the outer retina and choriocapillaris (CC) were measured using OCTA. The effects of other confounding factors including axial length, the spherical equivalent, and some systemic factors (blood pressure, height, weight, etc.) were also considered. RESULTS: As the severity of myopia increases, the CC flow area decreased (p=0.029). The superficial VD in the temporal, superior, nasal, and inferior regions was significantly lower in high myopia group compared to moderate and low myopia groups (all p<0.001). With increasing myopia, a significant reduction of deep VD was found in the superior region of the macula (p=0.007). In the fovea, there was no difference in the superficial or deep VD across groups (p=0.268 and p=0.413, respectively). Parafoveal retinal thickness was thinnest in the high myopia group and thickest in the mild myopia group (all p<0.05). The fovea was thickest in the high myopia group and thinnest in the mild myopia group (p=0.030). CONCLUSIONS: In young myopic people without pathological changes, superficial VD and retinal thickness decreased with myopia progression, except in the fovea. The CC flow area decreased with increasing myopia.


Assuntos
Miopia , Tomografia de Coerência Óptica , Adulto , Angiografia/métodos , Estudos Transversais , Angiofluoresceinografia/métodos , Humanos , Densidade Microvascular , Miopia/patologia , Retina/diagnóstico por imagem , Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos
2.
Sci Rep ; 12(1): 15479, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104429

RESUMO

Pigs are becoming an important pre-clinical animal species for translational ophthalmology, due to similarities with humans in anatomical and physiological patterns. Different models of eye disorders have been proposed, and they are good candidates to assess biocompatibility/functionality of retinal prostheses. Electroretinography is a common tool allowing to gain information on retinal function, with several types of electroretinogram (ERG) been implemented including full field (ff-ERG), multifocal (mf-ERG) and pattern (p-ERG). p-ERG represents a valuable tool to monitor Retinal Ganglion Cells (RGCs) activity and can be used to calculate p-ERG spatial acuity. Unfortunately, scarce methodological data are available regarding recording/interpretation of p-ERG and retinal acuity in biomedical pigs yet enhancing knowledge regarding pig vision physiology will allow for more refined and responsible use of such species. Aim of this study was to record p-ERG in juvenile pigs to functionally assess visual acuity. Six female hybrid pigs underwent two p-ERG recording sessions at 16 and 19 weeks of age. Photopic ff-ERG were also recorded; optical coherence tomography (OCT) and histology were used to confirm retinal integrity. ff-ERG signals were repeatable within/across sessions. All p-ERG traces consistently displayed characterizing peaks, and the progressive decrease of amplitude in response to the increment of spatial frequency revealed the reliability of the method. Mean p-ERG spatial acuities were 5.7 ± 0.14 (16 weeks) and 6.2 ± 0.15 cpd (19 weeks). Overall, the p-ERG recordings described in the present work seem reliable and repeatable, and may represent an important tool when it comes to vision assessment in pigs.


Assuntos
Eletrorretinografia , Doenças Retinianas , Animais , Eletrorretinografia/métodos , Feminino , Humanos , Reprodutibilidade dos Testes , Retina/patologia , Doenças Retinianas/patologia , Suínos , Tomografia de Coerência Óptica , Regulador Transcricional ERG
3.
Brain Behav ; 12(9): e2741, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35996223

RESUMO

INTRODUCTION: Increasing evidence suggests Amyotrophic Lateral Sclerosis (ALS) as a widespread pathological process comprising nonmotor features like fatigue, mild sensory symptoms, cognitive decline, and visual impairment. Measurements of retinal nerve fiber layer (RNFL) thickness using Optical Coherence Tomography (OCT) may correlate with the neurodegeneration associated with ALS. In addition to RNFL thickness, other OCT parameters have been explored in the context of diagnosing ALS and predicting disease severity. In this study, we explore the possibility that OCT parameters of patients with ALS may differ significantly from those of healthy controls and thus serve as biomarkers for the disease and its progression. MATERIALS AND METHODS: Between 2010 and 2021, the PubMed and EMBASE databases were examined for English language literature. ALS severity was assessed using the revised ALS functional rating scale (ALSFRS-R). The pooled mean differences in RNFL thickness between ALS patients and controls were calculated using the Standard Mean Difference (Hedges's g) with a 95% confidence interval (CI) in STATA software version 16. RESULTS: Eleven studies were reviewed for data collection. RNFL thickness was not statistically significantly different between ALS patients (n = 412) and controls (n = 376) (Hedges's g = -0.22; 95% CI: -0.51 to 0.07, I2 = 73.04%, p = .14). However, the thickness of inner nuclear layer was significantly different between ALS patients and controls (Hedges's g = -0.38; 95% CI: -0.61 to 0.14, I2 = 14.85%, p = .00). CONCLUSION: Our meta-analysis found that RNFL thickness as a whole or by individual quadrants was not significantly different between ALS patients and controls while the inner nuclear layer (INL) was substantially thinner.


Assuntos
Esclerose Amiotrófica Lateral , Disfunção Cognitiva , Esclerose Amiotrófica Lateral/diagnóstico por imagem , Disfunção Cognitiva/patologia , Humanos , Retina/diagnóstico por imagem , Retina/patologia , Tomografia de Coerência Óptica/métodos
4.
Aging (Albany NY) ; 14(16): 6594-6604, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35980290

RESUMO

Aberrant neovascularization in the retina is an important threat to vision and closely related to several retinal diseases, such as wet form of age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. However, the pathogenesis remains largely unknown. MicroRNAs (miRNAs) have been demonstrated to play critical regulatory roles in angiogenesis. Therefore, we aimed to identify the key miRNAs that regulate retinal neovascularization and elucidate the potential underlying mechanisms. In the present study, we performed RNA sequencing of microRNAs in the retina and found that miR-375 was significantly downregulated in the retina of oxygen-induced retinopathy mice. In retinal microvascular endothelial cells (RMECs), overexpression of miR-375 inhibited cell proliferation and angiogenesis. Conversely, inhibition of miR-375 had the opposite effects. Moreover, our results showed that miR-375 negatively regulated the protein expression of JAK2 by inhibiting its translation. The promoting effects of anti-miR-375 on cell proliferation and angiogenesis were attenuated by an inhibitor of STAT3. These results indicate that miR-375 mitigates cell proliferation and angiogenesis, at least in part, through the JAK2/STAT3 pathway in RMECs, which implies an important underlying mechanism of retinal angiogenesis and provides potential therapeutic targets for retinal microangiopathy.


Assuntos
MicroRNAs , Neovascularização Retiniana , Animais , Proliferação de Células/genética , Células Endoteliais/metabolismo , Janus Quinase 2/metabolismo , Camundongos , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Retina/patologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Fator de Transcrição STAT3/metabolismo
5.
Retina ; 42(9): 1716-1728, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35994585

RESUMO

PURPOSE: This study analyses whether prematurity, retinopathy of prematurity (ROP), and associated factors lead to altered foveal shape in adulthood and whether these alterations are associated with visual acuity. METHODS: The Gutenberg Prematurity Eye Study is a German cohort study with a prospective ophthalmologic examination (participants aged 18-52 years) of individuals born preterm and full-term that were examined with spectral domain optical coherence tomography. Participants were grouped according to gestational age (GA) and postnatal ROP status. Multivariable linear regression analyses for foveolar retinal thickness, foveal hypoplasia, and posterior vitreous status were performed. RESULTS: A total of 755 eyes of 414 preterm and full-term individuals were included (aged 28.6 ± 8.6 years, 233 female individuals). Central foveal retinal thickness increased as GA decreased. The prevalence of foveal hypoplasia was 2% (control group), 9% (GA 33-36), 18% (GA 29-32), 48% (GA ≤28), 50% (ROP without treatment), and 82% of eyes (with ROP requiring treatment). In multivariable analyses, central foveal thickness was independently associated with GA and advanced stages of ROP requiring treatment while foveal hypoplasia was only associated with GA. Posterior vitreous was more frequently visible as partially detached in full-term than in preterm individuals. Lower distant-corrected visual acuity correlated with increased foveolar thickness (rho = 0.08; P = 0.03) and with foveal hypoplasia (rho = 0.15, P < 0.001). CONCLUSION: Our findings indicate that there are fetal origins affecting foveal shape, resulting in foveal hypoplasia potentially affecting the visual acuity in adulthood.


Assuntos
Nascimento Prematuro , Retina , Transtornos da Visão , Adolescente , Adulto , Feminino , Fóvea Central/diagnóstico por imagem , Fóvea Central/patologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Retina/diagnóstico por imagem , Retina/patologia , Retinopatia da Prematuridade/epidemiologia , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico por imagem , Transtornos da Visão/epidemiologia , Adulto Jovem
6.
Stem Cell Res Ther ; 13(1): 430, 2022 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987845

RESUMO

BACKGROUND: Advanced therapies using adult mesenchymal stromal cells (MSCs) for neurodegenerative diseases are not effectively translated into the clinic. The cross talk between the transplanted cells and the host tissue is something that, despite its importance, is not being systematically investigated. METHODS: We have compared the response of the mouse healthy retina to the intravitreal transplantation of MSCs derived from the bone marrow in four modalities: syngeneic, allogeneic, xenogeneic and allogeneic with immunosuppression using functional analysis in vivo and histology, cytometry and protein measurement post-mortem. Data were considered significant (p < 0.05) after nonparametric suitable statistical tests. RESULTS: Transplanted cells remain in the vitreous and are cleared by microglial cells a process that is quicker in allotransplants regardless of immunosuppression. All transplants cause anatomical remodelling which is more severe after xenotransplants. Xeno- and allotransplants with or without immunosuppression cause macro- and microglial activation and retinal functional impairment, being xenotransplants the most detrimental and the only ones that recruit CD45+Iba1-cells. The profile of proinflammatory cytokines changes in all transplantation settings. However, none of these changes affect the retinal ganglion cell population. CONCLUSIONS: We show here a specific functional and anatomical retinal response depending on the MSC transplantation modality, an aspect that should be taken into consideration when conducting preclinical studies if we intend a more realistic translation into clinical practice.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Retina/patologia , Células Ganglionares da Retina/patologia
7.
Harefuah ; 161(8): 523-525, 2022 Aug.
Artigo em Hebraico | MEDLINE | ID: mdl-35979573

RESUMO

INTRODUCTION: Alzheimer's disease is a neurodegenerative disease pathologically characterized by accumulation of abnormal amyloid-beta (Aß) and tau proteins. Research is currently focused on developing treatments to reduce the risk of developing or inhibiting disease progression. Therefore, there is a need to identify diagnostic tools for the initial stages of the disease. The neuropathological processes in Alzheimer's disease exist several decades before symptoms appear and can be identified by PET imaging or CSF analysis. Still, these methods are limited in availability and may be expensive and invasive, and there is therefore a need to develop accessible, inexpensive and non-invasive diagnostic tools. The retina is a component of the central nervous system. Changes in the retina can reflect the cerebral pathological process in Alzheimer's disease. Indeed, evidence of Aß plaques and abnormal tau proteins in the retina of Alzheimer's patients has been reported. The advantage of the retina is its accessibility for direct visualization by existing and non-invasive means. The following review will examine retinal changes that are suggested as possible biomarkers for Alzheimer's disease and discuss directions for future research in the field.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Diagnóstico Precoce , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Retina/diagnóstico por imagem , Retina/metabolismo , Retina/patologia , Proteínas tau/metabolismo
8.
Acta Neuropathol Commun ; 10(1): 118, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986368

RESUMO

Neuroinflammation is recognized as a key component of neurodegenerative disease. In glaucoma, a common neurodegenerative disease and the leading cause of irreversible blindness, the evidence for neuroinflammation in patients is lacking. Animal models have demonstrated significant pro-inflammatory activation of resident glia in the retina, as well as influx of blood-derived monocytes and pro-inflammatory factors. Confirmation of this in human donor tissue has been challenging due to a lack of well-preserved and well-characterized post-mortem tissue. To address this we utilize archived, wax embedded eyes fixed immediately following enucleation from living glaucoma patients. We compared glaucoma to control eyes (enucleated for uveal melanoma where the tumor did not impact the central retina or optic nerve). We performed immunolabelling for neurodegenerative and glial markers (CD45, CD163, IBA1, GFAP, Vimentin) which were quantified by high-resolution light microscopy and image analysis in FIJI. Glaucoma eyes demonstrated significant neural loss consistent with advanced neurodegeneration. IBA1 and GFAP were significantly increased in the retina and optic nerve head of the glaucomatous eyes indicating that significant neuroinflammation had occurred which support findings in animal models. Inflammation is a treatable symptom of many diseases and as such, identification of earlier inflammatory processes in glaucoma could be important for potential future treatment options.


Assuntos
Glaucoma , Doenças Neurodegenerativas , Animais , Glaucoma/patologia , Glaucoma/cirurgia , Humanos , Doenças Neurodegenerativas/patologia , Doenças Neuroinflamatórias , Nervo Óptico/patologia , Retina/patologia
9.
JCI Insight ; 7(18)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-35951427

RESUMO

Cub domain-containing protein 1 (CDCP1) is a protein that is highly expressed on the surface of many cancer cells. However, its distribution in normal tissues and its potential roles in nontumor cells are poorly understood. We found that CDCP1 is present on both human and mouse retinal pigment epithelial (RPE) cells. CDCP1-KO mice developed attenuated retinal inflammation in a passive model of autoimmune uveitis, with disrupted tight junctions and infiltrating T cells detected in RPE flat mounts from WT but not CDCP1-KO mice during EAU development. Mechanistically, we discovered that CDCP1 on RPE cells was upregulated by IFN-γ in vitro and after EAU induction in vivo. CD6 stimulation induced increased RPE barrier permeability of WT but not CDCP1-knockdown (CDCP1-KD) RPE cells, and activated T cells migrated through WT RPE monolayers more efficiently than the CDCP1-KD RPE monolayers. In addition, CD6 stimulation of WT but not the CDCP1-KD RPE cells induced massive stress fiber formation and focal adhesion disruption to reduce cell barrier tight junctions. These data suggest that CDCP1 on RPE cells interacts with CD6 on T cells to induce RPE cytoskeleton remodeling and focal adhesion disruption, which open up the tight junctions to facilitate T cell infiltration for the development of uveitis.


Assuntos
Pigmentos da Retina , Uveíte , Animais , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/metabolismo , Humanos , Inflamação/metabolismo , Camundongos , Retina/patologia , Pigmentos da Retina/metabolismo , Junções Íntimas/metabolismo , Uveíte/metabolismo , Uveíte/patologia
10.
Zool Res ; 43(5): 738-749, 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-35927396

RESUMO

Glaucoma is characterized by the progressive loss of retinal ganglion cells (RGCs), although the pathogenic mechanism remains largely unknown. To study the mechanism and assess RGC degradation, mouse models are often used to simulate human glaucoma and specific markers are used to label and quantify RGCs. However, manually counting RGCs is time-consuming and prone to distortion due to subjective bias. Furthermore, semi-automated counting methods can produce significant differences due to different parameters, thereby failing objective evaluation. Here, to improve counting accuracy and efficiency, we developed an automated algorithm based on the improved YOLOv5 model, which uses five channels instead of one, with a squeeze-and-excitation block added. The complete number of RGCs in an intact mouse retina was obtained by dividing the retina into small overlapping areas and counting, and then merging the divided areas using a non-maximum suppression algorithm. The automated quantification results showed very strong correlation (mean Pearson correlation coefficient of 0.993) with manual counting. Importantly, the model achieved an average precision of 0.981. Furthermore, the graphics processing unit (GPU) calculation time for each retina was less than 1 min. The developed software has been uploaded online as a free and convenient tool for studies using mouse models of glaucoma, which should help elucidate disease pathogenesis and potential therapeutics.


Assuntos
Glaucoma , Doenças dos Roedores , Animais , Contagem de Células/veterinária , Modelos Animais de Doenças , Glaucoma/patologia , Glaucoma/veterinária , Humanos , Camundongos , Retina/patologia , Células Ganglionares da Retina/patologia , Doenças dos Roedores/patologia
11.
Cytokine ; 158: 155996, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35988458

RESUMO

Colony-stimulating factor 2 (CSF2) is a potent cytokine that stimulates myeloid cells, such as dendritic cells and macrophages. We have been analyzing the roles of microglia in retinal degeneration through the modulation of inflammation in the eye, and examined the roles of CSF2 in this process. Both subunits of the CSF2 receptor are expressed in microglia, but no evidence suggesting the involvement of CSF2 in inflammation in the degenerating eye has been reported. We found that Csf2 transcripts were induced in the early phase of in vitro mouse adult retina culture, used as degeneration models, suggesting that CSF2 induction is one of the earliest events occurring in the pathology of retinal degeneration. The administration of CSF2 into the retina after systemic NaIO3 treatment increased the number of microglia. To examine the roles of CSF2 in retinal inflammation, we overexpressed CSF2 in retinal explants. Induction of CSF2 activated microglia and Müller glia, and the layer structure of the retina was severely perturbed. CC motif chemokine ligand 2 (Ccl2) and C-X-C motif chemokine ligand 10 (Cxcl10), both of which are expressed in activated microglia, were strongly induced by the expression of CSF2 in the retina. The addition of CSF2 to primary retinal microglia and the microglial cell lines MG5 and BV2 showed statistically significant increase in Ccl2 and Il1b transcripts. Furthermore, CSF2 induced proliferation, migration, and phagocytosis in MG5 and/or BV2. The effects of CSF2 on microglia were mild, suggesting that CSF2 induced strong inflammation in the context of the retinal environment.


Assuntos
Degeneração Retiniana , Animais , Quimiocinas/metabolismo , Inflamação/metabolismo , Ligantes , Camundongos , Microglia/metabolismo , Retina/patologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia
12.
Stem Cell Res Ther ; 13(1): 388, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35907890

RESUMO

BACKGROUND: Diabetic retinopathy, a major complication of diabetes mellitus, is a leading cause of sigh-loss in working age adults. Progressive loss of integrity of the retinal neurovascular unit is a central element in the disease pathogenesis. Retinal ischemia and inflammatory processes drive interrelated pathologies such as blood retinal barrier disruption, fluid accumulation, gliosis, neuronal loss and/or aberrant neovascularisation. Current treatment options are somewhat limited to late-stages of the disease where there is already significant damage to the retinal architecture arising from degenerative, edematous and proliferative pathology. New preventive and interventional treatments to target early vasodegenerative and neurodegenerative stages of the disease are needed to ensure avoidance of sight-loss. MAIN BODY: Historically, diabetic retinopathy has been considered a primarily microvascular disease of the retina and clinically it is classified based on the presence and severity of vascular lesions. It is now known that neurodegeneration plays a significant role during the pathogenesis. Loss of neurons has been documented at early stages in pre-clinical models as well as in individuals with diabetes and, in some, even prior to the onset of clinically overt diabetic retinopathy. Recent studies suggest that some patients have a primarily neurodegenerative phenotype. Retinal pigment epithelial cells and the choroid are also affected during the disease pathogenesis and these tissues may also need to be addressed by new regenerative treatments. Most stem cell research for diabetic retinopathy to date has focused on addressing vasculopathy. Pre-clinical and clinical studies aiming to restore damaged vasculature using vasoactive progenitors including mesenchymal stromal/stem cells, adipose stem cells, CD34+ cells, endothelial colony forming cells and induced pluripotent stem cell derived endothelial cells are discussed in this review. Stem cells that could replace dying neurons such as retinal progenitor cells, pluripotent stem cell derived photoreceptors and ganglion cells as well as Müller stem cells are also discussed. Finally, challenges of stem cell therapies relevant to diabetic retinopathy are considered. CONCLUSION: Stem cell therapies hold great potential to replace dying cells during early and even late stages of diabetic retinopathy. However, due to the presence of different phenotypes, selecting the most suitable stem cell product for individual patients will be crucial for successful treatment.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Diabetes Mellitus/patologia , Retinopatia Diabética/etiologia , Células Endoteliais/patologia , Humanos , Retina/patologia , Células-Tronco/patologia
13.
CNS Neurosci Ther ; 28(10): 1613-1623, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35851754

RESUMO

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach. Our study preliminarily explored the potential safety and effectiveness of Telitacicept following plasma exchange in the treatment of recurrent NMOSD. METHODS: This was a single-center, single-arm, open-label study enrolling eight patients with recurrent NMOSD in China. All patients received plasma exchange three times, followed by Telitacicept 240 mg every week for 46 times. The primary endpoint was the time of first recurrence after enrollment. Secondary end points included: changes in Expanded Disability Status Scale score, Optic Spinal Impairment Scale score, Hauser Ambulation Index, number of lesions on MRI, retinal nerve fiber layer thickness measured by optical coherence tomography, latency and amplitude of visual evoked potential, titer of AQP4 antibody, and immune parameters of blood. Safety was also assessed. The study was registered with Chictr.org.cn (ChiCTR1800019427). RESULTS: Eight eligible patients were enrolled. Relapse occurred in two patients (25%) and five patients (63%) remained relapse free after 48 weeks of treatment. The time to first recurrence was prolonged and the number of recurrences was reduced (p < 0.001, power of test = 1). One patient withdrew from the study due to low neutrophil count. No serious adverse events occurred. CONCLUSIONS: In this small, uncontrolled study, Telitacicept following plasma exchange has the potential to be a safe treatment for patients with recurrent NMOSD. It may prolong the recurrence interval and reduces the annual count of recurrences. A multicenter randomized controlled study with a larger sample is thus feasible and needed to further assess its safety and efficacy.


Assuntos
Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Potenciais Evocados Visuais , Humanos , Imunossupressores/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Troca Plasmática , Recidiva , Retina/patologia
14.
J Stroke Cerebrovasc Dis ; 31(9): 106644, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35849917

RESUMO

OBJECTIVES: Diffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers. MATERIALS AND METHODS: Retrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed. RESULTS: We included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038). CONCLUSIONS: In this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.


Assuntos
Oclusão da Artéria Retiniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nervo Óptico/diagnóstico por imagem , Reprodutibilidade dos Testes , Retina/patologia , Oclusão da Artéria Retiniana/diagnóstico por imagem , Oclusão da Artéria Retiniana/terapia , Estudos Retrospectivos
15.
Scanning ; 2022: 5038918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811761

RESUMO

In order to study the vascular density and retinal thickness of myopic children, a depth study was carried out on the basis of OCTA microscope. Through the methods of prospective cross-sectional research, statistical analysis, and basic data comparison, the research examination of myopia children under OCTA was successfully analyzed. There were significant differences in the density of superficial capillaries in the whole macular region, inner ring, temporal side of inner ring, and nasal side (P = 0.033, 0.024, 0.018, 0.032), and there was no significant difference in other ranges (P > 0.05). Macular fovea, as the most sensitive part of the retina, has pathological changes, which will also lead to serious negative effects on vision. The limitations of cross-sectional studies include the results of a relatively small sample size. After the study of OCTA in the macular region of children with myopia, it is related to the progressive atrophy of the retina and choroid in the macular region. When there are obvious pathological changes in the macular region, the thickness of the macular region becomes significantly thinner. We found that there was a positive correlation between retinal vascular density and retinal thickness in the fovea and above of myopia. The retinal thickness of the whole macular region, the inner ring and its four quadrants, and the outer ring and its four quadrants were positively correlated with SE (standard error) (all P < 0.05); Foveal ring retinal thickness was not associated with SE.


Assuntos
Macula Lutea , Miopia , Criança , Estudos Transversais , Humanos , Macula Lutea/patologia , Densidade Microvascular , Miopia/patologia , Estudos Prospectivos , Retina/diagnóstico por imagem , Retina/patologia , Tomografia de Coerência Óptica/métodos
16.
Genes (Basel) ; 13(7)2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35886051

RESUMO

Choroideremia is an X-linked recessive condition presenting in males, with progressive degeneration of retinal and choroidal tissues leading to progressive visual loss. Its pathological mechanism is due to alterations in the CHM gene that encodes for REP1, a protein required for prenylation of Rab by the Rab geranylgeranyl transferase (RGGT). Even though female carriers are predicted to be not affected by the disease, a wide phenotypic spectrum ranging from mild to severe cases has been reported in women. The reason why Choroideremia manifests in female carriers remains elusive. While X chromosome inactivation (XCI) skewing has been proposed as a leading putative mechanism, emerging evidence has shown that CHM could variably escape from XCI. We described a family with an initial clinical suspicion of Retinitis Pigmentosa in which a novel CHM pathogenic splicing variant was found by exome sequencing. The variant, initially found in the 63-year-old female presenting with impaired visual acuity and severe retinal degeneration, segregated in the 31-year-old daughter and the 37-year-old son, both presenting with fundus anomalies. mRNA studies revealed a shorter in-frame CHM isoform lacking exon 10. Molecular modeling of the ternary REP1/Rab/RGGT protein complex predicted significant impairing of REP1/Rab binding without alteration of REP1/RGGT interaction. We suggest that, in our female cases, the biallelic expression of CHM may have led to the production of both the mutant and wild type REP1. The mutant isoform, sequestrating RGGT, could reduce its available amount for Rab prenylation, thus exerting a dominant-negative effect. If confirmed with further studies and in large cohorts of female carriers, the here proposed molecular mechanism could help to explain the complexity of manifestation of Choroideremia in females.


Assuntos
Coroideremia , Degeneração Retiniana , Retinite Pigmentosa , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Coroideremia/diagnóstico , Coroideremia/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retina/patologia , Degeneração Retiniana/genética , Retinite Pigmentosa/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-35820353

RESUMO

To study the pathophysiological roles of the fatty acid-binding proteins (FABPs) within the retina, we performed; (1) immunolabeling of human retinas, wild type (WT) rat and mouse retinas, rat models for diabetic retinopathy (DR) and retinitis pigmentosa (RP) with anti-FABP3, FABP4, FABP5, FABP7, FABP8 and FABP12, (2) electroretinogram (ERG) measurements of WT and FABP4-deficient (Fabp4-/-) mice, (3) ELISA or gas chromatography measurements of plasma (P-) and vitreous (V-) levels of FABP4 and vascular endothelial growth factor A (VEGFA), and fatty acids (FAs) from patients with retinal vascular disease (RVD) including proliferative DR (PDR, n = 30) and retinal vein occlusion (RVO, n = 18) and non-RVD (n = 18). Within the human retina, diverse expressions of FABP3, FABP4, FABP7 and FABP8 were identified. In contrast, positive immunoreactivities toward only FABP4 and FABP12 were detected in the cases of rat and mouse retinas, and interestingly, the FABP4 labeling patterns for the WT, DR and RP rat retinas were different. The ERG amplitudes of Fabp4-/- mice were enhanced compared with those of WT mice. The concentrations of V-FABP4, V-VEGFA and total FAs were significantly higher in RVD patients than in non-PDR patients (P < 0.05). The V-FAs levels of each were significantly and positively correlated with V-FABP4 and V-VEGFA, although no significant correlation between vitreous (V-) and plasma (P-) FABP4, VEGFA and FAs were detected. The current study reveals that V-FAs appear to have significant roles in both retinal physiology as well as the pathogenesis of RVD with FABP4, which is commonly expressed within the retina in most species.


Assuntos
Retinopatia Diabética , Fator A de Crescimento do Endotélio Vascular , Animais , Retinopatia Diabética/patologia , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Humanos , Camundongos , Ratos , Retina/metabolismo , Retina/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Invest Ophthalmol Vis Sci ; 63(8): 4, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35816046

RESUMO

Purpose: In choroideremia (CHM) carriers, scotopic sensitivity was assessed by dark adapted chromatic perimetry (DACP) and outer retinal structure was evaluated by multimodal imaging. Methods: Nine carriers (18 eyes) and 13 healthy controls (13 eyes) underwent DACP testing with cyan and red stimuli. Analysis addressed peripapillary (4 test locations closest to the optic disc), macular (52 locations), and peripheral (60 locations outside the macula) regions. Responses were considered to be rod-mediated when cyan relative to red sensitivity was >5 dB. Fundus imaging included spectral domain optical coherence tomography (SD-OCT), short-wavelength (SW-AF), near-infrared (NIR-AF), ultrawide-field (200 degrees) pseudocolor fundus imaging, and quantitative (qAF) fundus autofluorescence. Results: Detection of the cyan stimulus was rod mediated in essentially all test locations (99.7%). In the macular and peripheral areas, DACP sensitivity values were not significantly different from healthy eyes. In the peripapillary area, sensitivities were significantly decreased (P < 0.05). SD-OCT imaging ranged from hyper-reflective lesions and discontinuities of the outer retinal bands to hypertransmission of signal. SW-AF and NIR-AF images presented with peripapillary atrophy in seven patients (14 eyes). Mosaicism was detectable in SW-AF images in seven patients and in NIR-AF images in five patients. Frank hypo-autofluorescence was visible in eight patients with distinct chorioretinopathy in seven patients. The qAF values were below the 95% confidence interval (CI) of healthy age-matched individuals in 12 eyes. Conclusions: Rod mediated scotopic sensitivity was comparable to that in control eyes in macular and peripheral areas but was decreased in the peripapillary area where changes in retinal structure were also most severe.


Assuntos
Coroideremia , Coroideremia/diagnóstico , Coroideremia/patologia , Angiofluoresceinografia/métodos , Fundo de Olho , Humanos , Retina/diagnóstico por imagem , Retina/patologia , Tomografia de Coerência Óptica/métodos , Testes de Campo Visual
19.
Invest Ophthalmol Vis Sci ; 63(8): 14, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35822950

RESUMO

Purpose: Semaphorin 3A (Sema3A) is a promising therapeutic target for macular edema in age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion (RVO). Anti-vascular endothelial growth factors (anti-VEGFs) are the current standard of care for many retinal diseases. This study investigated the Sema3A neutralizing antibody BI-X and/or anti-VEGF therapy (aflibercept) in an RVO mouse model. Treatment efficacy was examined and grouped by timing subsequent to the RVO mouse model induction: efficacy against the onset of intraretinal edema 1 day postinduction and protective effects at 7 days postinduction. Methods: We examined the changes in expression of Sema3A in the retina of an RVO mouse model. In addition, changes in expression of tumor necrosis factor (TNF)-α and semaphorin-related proteins (neuropilin-1 and plexin A1) in the retina upon treatment were analyzed by Western blotting. The effects of BI-X and/or aflibercept were evaluated using measures of retinal edema, blood flow, and thinning of the inner nuclear layer. Results: Induction of vein occlusion in the RVO mouse model significantly increased Sema3A expression in the retina, particularly in the inner nuclear layer. BI-X was effective as a monotherapy and in combination with anti-VEGF therapy, demonstrating a beneficial effect on intraretinal edema and retinal blood flow. Moreover, in the RVO mouse model, BI-X monotherapy normalized the changes in expression of TNF-α and semaphorin-related proteins. Conclusions: These findings support targeting Sema3A to treat intraretinal edema and retinal ischemia.


Assuntos
Edema Macular , Doenças Retinianas , Oclusão da Veia Retiniana , Inibidores da Angiogênese/uso terapêutico , Animais , Anticorpos Neutralizantes/farmacologia , Anticorpos Neutralizantes/uso terapêutico , Modelos Animais de Doenças , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Camundongos , Retina/patologia , Doenças Retinianas/patologia , Oclusão da Veia Retiniana/metabolismo , Semaforina-3A/metabolismo
20.
J Vis Exp ; (184)2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35786611

RESUMO

Retinitis pigmentosa (RP) is a rare and inherited retinal degenerative disease with a prevalence of approximately 1/4,000 people worldwide. The majority of RP patients have progressive photoreceptor degeneration leading to peripheral vision loss, night blindness, and finally, total blindness. To date, thousands of mutations in more than 90 genes have been reported to be associated with RP. Currently, there are few animal models available for all the affected genes and different types of mutations, which largely hampers the deciphering of the mechanisms underlying the gene/mutation pathology and limits treatment and drug development. Patient induced pluripotent stem cell (iPSC)-derived 3D retinal organoids (ROs) have provided a better system to model the human early-onset disease than cells and animals. In order to study RP, those patient-derived 3D retinal organoids were utilized to recapitulate the clinical phenotypes of RP. In the RP patient-derived ROs, Rhodopsin mislocalization was clearly displayed. Compared with other animal models, patient iPSC-derived retinal organoid models more closely recapitulated RP features and represent an ideal approach for investigating the disease pathogenesis and for drug development.


Assuntos
Células-Tronco Pluripotentes Induzidas , Degeneração Retiniana , Retinite Pigmentosa , Animais , Humanos , Organoides/patologia , Espécies Reativas de Oxigênio , Retina/patologia , Degeneração Retiniana/patologia , Retinite Pigmentosa/genética , Retinite Pigmentosa/patologia , Retinite Pigmentosa/terapia
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