RESUMO
INTRODUCTION: This study aimed to investigate intraocular pressure (IOP)-independent factors associated with the progression of primary open-angle glaucoma (POAG) with IOP ≤15 mm Hg. METHODS: POAG patients with maximum IOP ≤15 mm Hg at the Kyoto University Hospital between January 2011 and August 2021 were retrospectively enrolled. We evaluated effects of various factors on the rate of mean deviation (MD) changes in the visual field (VF) examinations using a linear mixed model. These factors included hypertension, diabetes mellitus (DM), hyperlipidemia (HL), cardiovascular disease, arrhythmia, disc hemorrhage, sleep apnea syndrome, orthopedic diseases, and malignant tumors. RESULTS: In total, 98 eyes from 68 patients were included. The baseline MD was -9.74 ± 7.85 dB. The mean rate of MD change and IOP during the observation period were -0.28 ± 0.04 dB/year and 11.8 ± 1.0 mm Hg, respectively. Comorbidity of DM or HL showed a significant positive association with the rate of MD change (ß = 0.35, p = 0.0006 and ß = 0.18, p = 0.036, respectively) in the model adjusted for age, sex, axial length, mean IOP, and standard deviation of IOP during the observation period. However, no significant association of DM or HL was found after adjusting for central corneal thickness. CONCLUSION: This study suggests that DM or HL is associated with VF deterioration in glaucoma with lower IOP, but the association may be due to differences in IOP characteristics.
Assuntos
Progressão da Doença , Glaucoma de Ângulo Aberto , Pressão Intraocular , Campos Visuais , Humanos , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/diagnóstico , Feminino , Masculino , Pressão Intraocular/fisiologia , Estudos Retrospectivos , Fatores de Risco , Idoso , Pessoa de Meia-Idade , Campos Visuais/fisiologia , Seguimentos , Tonometria Ocular , Idoso de 80 Anos ou maisRESUMO
Bietti's crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-ß-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-ß-CyD. Our results suggest that HP-ß-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-ß-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-ß-CyD alone. Furthermore, the slow release of HP-ß-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-ß-CyD, and that HP-ß-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.
Assuntos
Colesterol , Distrofias Hereditárias da Córnea , Polissacarídeos Bacterianos , Doenças Retinianas , Humanos , Preparações de Ação Retardada/farmacologia , 2-Hidroxipropil-beta-Ciclodextrina/farmacologiaRESUMO
Acute kidney injury (AKI) is a life-threatening condition and often progresses to chronic kidney disease or the development of other organ dysfunction even after recovery. Despite the increased recognition and high prevalence of AKI worldwide, there has been no established treatment so far. The aim of this study was to investigate the renoprotective effect of Kyoto University substance 121 (KUS121), a novel valosin-containing protein modulator, on AKI. In in vitro experiments, we evaluated cell viability and ATP levels of proximal tubular cells with or without KUS121 under endoplasmic reticulum (ER) stress conditions. In in vivo experiments, the effects of KUS121 were examined in mice with AKI caused by ischemia-reperfusion injury. ER-associated degradation (ERAD)-processing capacity was evaluated by quantification of the ERAD substrate CD3delta-YFP. KUS121 protected proximal tubular cells from cell death under ER stress. The apoptotic response was mitigated as indicated by the suppression of C/EBP homologous protein expression and caspase-3 cleavage, with maintained intracellular ATP levels by KUS121 administration. KUS121 treatment suppressed the elevation of serum creatinine and neutrophil gelatinase-associated lipocalin levels and attenuated renal tubular damage after ischemia-reperfusion. The expression of inflammatory cytokines in the kidney was also suppressed in the KUS121-treated group. Valosin-containing protein expression levels were not altered by KUS121 both in vitro and in vivo. KUS121 treatment restored ERAD-processing capacity associated with potentiation of its upstream pathway, phosphorylated inositol-requiring enzyme-1α, and spliced X box-binding protein-1. In conclusion, these findings indicate that KUS121 can protect renal tubular cells from ER stress-induced injury, suggesting that KUS121 could be a novel and promising therapeutic compound for ischemia-associated AKI.NEW & NOTEWORTHY Novel findings of this study are as follows: 1) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.
Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Injúria Renal Aguda/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Apoptose , Degradação Associada com o Retículo Endoplasmático , Humanos , Isquemia/metabolismo , Camundongos , Traumatismo por Reperfusão/metabolismo , Proteína com Valosina/metabolismoRESUMO
PURPOSE: To investigate the association between the use of topical ß-blockers and subsequent asthma attacks in glaucoma patients with asthma. METHODS: This was a retrospective longitudinal cohort study using an administrative claims database. All patients aged 20 years or older who were registered in the health insurance claims database updated and managed by JMDC Inc. (Tokyo, Japan). Patients who were newly prescribed eye drops for glaucoma treatment were identified between 2011 and 2017. The patients with glaucoma were divided into two groups: ß-blocker users and non-ß-blocker users, based on the presence of a ß-blocker in the prescribed eye drops. We investigated whether the incidence of asthma attacks in patients with previously treated asthma differed between the two groups. RESULTS: We categorized 17,666 patients in the ß-blocker-user group and 12,609 patients in the non-ß-blocker-user group. A total of 580 patients in the ß-blocker group (3.28%) and 847 in the non-ß-blocker group (6.72%) underwent asthma treatment before the prescription of anti-glaucoma eye drops (P < 0.001). Furthermore, 94 patients in the ß-blocker-user group (0.53%) and 278 in the non-ß-blocker user group (2.20%) were undergoing current treatment for asthma (P < 0.001). The adjusted hazard ratios of asthma attacks were 0.73 (95% confidence interval, 0.46-1.16, P = 0.18) in patients with a history of asthma treatment and 1.22 (95% confidence interval, 0.56-2.70, P = 0.62) in patients with current asthma treatment, compared to the non-ß-blocker-user group. CONCLUSION: Our results clarified that several patients with asthma were prescribed topical ß-blockers for glaucoma treatment. However, asthma attacks may not be significantly attributed to topical ß-blockers, even in glaucoma patients under current asthma treatment. The administration of topical ß-blockers to asthma patients could be a treatment option in the absence of other treatment options, if adequate informed consent is obtained. Further studies are needed to draw a firm conclusion on this clinical question.
Assuntos
Asma , Glaucoma , Administração Tópica , Antagonistas Adrenérgicos beta/efeitos adversos , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Estudos de Coortes , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/epidemiologia , Humanos , Estudos Longitudinais , Estudos RetrospectivosRESUMO
Retinitis pigmentosa (RP) is an incurable retinal degenerative disease with an unknown mechanism of disease progression. Mer tyrosine kinase (MERTK), which encodes a receptor of the Tyro3/Axl/Mer family of tyrosine kinases, is one of the causal genes of RP. MERTK is reportedly expressed in the retinal pigment epithelium (RPE) and is essential for phagocytosis of the photoreceptor outer segment. Here, we established induced pluripotent stem cells (iPSC) from patients with RP having homozygous or compound heterozygous mutations in MERTK, and from healthy subjects; the RP patient- and healthy control-derived iPSCs were differentiated into RPE cells. Although cytoskeleton staining suggested that polarity may have been disturbed mildly, there were no apparent morphological differences between the diseased and normal RPE cells. The internalization of photoreceptor outer segments in diseased iPSC-RPE cells was significantly lower than that in normal iPSC-RPE cells. This in vitro disease model may be useful for elucidating the mechanisms of disease progression and screening treatments for the disease.
Assuntos
Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação , Fagocitose/fisiologia , Epitélio Pigmentado da Retina/metabolismo , Retinose Pigmentar/metabolismo , c-Mer Tirosina Quinase/genética , Adulto , Western Blotting , Técnicas de Cultura de Células , Diferenciação Celular , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Células-Tronco Pluripotentes Induzidas/patologia , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Segmento Externo das Células Fotorreceptoras da Retina/metabolismo , Retinose Pigmentar/genéticaRESUMO
PURPOSE: To assess the characteristics of glaucoma patients who received systemic or topical steroid treatment. METHODS: Patients who received steroid treatment were selected from a total of 4256 patients at our tertiary referral center of glaucoma management between August 2011 and October 2017. Clinical characteristics of the subjects were extracted from clinical records. To evaluate the factors influencing highest intraocular pressure during observation (max-IOP) or mean deviations (MDs) of visual field at the first and last visits, univariate and multivariate regression analyses were performed using a generalized estimating equation. RESULTS: Three hundred and eighty-two eyes of 196 patients were included in this study. The most frequent disease as the reason for steroid treatment was atopic dermatitis (58 eyes) followed by autoimmune diseases. The patients with atopic dermatitis were significantly younger (38.0 ± 11.2 years old, p < 0.001) and had lower MD (- 9.3 ± 9.1 dB at first visit, p = 0.01; - 10.6 ± 9.2 dB at last visit, p = 0.004) than those with other diseases. In multivariate regression analysis, age and MD at first visit, max-IOP, and atopic dermatitis were correlated with MD at last visit. CONCLUSIONS: The results of the present study suggest that patients with atopic dermatitis carry the risk of irreversible visual field loss even in youth. For earlier detection of high intraocular pressure, reinforcement of ophthalmological screening in management of atopic dermatitis should be recommended.
Assuntos
Dermatite Atópica , Glaucoma , Adolescente , Criança , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/epidemiologia , Humanos , Pressão Intraocular , Estudos Retrospectivos , Fatores de Risco , Esteroides , Campos VisuaisRESUMO
PURPOSE: To examine the morphology of Bruch's membrane opening (BMO), optic disc, and peripapillary atrophy (PPA) by scanning laser ophthalmoscopy (SLO) and spectral-domain optical coherence tomography (SD-OCT), and to determine their association with the axial length and visual field defects. METHODS: This was a cross-sectional study of 94 eyes of 56 subjects; 77 eyes were diagnosed with primary open-angle glaucoma and 17 eyes as normal. The margins of the optic disc were determined in the SLO images, and that of the BMO in the SD-OCT images. The ovality and area of the BMO and the optic disc were measured. The beta and gamma-PPA areas were also measured. The association of each parameter with the axial length and the mean deviation (MD) of the visual field tests was determined by generalized estimating equations (GEEs). RESULTS: The optic disc ovality was associated with the axial length and the MD (ß = -0.47, P = 7.6 × 10-4 and ß = 0.12, P = 0.040). The BMO ovality was not significantly associated with the axial length and the MD. The BMO area was associated with the axial length (ß = 0.30, P = 0.029). A larger BMO area was associated with a thinner BMO-based neuroretinal rim width (BMO-MRW) after adjustments for the MD (ß = -0.30, P = 2.1 × 10-4). The beta- and gamma-PPA areas were associated with the axial length (ß = 0.50, P = 7.4 × 10-5 and ß = 0.62, P = 4.2 × 10-6). CONCLUSIONS: The optic disc ovality was associated with both the axial length and MD, whereas BMO ovality was not. Attention should be paid to the influence of the axial length-related enlargement of the BMO.
Assuntos
Comprimento Axial do Olho/diagnóstico por imagem , Lâmina Basilar da Corioide/diagnóstico por imagem , Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular , Disco Óptico/patologia , Escotoma/diagnóstico , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Oftalmoscopia , Células Ganglionares da Retina , Estudos Retrospectivos , Escotoma/etiologia , Escotoma/fisiopatologia , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
BACKGROUND: Retinitis pigmentosa (RP), a neurodegenerative disease, is occasionally accompanied by choroidal neovascularization (CNV) and cystoid macular oedema. It is presently treated with repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. However, there are concerns regarding long-term inhibition of VEGF by the use of these agents, especially in cases involving neurodegenerative diseases, since VEGFs have a neuroprotective effect. Currently, there are no reports on the long-term safety of anti-VEGF therapy in patients with RP. CASE PRESENTATION: In this report, we describe the case of a 56-year-old female patient with CNV associated with RP who was treated with anti-VEGF therapy for 8 years. She had autosomal dominant RP with a heterozygous PRPH2 mutation (c.410G > A) and complained of metamorphopsia in her left eye. Examinations revealed CNV with serous retinal detachment. She was treated with as-needed injections for 2 years; however, she experienced a recurrence. Therefore, we switched to a bimonthly regimen that was continued for 6 years. In total, the patient received 34 injections of various types of anti-VEGFs over 8 years. No recurrences were noted during that time, and we have not detected any negative effects concerning the progression of visual field loss in comparison with the fellow eye. CONCLUSIONS: No negative effects related to the progression of visual field loss were observed during continuous treatment with anti-VEGF agents for 8 years in our patient.
Assuntos
Bevacizumab/administração & dosagem , Ranibizumab/administração & dosagem , Retinose Pigmentar/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Inibidores da Angiogênese/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Pessoa de Meia-Idade , Retinose Pigmentar/diagnóstico , Fatores de Tempo , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To investigate the dissociation of the Bruch's membrane opening (BMO) from the scleral canal opening (SO) of the optic disc. METHODS: In this prospective, cross-sectional, observational study, 101 eyes from 101 patients or suspected subjects of primary open angle glaucoma were included. Enhanced depth imaging spectral domain optical coherence tomography images along the long axis of the optic disc were used to visualize better the deep structures around the optic disc on both the temporal and nasal sides. The distances between the BMO and SO were measured at the temporal and nasal sides of the optic disc, and their correlations with age, axial length, intraocular pressure, disc size, disc ovality index, disc torsion degree, and visual field mean deviation were investigated. RESULTS: The temporal and nasal distances of BMO from SO correlated significantly with each other (R = 0.632, P < 0.0001). By multiple linear regression analysis, significant correlations were found for disc ovality index (temporal: ß = -0.691, P < 0.0001; nasal: ß = -0.420, P < 0.0001) and axial length (temporal: ß = 0.224, P = 0.002; nasal: ß = 0.310, P = 0.001). The other factors did not show any significant correlation. CONCLUSION: Locations of the SO at not only the temporal, but also the nasal side of the optic disc are nasally shifted from the BMO with optic disc tilting and axial length elongation in glaucomatous eyes, and are significantly correlated to each other. The nasal shift of the deep structures of the optic disc should be considered especially when assessing myopic eyes with optic disc tilt.
Assuntos
Lâmina Basilar da Corioide/patologia , Glaucoma de Ângulo Aberto/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Esclera/patologia , Anormalidade Torcional/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Comprimento Axial do Olho/patologia , Estudos Transversais , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica , Adulto JovemRESUMO
PURPOSE: We aimed to determine the sensitivity and specificity of the normative database of non-myopic and highly myopic eyes of the macular ganglion cell complex (mGCC) thickness embedded in the NIDEK RS-3000 spectral-domain optical coherence tomography (SD-OCT) for detecting early glaucoma in highly myopic eyes. METHODS: Forty-seven highly myopic eyes (axial length ≥26.0 mm) of 47 subjects were studied. The SD-OCT images were used to determine the mGCC thickness within a 9-mm diameter circle centered on the fovea. The sensitivity and specificity of the non-myopic database were compared to that of the highly myopic database for distinguishing the early glaucomatous eyes from the non-glaucomatous eyes. The mGCC scans were classified as abnormal if at least one of the eight sectors of the significance map was < 1 % of the normative thickness. RESULTS: Twenty-one eyes were diagnosed to be non-glaucomatous and 26 eyes to have early glaucoma. . The average mGCC thickness was significantly thinner (80.9 ± 8.5 µm) in the early glaucoma group than in the non-glaucomatous group (91.2 ± 7.5 µm; p <1 × 10(-4)). The sensitivity was 96.2 % and specificity was 47.6 % when the non-myopic database was used, and the sensitivity was 92.3 % and the specificity was 90.5 % when the highly myopic database was used. The difference in the specificity was significant (p < 0.01). CONCLUSIONS: The significantly higher specificity of the myopic normative database for detecting early glaucoma in highly myopic eyes will lead to fewer false positive diagnoses. The database obtained from highly myopic eyes should be used when evaluating the mGCC thickness of highly myopic eyes.
Assuntos
Bases de Dados Factuais , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Baixa Tensão/diagnóstico , Miopia Degenerativa/diagnóstico , Células Ganglionares da Retina/patologia , Adulto , Povo Asiático/etnologia , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Precoce , Feminino , Glaucoma de Ângulo Aberto/etnologia , Gonioscopia , Humanos , Pressão Intraocular , Japão/epidemiologia , Glaucoma de Baixa Tensão/etnologia , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/etnologia , Tamanho do Órgão , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia de Coerência Óptica , Testes de Campo Visual , Campos VisuaisRESUMO
Rationale: There have been meta-analyses that showed reduced retinal nerve fiber layer (RNFL) thickness, which is a surrogate marker of glaucoma, in patients with obstructive sleep apnea (OSA). However, the sample sizes in these reports were small (<300), and the mechanism of RNFL thinning in patients with OSA was not revealed.Objectives: To investigate the relationship of RNFL thickness with nocturnal hypoxemia or hypoxemic burden in a large-scale study.Methods: In this epidemiological study, 8,309 community residents were enrolled. The actigraphy-modified 3% oxygen desaturation index (acti-ODI3%) and cumulative percentage of sleep time with oxygen saturation <90% (acti-CT90) modified by objective sleep duration using actigraphy were measured. The hypoxemic burden is shown as acti-CT90. Circumpapillary RNFL thickness was determined using optical coherence tomography.Results: Multivariable logistic analysis models revealed that an increase in acti-CT90 was significantly associated with mean RNFL thinning after adjusting for several factors in participants without glaucoma diagnosed or treated previously (ß = -0.037; P = 0.009). There were significant differences in mean RNFL thickness among participants stratified according to acti-CT90 (>1.5 vs. ⩽1.5; P = 0.04). Although acti-ODI3% was significantly associated with acti-CT90 (ß = 0.72; P < 0.0001), acti-ODI3% was not significantly associated with mean RNFL thickness in the multivariable logistic analysis (ß = -0.011; P = 0.48). In addition, acti-CT90 was significantly associated with mean RNFL thickness both in the elderly (⩾60 yr; ß = -0.058; P = 0.002) and nonelderly (<60 yr; ß = -0.054; P = 0.007).Conclusions: Acti-CT90, but not acti-ODI3%, was associated with mean RNFL thinning in participants irrespective of age in the elderly or nonelderly. Further prospective studies are required to investigate whether the prevention of hypoxic burden, which was shown as acti-CT90 in this study, is favorable for RNFL thinning.
Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Disco Óptico , Humanos , Idoso , Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular , Campos Visuais , Glaucoma/epidemiologia , Glaucoma/diagnóstico , Tomografia de Coerência Óptica/métodos , Fibras Nervosas , Hipóxia/epidemiologiaRESUMO
Purpose: To evaluate the effect of trabeculectomy (Trab MMC) on visual field (VF) progression in eyes with glaucoma and high myopia. Patients and Methods: Patients diagnosed with primary open-angle glaucoma or exfoliation glaucoma who underwent Trab MMC as the first glaucoma surgery along with ≥3 VF tests preoperatively and postoperatively were enrolled. High myopia was defined as an axial length ≥26.5 mm. Postoperative reductions in intraocular pressure (IOP) were assessed by survival analysis using IOP measurements obtained preoperatively. The longitudinal trends of the outcome measures were evaluated using linear mixed models. Results: Thirty-five eyes of 32 patients were included in this study, including 22 eyes of 20 patients in non-highly myopic group and 13 eyes of 12 patients in highly myopic group. IOP decreased after Trab MMC, and the survival rate did not differ significantly in relation to axial length. Linear mixed-model analyses suggested that the inhibitory effects of Trab MMC on the rate of mean deviation (MD) changes were significant in the non-highly myopic group (-0.53 ± 0.15 dB/year preoperatively to -0.16 ± 0.13 dB/year postoperatively; P = 0.004), but not in the highly myopic group (-0.66 ± 0.19 dB/year preoperatively to -0.48 ± 0.18 dB/year postoperatively; P = 0.32). Conclusion: Trab MMC reduced IOP in both highly myopic and non-highly myopic eyes, and IOP reduction was very similar in both groups. The VF deterioration rate decreased in both groups, but the change was weaker and nonsignificant in the highly myopic group.
RESUMO
In retinitis pigmentosa (RP), photoreceptor degeneration leads to progressive visual field loss and visual impairment. Several therapeutic trials are ongoing aiming to establish effective treatments. Although functional evaluations are commonly used in clinical trials, residual ellipsoid zone (EZ) measurement on optical coherence tomography has been shown to be more sensitive to detect disease progression. Establishment of sensitive outcome measurement is essential to develop new therapeutic strategies. In the current study, we evaluated the progression rates of the disease in 76 eyes of 76 patients with RP, using the residual EZ length, ring-shaped macular hyperautofluorescent (AF), and visual field. Decrease rates measured by the residual EZ area and by the hyper-AF ring area were strongly positively correlated (P < 0.0001, r = 0.71). The reduction rates of the residual EZ length and hyper-AF ring radius were constant regardless of their baseline measurements. Faster annual reduction rates of the hyper-AF ring area or radius were significantly correlated with faster visual field progression (P = 0.03, r = 0.25 and P = 0.004, r = 0.33, respectively). These findings support the usage of morphological measurements such as EZ or hyper-AF ring measurements as outcome measurement for future clinical trials for RP.
Assuntos
Retinose Pigmentar , Testes de Campo Visual , Humanos , Tomografia de Coerência Óptica , Progressão da Doença , Acuidade Visual , Transtornos da VisãoRESUMO
Purpose: We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production. Methods: Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs. Results: BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time. Conclusions: BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.
Assuntos
Glaucoma , Degeneração Retiniana , Trifosfato de Adenosina/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose , Células HeLa , HumanosRESUMO
We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-D-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions.
Assuntos
N-Metilaspartato , Células Ganglionares da Retina , Animais , Antagonistas dos Receptores de Endotelina/farmacologia , Endotelina-1/metabolismo , Camundongos , N-Metilaspartato/metabolismo , Neuroproteção , Células Ganglionares da Retina/metabolismo , Tunicamicina/farmacologia , Proteína com Valosina/metabolismoRESUMO
We have established a stepwise method to differentiate induced pluripotent stem cells (iPSCs) into retinal pigment epithelium (RPE) (iPSC-RPE), which enables efficient isolation and purification of patient-derived iPSC-RPE cells with high quality. Here, we describe in detail the process of differentiating iPSCs into iPSC-RPE.
Assuntos
Células-Tronco Pluripotentes Induzidas , Diferenciação Celular , Humanos , Epitélio Pigmentado da RetinaRESUMO
OBJECTIVES: We investigated in vivo light-induced photoreceptor damage in retinitis pigmentosa (RP) using spectral-domain optical coherence tomography (SD-OCT) images. METHODS: We retrospectively reviewed patients with genetic diagnosis of EYS-associated RP. The outer nuclear layer (ONL) thickness under retinal vessels was measured on SD-OCT vertical scans. As a control, we measured adjacent ONL thickness 100 µm superior and inferior from the vessel. Same measurements were performed in healthy subjects. We calculated the ratio of ONL thickness under vessel divided by the average of adjacent ONL thickness and defined as ONL preservation ratio. In patients with RP, the length of ellipsoid zone (EZ) from the fovea was also measured with SD-OCT vertical scans. RESULTS: Thirty EYS-associated RP patients and 25 healthy subjects were included. In both groups, ONL thickness overshadowed by retinal vessels was not significantly different from that of adjacent area. However, ONL preservation ratio of RP was larger than that of healthy control in both superior and inferior retina (1.03 vs 0.97; p < 0.01, 1.15 vs 0.95; p < 0.01, respectively). In RP, ONL preservation ratio was significantly larger in the inferior retina than superior retina (p < 0.01). Furthermore, in RP patients, the EZ length from the fovea was always shorter in the inferior than superior retina and there was a significant difference (p < 0.01). CONCLUSIONS: Patients with EYS-associated RP exhibited inferior-dominant photoreceptor death and the relative ONL preservation under retinal vessels. These results suggest that longitudinal environment light exposure may be correlated with the photoreceptor death.
Assuntos
Retinose Pigmentar , Proteínas do Olho , Humanos , Retina , Vasos Retinianos/diagnóstico por imagem , Retinose Pigmentar/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
The effect of trabecular meshwork (TM)-targeted minimally invasive glaucoma surgery (MIGS) on the vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) has not been established. In this prospective, longitudinal study, we investigated changes in the deep vasculature following TM-targeted MIGS using AS-OCTA for open-angle glaucoma in 31 patients. AS-OCTA images of the sclera and conjunctiva at the nasal corneal limbus were acquired preoperatively and 3 months postoperatively, and the vessel densities (VDs) of the superficial (conjunctival) and deep (intrascleral) layers were calculated. The VDs before and after MIGS were compared, and the factors associated with the change in VD following MIGS were analyzed. The mean deep VD decreased from 11.98 ± 6.80% at baseline to 10.42 ± 5.02% postoperatively (P = 0.044), but superficial VD did not change (P = 0.73). The multivariate stepwise regression analysis revealed that deep VD reduction was directly associated with IOP reduction (P < 0.001) and preoperative IOP (P = 0.007) and inversely associated with preoperative deep VD (P < 0.001). The deep VD reduction following MIGS was significant in the successful group (21 eyes) (P = 0.032) but not in the unsuccessful group (10 eyes) (P = 0.49). The deep VDs assessed using AS-OCTA decreased following TM-targeted MIGS, especially in the eyes with good surgical outcomes.
Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Angiofluoresceinografia/métodos , Glaucoma/diagnóstico por imagem , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/diagnóstico por imagem , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Estudos Longitudinais , Estudos Prospectivos , Vasos Retinianos , Tomografia de Coerência Óptica/métodos , Malha Trabecular/diagnóstico por imagem , Malha Trabecular/cirurgiaRESUMO
OBJECTIVE: To visualize the macular ganglion cell layer (GCL) and measure its thickness in normal eyes and eyes with preperimetric glaucoma, using speckle noise-reduced spectral domain optical coherence tomography (SD-OCT). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Thirty-seven eyes of 37 patients with preperimetric glaucoma and 39 normal eyes of 39 volunteers. METHODS: Vertical and horizontal SD-OCT B-scan images were acquired with minimal speckle noise by using eye-tracking to obtain and average 50 B-scans at each identical location of interest. B-scan images were manually analyzed for GCL, retinal nerve fiber layer (RNFL), and inner plexiform layer shapes and thicknesses in the macula. MAIN OUTCOME MEASURES: Macular GCL images and thickness in normal eyes and in eyes with preperimetric glaucoma. RESULTS: The macular GCL was clearly seen on speckle noise-reduced SD-OCT images in normal eyes and eyes with preperimetric glaucoma. In each eye with preperimetric glaucoma, thinning of the macular GCL was visually apparent, particularly on vertical scans. The mean regional macular GCL was most severely thinned in the inferior perifoveal region, where its thickness was <70% of its normal thickness in 30 (81.1%) of the 37 eyes and <50% of its normal thickness in 13 (35.1%) of the 37 eyes. When the sensitivity and specificity for detecting abnormal thinning (outside the lower limit of 99% confidence interval [CI] for the means in the 39 normal eyes) in at least one 0.5-mm segment or sector were compared, the macular GCL on vertical B-scans exhibited higher sensitivity (81.1%) than the other layers on vertical B-scans (99% CI, 5.4%-59.5%; P = 0.00075-0.02100), the macular GCL (99% CI, 40.5%; P = 0.00027) on horizontal B-scans, the other layers (99% CI, 5.4%-48.6%; P<0.00048-0.00400) on horizontal B-scans, and circumpapillary RNFL automatically measured on SD-OCT (54.1%; P = 0.021), and scanning laser polarimetry with variable corneal compensation (24.3%; P = 0.00095). All the macular layers on both the vertical and horizontal B-scans and circumpapillary RNFL thickness exhibited comparable specificity (91.4-100.0%, statistically not different). CONCLUSIONS: Speckle noise-reduced SD-OCT imaging allowed clear visualization and measurement of the macular GCL, which was severely thinned in eyes with preperimetric glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Assuntos
Glaucoma/diagnóstico , Fibras Nervosas/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Testes de Campo Visual , Campos Visuais , Adulto JovemRESUMO
Optical coherence tomography angiography (OCTA) is a new technique for non-invasive imaging of blood vessels, allowing combined evaluation of both deep and surface vessels. The purpose of this study was to evaluate the post-trabeculectomy longitudinal changes in complete avascular area (CAA) of filtering blebs using anterior segment (AS-) OCTA and their association with surgical outcomes. This study included 57 eyes of 53 patients who had undergone trabeculectomy with mitomycin C. AS-OCTA images of filtering bleb were acquired at 3 and 6 months after trabeculectomy, and at 1 month in possible cases. CAAs, regions where complete blood flow was not depicted in AS-OCTA images, were evaluated for their presence, extent, and change over time. CAAs were detected in 37 eyes (65%) and 33 eyes (58%) at 3 and 6 months postoperatively, respectively. The extent of CAAs reduced over time after surgery in most cases. No parameters related to CAAs were significantly associated with surgical success (i.e., intraocular pressure (IOP) ≤ 12 mmHg and IOP reduction > 20% without medication). In conclusion, although it is difficult to predict surgical success by CAA itself, AS-OCTA may be useful for the objective evaluation of the vascularity of filtering blebs.