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1.
Adv Exp Med Biol ; 1186: 1-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654384

RESUMO

Pluripotent stem cell technology, including human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs), has provided a suitable platform to investigate molecular and pathological alterations in an individual cell type using patient's own cells. Importantly, hiPSCs/hESCs are amenable to genome editing providing unique access to isogenic controls. Specifically, the ability to introduce disease-causing mutations in control (unaffected) and conversely correct disease-causing mutations in patient-derived hiPSCs has provided a powerful approach to clearly link the disease phenotype with a specific gene mutation. In fact, utilizing hiPSC/hESC and CRISPR technology has provided significant insight into the pathomechanism of several diseases. With regard to the eye, the use of hiPSCs/hESCs to study human retinal diseases is especially relevant to retinal pigment epithelium (RPE)-based disorders. This is because several studies have now consistently shown that hiPSC-RPE in culture displays key physical, gene expression and functional attributes of human RPE in vivo. In this book chapter, we will discuss the current utility, limitations, and plausible future approaches of pluripotent stem cell technology for the study of retinal degenerative diseases. Of note, although we will broadly summarize the significant advances made in modeling and studying several retinal diseases utilizing hiPSCs/hESCs, our specific focus will be on the utility of patient-derived hiPSCs for (1) establishment of human cell models and (2) molecular and pharmacological studies on patient-derived cell models of retinal degenerative diseases where RPE cellular defects play a major pathogenic role in disease development and progression.


Assuntos
Células-Tronco Pluripotentes , Degeneração Retiniana , Epitélio Pigmentado da Retina , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas , Retina/patologia , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/patologia
2.
Adv Exp Med Biol ; 1186: 121-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654388

RESUMO

Human pluripotent stem cell (hPSC) technology has revolutionized the field of biology through the unprecedented ability to study the differentiation of human cells in vitro. In the past decade, hPSCs have been applied to study development, model disease, develop drugs, and devise cell replacement therapies for numerous biological systems. Of particular interest is the application of this technology to study and treat optic neuropathies such as glaucoma. Retinal ganglion cells (RGCs) are the primary cell type affected in these diseases, and once lost, they are unable to regenerate in adulthood. This necessitates the development of strategies to study the mechanisms of degeneration as well as develop translational therapeutic approaches to treat early- and late-stage disease progression. Numerous protocols have been established to derive RGCs from hPSCs, with the ability to generate large populations of human RGCs for translational applications. In this review, the key applications of hPSCs within the retinal field are described, including the use of these cells as developmental models, disease models, drug development, and finally, cell replacement therapies. In greater detail, the current report focuses on the differentiation of hPSC-derived RGCs and the many unique characteristics associated with these cells in vitro including their genetic identifiers, their electrophysiological activity, and their morphological maturation. Also described is the current progress in the use of patient-specific hPSCs to study optic neuropathies affecting RGCs, with emphasis on the use of these RGCs for studying disease mechanisms and pathogenesis, drug screening, and cell replacement therapies in future studies.


Assuntos
Diferenciação Celular , Células-Tronco Pluripotentes , Células Ganglionares da Retina , Glaucoma/terapia , Humanos , Neuropatologia/tendências , Doenças do Nervo Óptico/terapia , Células-Tronco Pluripotentes/citologia , Retina/citologia , Retina/patologia , Células Ganglionares da Retina/citologia
3.
Medicine (Baltimore) ; 98(38): e17223, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567980

RESUMO

The purpose of the study was to investigate the relationship between corneal deformation amplitude (DA), which is the amount of corneal displacement at highest degree of concavity measured by Corvis Scheimpflug Technology (ST), and various optic nerve head parameters in patients with primary open-angle glaucoma (POAG).Fifty-eight POAG patients were included in this observational study. For each patient, DA with Corvis ST, color optic disc photography, and optic nerve head imaging by enhanced depth imaging with a Heidelberg spectralis optical coherence tomography (OCT), Cirrus OCT, and Heidelberg retina tomograph (HRT) were obtained. Pearson correlation was used to analyze the relationship between DA and optic nerve head parameters before and after adjusting for age, intraocular pressure, central corneal thickness, and axial length.Corneal DA was negatively associated with lamina cribrosa (LC) depth (r = -0.390, P = .003) after adjusting for confounders. It showed positive relationship with parapapillary atrophy (PPA) area (r = 0.321, P = .046). In addition, the corneal DA was negatively correlated with cup volume (r = -0.351, P = .017) and mean cup depth (r = -0.409, P = .005) measured by HRT.Corneal DA is related with optic nerve head parameters in patients with POAG. Patients with lower corneal DA showed greater LC depth, greater cup area, deeper cup, and smaller PPA than those with higher corneal DA.


Assuntos
Córnea/patologia , Glaucoma de Ângulo Aberto/patologia , Disco Óptico/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Disco Óptico/diagnóstico por imagem , Retina/patologia , Tomografia de Coerência Óptica
4.
Dokl Biochem Biophys ; 486(1): 184-186, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367817

RESUMO

To perform optogenetic prosthetics of the retinal ganglion cell receptive field, a bicistronic genetic construct carrying the genes encoding the excitatory (channelrhodopsin-2) and inhibitory (Guillardia theta anion channelrhodopsin GtACR2) rhodopsins was created. A characteristic feature of this construct was the combination of these two genes with a mutant IRES insertion between them, which ensures the exact ratio of expression levels of the first and second genes in each transfected cell. Illumination of the central part of the neuron with light with a wavelength of 470 nm induced the action potential generation in the cell. Stimulation of the peripheral neuronal region with light induced the inhibition of action potential generation. Thus, using optogenetics methods, we simulated the ON-OFF interaction in the retinal ganglion cell receptive field. Theoretically, this construct can be used for optogenetic prosthetics of degenerative retina in the case of its delivery to the ganglion cells with lentiviral vectors.


Assuntos
Channelrhodopsins/genética , Optogenética/métodos , Retina/patologia , Células Ganglionares da Retina/metabolismo , Animais , Luz , Neurônios/citologia , Neurônios/metabolismo , Neurônios/efeitos da radiação , Ratos , Retina/efeitos da radiação , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/efeitos da radiação , Transfecção
5.
Semin Ophthalmol ; 34(6): 436-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309849

RESUMO

Purpose: To evaluate the efficacy and safety of oral eplerenone in cases of central serous chorioretinopathy (CSCR) refractory to photodynamic therapy (PDT). Methods: 19 patients with chronic CSCR and persistent subretinal fluid (SRF) were treated with oral eplerenone for 6 months, starting at a dose of 25 mg/day for 4 weeks and then 50 mg/day for 5 months. All patients underwent visual acuity measurement and optical coherence tomography (OCT), while fluorescein angiography was also performed at baseline, before treatment. Resolution of SRF, changes in retinal thickness and BCVA changes at month 6 and 12 post-treatment initiation were assessed. In addition, creatinine and electrolyte test was done on each patient every month for potential complications. Results: Two out of 19 cases were excluded, since one presented with hyperkaliemia 15 days after eplerenone intake and one with skin rash one day after the treatment initiation. At month 12, 88.2% of patients exhibited visual acuity improvement and 76.4% SRF resolution, while in 11.8% of patients SRF remained stable. Conclusions: This study has shown that eplerenone is safe and effective in cases of chronic CSCR, refractory to previous PDT.


Assuntos
Coriorretinopatia Serosa Central/tratamento farmacológico , Eplerenona/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Acuidade Visual/fisiologia , Administração Oral , Adulto , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/fisiopatologia , Corioide/patologia , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Retina/patologia , Tomografia de Coerência Óptica , Resultado do Tratamento
6.
J Agric Food Chem ; 67(30): 8348-8360, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31304751

RESUMO

We have recently demonstrated that tau hyperphosphorylation causes diabetic synaptic neurodegeneration of retinal ganglion cells (RGCs), which might be the earliest affair during the pathogenesis of diabetic retinopathy (DR). Thus, there is a pressing need to seek therapeutic agents possessing neuroprotective effects against tau hyperphosphorylation in RGCs for arresting the progression of DR. Here, using a well-characterized diabetes model of db/db mouse, we discovered that topical ocular application of 10 mg/kg/day of ginsenoside Rg1 (GRg1), one of the major active ingredients extracted from Panax ginseng and Panax notoginseng, ameliorated hyperphosphorylated tau-triggered RGCs synaptic neurodegeneration in diabetic mice. The neuroprotective effects of GRg1 on diabetic retinae were abrogated when retinal IRS-1 or Akt was suppressed by intravitreal injection with si-IRS-1 or topically coadministered with a specific inhibitor of Akt, respectively. However, selective repression of retinal GSK3ß by intravitreal administration of si-GSK3ß rescued the neuroprotective properties of GRg1 when Akt was inactivated. Therefore, the present study showed for the first time that GRg1 can prevent hyperphosphorylated tau-induced synaptic neurodegeneration of RGCs via activation of IRS-1/Akt/GSK3ß signaling in the early phase of DR. Moreover, our data clarify the potential therapeutic significance of GRg1 for neuroprotective intervention strategies of DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Ginsenosídeos/administração & dosagem , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Proteínas tau/metabolismo , Animais , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/tratamento farmacológico , Degeneração Neural/genética , Degeneração Neural/metabolismo , Panax notoginseng/química , Fosforilação , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/genética , Retina/patologia , Células Ganglionares da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas tau/genética
7.
BMC Ophthalmol ; 19(1): 160, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345183

RESUMO

PURPOSE: Central serous chorioretinopathy (CSCR) is a complex ocular entity that, in its chronic form, can lead to serious visual impairment and morphological damage to the retina. The aim of the current retrospective study was to evaluate the damage present after long-standing but resolved central serous chorioretinopathy and refer it to healthy individuals. Correlations between measurable factors-for example, duration of the disease, baseline retinal morphological parameters, or patient age and/or their degree of impairment-were also assessed. MATERIALS AND METHODS: The study group consisted of thirty-two eyes (13 female and 19 male, mean age 49.6 years SD +/- 10.5) with chronic central serous chorioretinopathy (mean duration 18.9 months SD +/- 15.4) in which complete resolution of subretinal fluid was achieved after subthreshold micropulse laser treatment. Inclusion criterion was a lack of subretinal fluid within the whole area of the central retina scanned by the spectral domain optical coherence tomography. The group was extracted out of 51 cases of chronic CSCR that were treated with that method. They were analyzed according to final best-corrected visual acuity and retinal morphological parameters as measured by spectral optical coherence tomography with angiography option (OCTA). Results were compared with the outcomes of a control group, which consisted of 40 eyes of healthy individuals with full distance visual acuity (0.0 logMAR, 1.0 Snellen) never treated with subthreshold micropulse laser. Statistical analysis included regarding correlation between final visual acuity and final central retinal thickness and retinal and functional parameters prior to treatment. RESULTS: Final best-corrected visual acuity after chronic central serous chorioretinopathy was 0.23 logMAR (0.6 Snellen) and central retinal thickness was 39.32 µm smaller than in controls. No correlation was found between final visual acuity and retinal thickness and duration of the disease, patient age, and baseline morphological retinal parameters. OCTA scans revealed impaired choriocapillaries flow signal even following resolution of the disease. CONCLUSION: Chronic central serous chorioretinopathy is a potentially damaging clinical entity that results in serious visual impairment, retinal thinning, and choroidal flow defects. Further research is needed to determine precisely the timepoint of this damage.


Assuntos
Coriorretinopatia Serosa Central/fisiopatologia , Retina/patologia , Transtornos da Visão/etiologia , Acuidade Visual/fisiologia , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/diagnóstico , Corioide/patologia , Doença Crônica , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Transtornos da Visão/diagnóstico , Transtornos da Visão/fisiopatologia
8.
Asia Pac J Ophthalmol (Phila) ; 8(4): 290-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31356365

RESUMO

PURPOSE: The aim of this study was to investigate factors predictive of subretinal fluid (SRF) resolution in Coats disease. DESIGN: Retrospective cohort study. METHODS: Institutional review board-approved review of patients diagnosed with Coats disease demonstrating SRF (stage 3-5) at a single center from November 1973 to July 2018 with comparison of eyes that had resolution of SRF to those in which SRF persisted. RESULTS: There were 177 cases (154 males, 87%) of Coats disease diagnosed at a mean age of 8 years. After a mean follow-up of 62 months, SRF resolved in 110 (62%) and persisted in 67 (38%) eyes. Comparison (resolved SRF vs persistent SRF) revealed classification as stage 3A [63 (57%) vs 20 (29%)], stage 3B [47 (43%) vs 40 (60%)], or stage 4 [0 (0%) vs 7 (11%)] (P < 0.001). Eyes with resolved SRF presented with fewer clock hours of telangiectasia (mean: 5 vs 7 clock hours, P < 0.001), light bulb aneurysms (mean: 5 vs 7 clock hours, P < 0.001), exudation (mean: 7 vs 10 clock hours, P < 0.001), and extent of SRF (mean: 7 vs 10 clock hours, P < 0.001). Factors predictive of SRF resolution included absence of iris neovascularization on fluorescein angiography [odds ratio 0.05 (95% confidence interval 0.01-0.60), P = 0.02], and less elevated SRF by ultrasonography [odds ratio 0.84 (95% confidence interval 0.76-0.95), P = 0.004). For every 1-mm decrease in SRF, likelihood of SRF resolution increased by 16%. CONCLUSIONS: Resolution of SRF was achieved in the majority of eyes (62%) with stage 3 to 5 Coats disease. Predictors of SRF resolution included lack of neovascularization on fluorescein angiography and less elevation of SRF by ultrasonography.


Assuntos
Angiofluoresceinografia/métodos , Retina/patologia , Telangiectasia Retiniana/diagnóstico , Líquido Sub-Retiniano/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Fundo de Olho , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/patologia , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
9.
Graefes Arch Clin Exp Ophthalmol ; 257(9): 1897-1913, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327036

RESUMO

PURPOSE: Putative roles of long non-coding RNAs (lncRNAs) as indicators for diabetic retinopathy (DR) and associated complications are beginning to emerge. We aimed to evaluate a panel of circulating hyperglycemia-related lncRNAs: RNCR2, NEAT2, CDKN2B-AS1, and PVT1 in type 2 diabetes patients with/without DR and to correlate their levels with the clinical characteristics and response to aflibercept intravitreal injection in terms of visual acuity (VA) improvement, central macular thickness (CMT) decline, and macular edema resolution after 4 weeks of the initial injection. METHODS: Pre-treatment plasma relative expression levels of the specified lncRNAs were quantified in 130 consecutive patients with diabetes (75 and 55 with/without DR, respectively) and 108 controls using quantitative real-time PCR. RESULTS: One month after aflibercept injection, significant reductions in CMT and VA were observed in DR cohorts. The four lncRNAs were over-expressed in DM compared with those in controls. However, downregulated baseline plasma levels of RNCR2 and NEAT2 were observed in glycemic-controlled DR patients. None of the lncRNAs showed a correlation with the severity of retinopathy or drug response. CONCLUSION: Though circulating levels of the analyzed lncRNAs did not show an association with DR progression or aflibercept therapy response, the expression pattern demonstrated good diagnostic performance in differentiating DM from controls and DR.


Assuntos
Retinopatia Diabética/sangue , RNA Longo não Codificante/sangue , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/genética , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA/genética , RNA Longo não Codificante/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Retina/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
11.
Rev Med Chil ; 147(4): 522-526, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344217

RESUMO

Alport syndrome is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities. We report two men with Alport syndrome. Both had chronic kidney disease and consulted for long-term loss of visual acuity. One had auditory abnormalities. On the ophthalmological examination, both had anterior lenticonus and one had dot or fleck retinopathy. Those findings are described in up to 50% and 70% of men with X-linked Alport syndrome, respectively. Both patients had a family history of Alport syndrome or suggestive signs and symptoms.


Assuntos
Oftalmopatias/patologia , Nefrite Hereditária/patologia , Adulto , Oftalmopatias/diagnóstico , Oftalmopatias/fisiopatologia , Perda Auditiva Neurossensorial , Humanos , Masculino , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/fisiopatologia , Retina/patologia , Tomografia de Coerência Óptica , Tonometria Ocular , Acuidade Visual
12.
Semin Ophthalmol ; 34(4): 303-311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31158044

RESUMO

Amblyopia refers to visual impairment resulting from perturbations in visual experience during visual development, typically secondary to strabismus, uncorrected refractive error, and/or deprivation. Amblyopia has traditionally been considered a cortical disease, but the depth of our understanding of this complex neurodevelopmental condition is limited by our ability to appreciate structural pathophysiology in the visual pathway. Recent advances in Optical Coherence Tomography (OCT) have facilitated numerous studies of the structural changes in the retina and optic nerve, thereby expanding our appreciation for the pathogenesis of this condition. In this review, we summarize findings from studies evaluating retinal, retinal nerve fiber layer, and choroidal thickness changes in patients with amblyopia. Focusing on the largest and most recent studies, we discuss common limitations and confounding variables in these studies. We summarize recent advances in ocular imaging technology and reconcile the findings of early histological reports with those of structural OCT in amblyopia.


Assuntos
Ambliopia/diagnóstico por imagem , Corioide/patologia , Técnicas de Diagnóstico Oftalmológico , Retina/patologia , Tomografia de Coerência Óptica/métodos , Ambliopia/patologia , Humanos , Fibras Nervosas/patologia
13.
Ophthalmologica ; 242(2): 113-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163427

RESUMO

PURPOSE: To evaluate the effects of repeated intra-silicone oil (SO) injections of methotrexate (MTX) on the outcomes of surgery for rhegmatogenous retinal detachment (RRD) with grade C proliferative vitreoretinopathy (PVR-C). METHODS: In this prospective pilot case series, eyes with RRD and PVR-C underwent pars plana vitrectomy and intraocular injection of SO. At the conclusion of the procedure, 250 µg of MTX was injected into the SO-filled vitreous cavity. Intra-SO injection was repeated at weeks 3 and 6; the minimum follow-up period was 6 months. The main outcome measure was retinal reattachment rate. RESULTS: Eleven eyes of 11 patients (mean age, 52.73 ± 18.01 years) were included. The mean follow-up period was 9 ± 3 months (range, 6-15 months). Total retinal detachment with anterior and/or posterior PVR-C was present in all eyes before surgery. Mean preoperative best-corrected visual acuity (BCVA) was 2.62 ± 0.04 logMAR. All operated eyes exhibited retinal reattachment posterior to the equator during the follow-up period. Mean postoperative BCVA was significantly improved to 1.02 ± 0.51 logMAR (p = 0.003). No ocular or systemic side effects were observed. CONCLUSION: Repeated intra-SO injection of MTX as an adjunctive therapy for RRD complicated by PVR showed promising results and was not associated with adverse effects. Further studies are needed to confirm its possible beneficial effects on the final anatomic and functional outcomes in these cases.


Assuntos
Metotrexato/administração & dosagem , Descolamento Retiniano/terapia , Óleos de Silicone , Acuidade Visual , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tamponamento Interno , Feminino , Humanos , Imunossupressores/administração & dosagem , Injeções Intraoculares , Fotocoagulação a Laser , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Retina/patologia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Tomografia de Coerência Óptica , Resultado do Tratamento , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/diagnóstico , Adulto Jovem
14.
Indian J Ophthalmol ; 67(7): 1095-1100, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31238419

RESUMO

Purpose: Diagnosis of choroidal neovascular membrane (CNVM) is difficult in chronic central serous chorioretinopathy (CCSC) due to overlapping features of both on conventional dye angiography. Optical coherence tomography angiography (OCTA) allows a quick and noninvasive detection of CNVM in these eyes. We compared the fluorescein angiography (FA) features of CNVM with those of OCTA to assess the role of FA in detecting CNVM in CCSC eyes. Methods: Patients with CCSC undergoing FA, spectral domain (SD)-OCT, and OCTA were identified (March 2015-June 2015). Four retina specialists individually reviewed FA images (without OCTA and SD-OCT) to determine whether CNVM was present. In parallel, two other retina specialists reviewed all images (FA/SD-OCT/OCTA) for CCSC features and confirmed whether CNVM was present using OCTA as the gold standard. The inter- and intraobserver variability was measured by Kappa (k) coefficient. The FA features of CNVM were compared and correlated with those on OCTA. Results: Of 43 eyes (26 patients, mean age 45.6 ± 8.5 years, all males), a definite CNVM (detected by OCTA) was present in nine (20.9%) eyes. FA alone detected CNVM in 13 (30.2%) eyes [sensitivity 44.4% (95% confidence interval (CI): 11.9-76.9), specificity 73.5% (95% CI: 58.7-88.3), positive and negative predictive values 30.8% and 83.3%, respectively, and accuracy 67.44% (95% CI: 53.4-81.4)]. Conclusion: When compared with OCTA, the FA was unable to characterize CNVM in CCSC (with a very low sensitivity and moderate specificity) as none of the specific dye leakage patterns on FA correlated with CNVM seen on OCTA, limiting its usefulness and accuracy in detecting CNVM in these eyes.


Assuntos
Coriorretinopatia Serosa Central/complicações , Corioide/irrigação sanguínea , Neovascularização de Coroide/diagnóstico , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , Coriorretinopatia Serosa Central/diagnóstico , Corioide/patologia , Neovascularização de Coroide/etiologia , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Retina/patologia , Estudos Retrospectivos
15.
Indian J Ophthalmol ; 67(7): 1121-1126, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31238425

RESUMO

Purpose: To report the prevalence of pachydrusen and their relationship with subfoveal choroidal thickness (SFCT) and large choroidal vessel layer thickness (SF-LCVT) in eyes with polypoidal choroidal vasculopathy (PCV) and their fellow eyes. Methods: The case records of 50 patients (99 eyes; 59 PCV and 40 fellow eyes) were retrospectively analyzed for the presence of pachydrusen and other drusen types such as soft drusen. The diagnosis was established using colour fundus photography and optical coherence tomography (OCT). SFCT and SF-LCVT were measured and correlated with the different types of drusen. Results: The mean age of the study cohort was 62.26 ± 10.67 years and included 27 males and 23 females. Pachydrusen and soft drusen were seen in 14 (PCV: 8 and fellow eyes: 6) and 8 eyes (PCV: 2 and fellow eyes: 6) respectively. The mean SFCT and SF-LCVT in the eyes with and without pachydrusen was not significanty different (280.29 ± 103.11 µ vs. 292.63 ± 87.17 µ; P = 0.63 and 180.57 ± 59.20 vs. 173.73 ± 54.86 µ; P = 0.67, respectively). The pachydrusen were most commonly located near the vascular arcades and showed scattered distribution pattern. Though SFCT and SF-LCVT was lower in the eyes with soft drusen compared to eyes with pachydrusen, it failed to reach statistical significance (SFCT, P = 0.1 and SF-LCVT, P = 0.06). Conclusion: The prevalence of pachydrusen in PCV and their fellow eyes is lower in Indian population suggestive of ethnic variations. SFCT and SF-LCVT was not noted to vary signifcantly in eyes with and without pachydrusen in this study cohort.


Assuntos
Doenças da Coroide/complicações , Corioide/irrigação sanguínea , Pólipos/complicações , Retina/patologia , Drusas Retinianas/epidemiologia , Acuidade Visual , Corioide/patologia , Doenças da Coroide/diagnóstico , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico , Prevalência , Drusas Retinianas/diagnóstico , Drusas Retinianas/etiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
18.
J Photochem Photobiol B ; 196: 111514, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31154277

RESUMO

Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.


Assuntos
Iodatos/toxicidade , Retina/efeitos dos fármacos , Degeneração Retiniana/patologia , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Eletrorretinografia , Ratos , Ratos Sprague-Dawley , Retina/patologia , Retina/fisiologia
19.
BMC Ophthalmol ; 19(1): 123, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151389

RESUMO

BACKGROUNDS: To assess the changes in individual retinal layer thickness and visual function associated with gains in visual acuity after an intravitreal conbercept injection in the diabetic macular edema (DME) on spectral domain optical coherence tomography (SD-OCT) and microperimetry during 1-year follow-up. METHODS: Retrospective observational study. Twenty patients with clinically significant DME in the study eye were imaged by SD-OCT every 3 months and MP1 microperimeter in the third month while receiving anti-vascular endothelial growth factor (VEGF) (conbercept) treatment. In each patient, seven retinal layers were segmented in 98 scans covering a 6 mm × 6 mm area of the macula at baseline and during 1 year of treatment. An automatic, full-threshold microperimetry of the central field (10° × 10°, 40 stimulated points) with the MP1 microperimeter. Thickness and microperimetry changes were quantitatively measured and evaluated for their correlation with increases in visual acuity. RESULTS: Although thicknesses of the inner nuclear layer (INL) and the outer nuclear layer (ONL) were reduced the most after treatment (p < 0.05), decreases of the ganglion cell layer (GCL) (r = 0.591, p = 0.006) and inner plexiform layer (IPL) (r = 0.663, p = 0.001) in central subfield area was associated with best-corrected visual acuity (BCVA) gain, and had the best estimation of BCVA gain (adjust R2 = 0.544). Mean macular sensitivity in the central subfield was also well correlated with BCVA gain (r = 0.531, p = 0.016). CONCLUSIONS: Neural recovery occurred after the resolution of edema during conbercept treatment, due to the decreases in GCL and IPL associating with gains in vision and improved microperimetry.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Retina/patologia , Acuidade Visual/fisiologia , Idoso , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Macula Lutea/fisiologia , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Estudos Retrospectivos
20.
Graefes Arch Clin Exp Ophthalmol ; 257(8): 1709-1717, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222405

RESUMO

BACKGROUND: Pigment epithelium-derived factor (PEDF)-derived 34-mer peptide (PEDF34, Asp44-Asn77) has anti-angiogenic activity but has limitations in clinical application because of an inverted bell-shaped dose-effect relationship and a short half-life. In this study, we attempted to mitigate these problems by mixing PEDF34 with type I collagen. METHODS: The anti-angiogenic activity of the PEDF34/atelocollagen mixture was evaluated by HUVEC tube formation assay and in a laser-induced choroidal neovascular (CNV) mouse model. PEDF34 and/or collagen were administrated using intravitreal injections or eye drops. CNV lesion size was quantified using FITC-dextran-perfused retinal whole mounts. Western blot analysis and inhibitor assays were used to define the action mechanisms of PEDF34 and the mixture. RESULTS: Collagen broadened the effective dose range of PEDF34 in the tube formation assay by > 250 times (from 0.2 to 50 nM). In the CNV model, five intravitreal injections of PEDF34 were required for therapeutic effect, whereas the mixture had a significant therapeutic effect following a single injection. Eye drops of the mixture showed significantly stronger CNV-suppressive effects than drops of PEDF34 alone. The anti-angiogenic activity of PEDF34 might be mediated by inhibition of ERK and JNK activation by VEGF, and collagen potentiated these effects. CONCLUSIONS: Collagen can serve as a carrier and reservoir of PEDF34. PEDF peptide/collagen mixture is easy to prepare than conventional methods for maintaining the therapeutic effect of PEDF peptide.


Assuntos
Corioide/patologia , Neovascularização de Coroide/tratamento farmacológico , Colágeno Tipo I/administração & dosagem , Proteínas do Olho/administração & dosagem , Fatores de Crescimento Neural/administração & dosagem , Serpinas/administração & dosagem , Animais , Células Cultivadas , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Lasers/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Soluções Oftálmicas , Inibidores de Proteases/administração & dosagem , Retina/patologia
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