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PURPOSE: The aim of this study was to explore the potential benefits of retinal pigment epithelium replacement therapy in patients with Bietti crystalline dystrophy (BCD) by assessing the disease pathology with the distinctive relationship between fundus autofluorescence (FAF) abnormality and visual field defect. METHODS: Sixteen eyes from 16 patients with BCD and 16 eyes from 16 patients with RHO-associated retinitis pigmentosa were included. Fundus autofluorescence, optical coherence tomography, and Goldmann perimetry results were retrospectively reviewed and assessed using image analyses. RESULTS: In patients with BCD, the FAF abnormality area was not correlated with the overall visual field defect area and median overall visual field defect area (57.5%) was smaller than FAF abnormality area (98.5%). By contrast, the ellipsoid zone width was significantly correlated with the central visual field area (r = 0.806, P < 0.001). In patients with RHO-associated retinitis pigmentosa, the FAF abnormality area and ellipsoid zone width were significantly correlated with the overall visual field defect area (r = 0.833, P < 0.001) and central visual field area (r = 0.887, P < 0.001), respectively. CONCLUSION: The FAF abnormality shown in patients with BCD involves retinal pigment epithelium degeneration without complete loss of photoreceptors or visual function. These results suggest that patients with BCD are good candidates for retinal pigment epithelium replacement therapy for preservation of residual visual function.
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Distrofias Hereditárias da Córnea , Angiofluoresceinografia , Fundo de Olho , Epitélio Pigmentado da Retina , Tomografia de Coerência Óptica , Acuidade Visual , Testes de Campo Visual , Campos Visuais , Humanos , Campos Visuais/fisiologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/fisiopatologia , Angiofluoresceinografia/métodos , Adulto , Epitélio Pigmentado da Retina/patologia , Idoso , Acuidade Visual/fisiologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/fisiopatologia , Transtornos da Visão/fisiopatologia , Transtornos da Visão/diagnóstico , Imagem Óptica , Retinose Pigmentar/fisiopatologia , Retinose Pigmentar/diagnóstico , Adulto JovemRESUMO
Given the importance of visual information to many daily activities, retinal degenerative diseases-which include both inherited conditions (such as retinitis pigmentosa) and acquired conditions (such as age-related macular degeneration)-can have a dramatic impact on human lives. The therapeutic options for these diseases remain limited. Since the discovery of the first causal gene for retinitis pigmentosa almost three decades ago, more than 250 genes have been identified, and gene therapies have been rapidly developed. Simultaneously, stem cell technologies such as induced pluripotent stem cell-based transplantation have advanced and have been applied to the treatment of retinal degenerative diseases. Here, we review recent progress in these expanding fields and discuss the potential for precision medicine in ophthalmic care.
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Terapia Baseada em Transplante de Células e Tecidos/métodos , Proteínas do Olho/genética , Terapia Genética/métodos , Degeneração Macular/terapia , Retinose Pigmentar/terapia , Transplante de Células-Tronco/métodos , Ensaios Clínicos como Assunto , Proteínas do Olho/metabolismo , Edição de Genes/métodos , Expressão Gênica , Predisposição Genética para Doença , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/transplante , Degeneração Macular/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Mutação , Optogenética/métodos , Medicina de Precisão/métodos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/transplante , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologiaRESUMO
Various advances have been made in the treatment of retinal diseases, including new treatment strategies and innovations in surgical devices. However, the treatment of degenerative retinal diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), continues to pose a significant challenge. In this review, we focus on the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to treat retinal diseases by harnessing the ability of stem cells to differentiate into different body tissues. The retina is a tissue specialized for light sensing, and its degradation leads to vision loss. As part of the central nervous system, the retina has very low regenerative capability, and therefore, treatment options are limited once it degenerates. Nevertheless, innovations in methods to induce the generation of retinal cells and tissues from ESCs/iPSCs enable the development of novel approaches for these irreversible diseases. Here we review some historical background and current clinical trials involving the use of stem-cell-derived retinal pigment epithelial cells for AMD treatment and stem cell-derived retinal cells/tissues for RP therapy. Finally, we discuss our future vision of regenerative treatment for retinal diseases with a partial focus on our studies and introduce other interesting approaches for restoring vision.
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Doenças Retinianas/terapia , Epitélio Pigmentado da Retina/citologia , Transplante de Células-Tronco , Animais , HumanosRESUMO
Currently, retinal pigment epithelium (RPE) transplantation includes sheet and single-cell transplantation, the latter of which includes cell death and may be highly immunogenic, and there are some issues to be improved in single-cell transplantation. Y-27632 is an inhibitor of Rho-associated protein kinase (ROCK), the downstream kinase of Rho. We herein investigated the effect of Y-27632 in vitro on retinal pigment epithelium derived from induced pluripotent stem cells (iPS-RPE cells), and also its effects in vivo on the transplantation of iPS-RPE cell suspensions. As a result, the addition of Y-27632 in vitro showed suppression of apoptosis, promotion of cell adhesion, and higher proliferation and pigmentation of iPS-RPE cells. Y-27632 also increased the viability of the transplant without showing obvious retinal toxicity in human iPS-RPE transplantation into monkey subretinal space in vivo. Therefore, it is possible that ROCK inhibitors can improve the engraftment of iPS-RPE cell suspensions after transplantation.
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Sobrevivência de Enxerto/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/citologia , Inibidores de Proteínas Quinases/farmacologia , Transplante de Células-Tronco , Quinases Associadas a rho/antagonistas & inibidores , Amidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Macaca fascicularis , Piridinas/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismoRESUMO
We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).
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Células-Tronco Pluripotentes Induzidas/citologia , Degeneração Macular/terapia , Epitélio Pigmentado da Retina/citologia , Idoso , Técnicas de Cultura de Células , Diferenciação Celular , Estudos de Viabilidade , Feminino , Fibroblastos , Humanos , Masculino , Epitélio Pigmentado da Retina/transplante , Transplante AutólogoRESUMO
BACKGROUND: We aimed to investigate the deformation of the outer nuclear layer using optical coherence tomography in patients with epiretinal membrane (ERM) and its relationship with metamorphopsia. METHODS: Thirty-nine eyes from 39 patients with ERM were included in the study. Patients with the subtypes of pseudo macula hole and lamellar hole were excluded. Twenty-one fellow eyes without macular disease were included as normal controls. Forty-nine B-scan images were obtained in the range of 20 degrees around the macula using SD-OCT. The outer nuclear layer (ONL) was evaluated as a three-dimensional image (3D-ONL) reconstructed using the distance between the ONL and retinal pigment epithelium (RPE) line. The deformation of the ONL was figured at the reference plane and evaluation plane (ONL-B). The characteristic parameters of the ONL-B were defined as circularity, area ratio, and axis ratio. The correlations between these parameters and visual acuity and MCHART score ratio (MH/MV) were then evaluated. RESULTS: ONL height was significantly higher in ERM patients than in normal controls (54.1 ± 5.3 µm and 84.1 ± 12.9 µm, respectively; P < 0.001). In ERM patients, the MV score was 0.53 ± 0.50, the MH score was 0.71 ± 0.61, and the distance from the RPE line to the ONL-B was 153.5 ± 13.5 µm. The axis of the ONL-B in normal controls and ERM patients was - 6.25 ± 21.8 and - 1.28 ± 29.1, respectively, which indicates that the ONL is horizontally long in both normal individuals and ERM patients. The circularity and area ratio were significantly smaller in ERM patients than in normal controls. In all ERM patients, MH/MV had a significant correlation with axis (r = - 0.29, p = 0.034), circularity (r = - 0.28, p = 0.044), and area ratio (r = - 0.47, p = 0.001). Moreover, we found that the correlation was more significant if the subjects had an axis of the ONL within ±10 degrees (n = 16); the correlations of MH/MV with axis (r = - 0.29, p = 0.034), circularity (r = - 0.53, p = 0.021), and area ratio were more significant (r = - 0.78, P < 0.0001). CONCLUSION: The ONL is horizontally long in normal individuals and ERM patients. The direction of metamorphopsia is correlated with the direction of ONL deformation.
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Membrana Epirretiniana/patologia , Retina/patologia , Transtornos da Visão/patologia , Idoso , Estudos de Casos e Controles , Membrana Epirretiniana/fisiopatologia , Feminino , Humanos , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologiaRESUMO
Retinal transplantation therapy for retinitis pigmentosa is increasingly of interest due to accumulating evidence of transplantation efficacy from animal studies and development of techniques for the differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells into retinal tissues or cells. In this study, we aimed to assess the potential clinical utility of hESC-derived retinal tissues (hESC-retina) using newly developed primate models of retinal degeneration to obtain preparatory information regarding the potential clinical utility of these hESC-retinas in transplantation therapy. hESC-retinas were first transplanted subretinally into nude rats with or without retinal degeneration to confirm their competency as a graft to mature to form highly specified outer segment structure and to integrate after transplantation. Two focal selective photoreceptor degeneration models were then developed in monkeys by subretinal injection of cobalt chloride or 577-nm optically pumped semiconductor laser photocoagulation. The utility of the developed models and a practicality of visual acuity test developed for monkeys were evaluated. Finally, feasibility of hESC-retina transplantation was assessed in the developed monkey models under practical surgical procedure and postoperational examinations. Grafted hESC-retina was observed differentiating into a range of retinal cell types, including rod and cone photoreceptors that developed structured outer nuclear layers after transplantation. Further, immunohistochemical analyses suggested the formation of host-graft synaptic connections. The findings of this study demonstrate the clinical feasibility of hESC-retina transplantation and provide the practical tools for the optimization of transplantation strategies for future clinical applications.
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Células-Tronco Embrionárias Humanas/citologia , Retina/citologia , Retina/transplante , Degeneração Retiniana/cirurgia , Animais , Diferenciação Celular , Cobalto/toxicidade , Modelos Animais de Doenças , Haplorrinos , Humanos , Células Fotorreceptoras/patologia , Primatas , Ratos , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologiaRESUMO
Retinitis pigmentosa (RP) is a group of visual impairments characterized by progressive rod photoreceptor cell loss due to a genetic background. Pigment epithelium-derived factor (PEDF) predominantly secreted by the retinal pigmented epithelium (RPE) has been reported to protect photoreceptors in retinal degeneration models, including rd1. In addition, clinical trials are currently underway outside Japan using human mesenchymal stromal cells and human neural stem cells to protect photoreceptors in RP and dry age-related macular degeneration, respectively. Thus, this study aimed to investigate the rescue effects of induced pluripotent stem (iPS)-RPE cells in comparison with those types of cells used in clinical trials on photoreceptor degeneration in rd1 mice. Cells were injected into the subretinal space of immune-suppressed 2-week-old rd1 mice. The results demonstrated that human iPS-RPE cells significantly attenuated photoreceptor degeneration on postoperative days (PODs) 14 and 21 and survived longer up to at least 12 weeks after operation than the other two types of graft cells with less immune responses and apoptosis. The mean PEDF concentration in the intraocular fluid in RPE-transplanted eyes was more than 1 µg/ml at PODs 14 and 21, and this may have contributed to the protective effect of RPE transplantation. Our findings suggest that iPS-RPE cells serve as a competent source to delay photoreceptor degeneration through stable survival in degenerating ocular environment and by releasing neuroprotective factors such as PEDF.
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Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Neurais/citologia , Fármacos Neuroprotetores/metabolismo , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/citologia , Transplante de Células-Tronco , Animais , Apoptose , Proliferação de Células , Sobrevivência de Enxerto , Humanos , Camundongos , Células Fotorreceptoras de Vertebrados/metabolismo , Degeneração Retiniana/patologiaAssuntos
Degeneração Macular , Retina , Humanos , Células-Tronco Pluripotentes Induzidas , Células-TroncoRESUMO
Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild-type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with green fluorescent protein (GFP) driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca(2 +) responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (Ih ) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When transplanted into the subretinal space of wild-type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wild-type mouse retina and exhibit Ca(2 +) responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within 2 weeks after transplantation into the retina of Crx-knockout mice and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter-driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell-replacement therapy.
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Proteínas de Homeodomínio/genética , Células Fotorreceptoras de Vertebrados/fisiologia , Retina/fisiologia , Degeneração Retiniana/terapia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/transplante , Transativadores/genética , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Cálcio/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Homeodomínio/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/fisiologia , Potenciais da Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Fotorreceptoras de Vertebrados/metabolismo , Regiões Promotoras Genéticas , Retina/metabolismo , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Degeneração Retiniana/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Transplante de Células-Tronco , Transativadores/metabolismoRESUMO
This study evaluates the transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into patients with advanced retinitis pigmentosa using adaptive optics optical coherence tomography (AO-OCT) to monitor retinal changes over two years post transplantation. Our results confirmed successful engraftment and increased retinal thickness, with AO-OCT providing detailed visualization of cellular structures such as an outer plexiform layer-like line and highly reflective particles within rosette-like formations, indicative of photoreceptor development. Immunohistological analysis in a parallel monkey model confirmed these structures as mature, functional photoreceptor rosettes. The integration of high-resolution AO-OCT with immunohistology provides critical insights into the structural and functional outcomes of transplantation and represents a promising advancement in the treatment of retinal degenerative diseases.
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Pluripotent stem cell-based therapy for retinal degenerative diseases is a promising approach to restoring visual function. A clinical study using retinal organoid (RO) sheets was recently conducted in patients with retinitis pigmentosa. However, the graft preparation currently requires advanced skills to identify and excise suitable segments from the transplantable area of the limited number of suitable ROs. This remains a challenge for consistent clinical implementations. Herein, we enabled the enrichment of wild-type (non-reporter) retinal progenitor cells (RPCs) from dissociated ROs using a label-free ghost cytometry (LF-GC)-based sorting system, where a machine-based classifier was trained in advance with another RPC reporter line. The sorted cells reproducibly formed retinal spheroids large enough for transplantation and developed mature photoreceptors in the retinal degeneration rats. This method of enriching early RPCs with no specific surface antigens and without any reporters or chemical labeling is promising for robust preparation of graft tissues during cell-based therapy.
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Células-Tronco Pluripotentes , Degeneração Retiniana , Retinose Pigmentar , Humanos , Animais , Ratos , Espécies Reativas de Oxigênio , Retina , Células-Tronco Pluripotentes/transplante , Degeneração Retiniana/terapia , Retinose Pigmentar/terapia , Transplante de Células-Tronco/métodosRESUMO
Introduction: The retinal pigment epithelium (RPE) plays essential roles in maintaining retinal functions as well as choroidal capillaries and can lead to visual disorders if dysfunctional. Transplantation of human-induced pluripotent stem cell-derived RPE (hiPSC-RPE) is a promising therapy for such RPE impaired conditions including age-related macular degeneration. The challenge with cell suspension transplantation is targeted delivery of graft cells and undesired cell reflux. Gelatin hydrolysate, a soluble variant with specific molecular weight distribution, is examined in this study for its potential use in hiPSC-RPE suspension transplantation, particularly in reducing cell reflux and enhancing RPE engraftment. Methods: A retinal bleb model was created using polydimethylsiloxane (PDMS) soft lithography to quantify cellular reflux. We examined the effects of gelatin hydrolysate on the hiPSC-RPE of various aspects of cell behavior and performance such as cell viability, hypoxia reaction, morphology, induction of inflammation and immune responses. Results: Gelatin hydrolysate at 5 % concentration effectively mitigated cell reflux in vitro mimic, improved cell viability, reduced cell aggregation, and had an inhibitory effect on hypoxic reactions due to cell deposition with hiPSC-RPE. Additionally, gelatin hydrolysate did not affect cell adhesion and morphology, and decreased the expression of major histocompatibility complex class II molecules, which suggests reduced immunogenicity of hiPSC-RPE. Conclusion: Gelatin hydrolysate is considered a valuable and useful candidate for future regenerative therapies in hiPSC-RPE suspension transplantation.
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This study aimed to investigate how the extent and central/peripheral location of the residual visual field (VF) in patients with late-stage inherited retinal diseases (IRDs) are related to retinal sensitivity detected using full-field stimulus testing (FST). We reviewed the results of Goldmann perimetry and FST from the medical records of patients with IRDs whose VF represents central (within 10°) and/or peripheral islands, or undetectable. In total, 19 patients (19 eyes) were analyzed in this study. The median value of residual VF area was 1.38%. The median values of rod and cone sensitivities were - 14.9 dB and 7.4 dB, respectively. Patients with only the peripheral island (- 33.9 dB) had better median rod sensitivity than other groups (only central, - 18.9 dB; both, - 3.6 dB). VF area significantly correlated with rod sensitivity (r = - 0.943, p = 0.005) in patients with only peripheral island, but not with cone sensitivity. Peripheral VF islands were significant contributors to FST results, especially rod sensitivity. With reduced or loss of central vision, the extent of residual peripheral VF significantly affected rod sensitivity, suggesting that FST can be useful in quantitatively estimating the overall remaining vision in patients with late-stage IRD.
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Degeneração Retiniana , Campos Visuais , Humanos , Testes de Campo Visual/métodos , Adaptação à Escuridão , RetinaRESUMO
Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.
Assuntos
Células-Tronco Pluripotentes Induzidas , Macaca fascicularis , Epitélio Pigmentado da Retina , Animais , Epitélio Pigmentado da Retina/transplante , Epitélio Pigmentado da Retina/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Degeneração Macular/patologiaRESUMO
PURPOSE: To evaluate whether the status of the external limiting membrane (ELM) or inner segment/outer segment junction (IS/OS) improves after intravitreal injection of ranibizumab for age-related macular degeneration (AMD). We also evaluated whether the pre-operative values of these parameters are associated with the visual prognosis. METHODS: This was a hospital-based, cross-sectional study. Seventy-six eyes of 76 treatment-naive AMD patients who received three monthly intravitreal injections of ranibizumab followed for more than 6 months with additional as-needed injections were investigated. Spectral domain OCT was used to evaluate the length of ELM, IS/OS, and foveal thickness pre- and post-operatively. Changes of ELM and IS/OS length were evaluated postoperatively. Correlation coefficients between pre-operative parameters and post-operative visual acuity were also analyzed. RESULTS: Significant changes were noted in mean logMAR (0.66 to 0.53), foveal thickness (231.1 to 151.1 µm), and IS/OS length (514.9 to 832.3 µm) after the treatment. ELM length did not improve significantly (1,312.4 to 1,376.7 µm). Restoration of IS/OS occurred where ELM is retained. Although pre-operative ELM length, IS/OS length, and foveal thickness showed correlation with post-operative logMAR (R = -0.51, -0.39, and 0.46, respectively), the most powerful predictive factor for visual prognosis was pre-operative logMAR (R = 0.77, p < 0.001). CONCLUSIONS: IS/OS status improves in response to anti-VEGF therapy but ELM seems to have less plasticity. The status of IS/OS and ELM can be used as prognostic factors but the predictive power is inferior to that of baseline visual acuity.
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Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Degeneração Macular/tratamento farmacológico , Segmento Interno das Células Fotorreceptoras da Retina/fisiologia , Segmento Externo das Células Fotorreceptoras da Retina/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Idoso , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Membrana Basal , Corantes , Estudos Transversais , Membrana Epirretiniana/fisiopatologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Verde de Indocianina , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Masculino , Variações Dependentes do Observador , Ranibizumab , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To investigate when and how fast the foveal thinning occurs in central serous chorioretinopathy. METHODS: Outer nuclear layer (ONL) thickness was measured in 60 eyes of 60 patients with active central serous chorioretinopathy. Patients were divided into 3 groups based on the duration of symptoms; within 1 month (Group A, 25 eyes), 1 to 6 months (Group B, 17 eyes), and >6 months (Group C, 18 eyes). Outer nuclear layer thickness and visual acuity were compared between each group. Some of the patients underwent several examinations and serial changes were analyzed. RESULTS: The ONL thickness was correlated with the duration of symptoms (R = -0.61, P < 0.001). Visual acuity was worse in Group C compared with Group A (P = 0.003). The mean ONL thickness of each group and healthy contralateral eyes was 82.4, 70.2, 53.5, and 89.3 µm, respectively. Comparisons between each group showed statistical significances. Seventeen eyes in Group A were re-examined between 3 and 6 months after the first visit. The mean ONL thickness significantly decreased from 81.9 µm to 75.0 µm (P = 0.020). CONCLUSION: In central serous chorioretinopathy, ONL thinning starts in the early stage and may continue as long as the subretinal fluid persists.
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Coriorretinopatia Serosa Central/fisiopatologia , Fóvea Central/patologia , Descolamento Retiniano/fisiopatologia , Adulto , Idoso , Coriorretinopatia Serosa Central/diagnóstico , Corantes , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Líquido Sub-Retiniano , Fatores de Tempo , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
In recent decades, many researchers have attempted to restore vision via transplantation of retina/retinal cells in eyes with retinal degeneration. The advent of induced pluripotent stem cells (iPSC) and retinal organoid induction technologies has boosted research on retinal regeneration therapy. Although the recognition of functional integration of graft photoreceptor cells in the host retina from 2006 has been disputed a decade later by the newly evidenced phenomenon denoted as "material transfer," several reports support possible reconstruction of the host-graft network in the retinas of both end-stage degeneration and in progressing degeneration cases. Based on proof of concept (POC) studies in animal models, a clinical study was conducted in Kobe, Japan in 2020 and showed the feasibility of cell-based therapy using iPSC retinal organoid technology. Although the graft potency of human embryonic stem (ES)/iPS cell-derived retinal organoid/retinal cells has been suggested by previous studies, much is still unknown regarding host capability, that is, how long-standing human degenerating retinas are capable of rewiring with transplanted cells. This review summarizes past POC studies on photoreceptor replacement therapy and introduces some new challenges to maximize the possible efficacy in future human clinical studies of regenerative therapy.
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The discovery of induced Pluripotent Stem) (iPS) cells has instigated innovation in various fields, including ophthalmology. Cell therapy has shown tremendous progress in translational research on retinal diseases, including the first-in-human transplantation of autologous iPS cell-derived retinal pigment epithelium (RPE) cells for patients with age-related macular degeneration (AMD). Cell therapy for retinitis pigmentosa (RP) has also been developed. Retinal organoid and photoreceptor cell transplantation has been shown to incorporate into the degenerated host retina, forming synapses with host neurons and resulting in functional recovery. Based on preclinical data, first-in-human transplantation of iPS cell-derived retinal sheets has been conducted. In this review, we summarize the current progress in iPS cell-based retinal cell transplantation research for retinal diseases, addressing some remaining challenges and future prospects.
Assuntos
Células-Tronco Pluripotentes Induzidas , Degeneração Retiniana , Doenças Retinianas , Humanos , Doenças Retinianas/cirurgia , Retina , Epitélio Pigmentado da Retina , Terapia Baseada em Transplante de Células e Tecidos , Transplante de CélulasRESUMO
Purpose: Novel therapeutic options, such as regenerative medicine and gene therapy, are now emerging as viable treatment options for patients with severe visual impairments, such as retinitis pigmentosa (RP). Gradable assessment of patients' visual function is essential to consider treatment options and to evaluate treatment outcomes; however, evaluation of visual function in patients with advanced low vision is often challenging because of patients' poor and sometimes unpredictable responses. In this study, we attempted to accurately assess visual capabilities and disease stage in patients with RP with a visual acuity (VA) of ≤ 0.01. Design: Retrospective analysis of visual function indicators, including VA, retinal thickness, full-field stimulus testing (FST), and chromatic pupillometry. Subjects: Overall, 43 patients (84 eyes) with advanced RP with a VA of ≤ 0.01 visited Kobe City Eye Hospital from 2019 to 2021. Methods: Hierarchical (multilevel) Bayesian modeling was used to estimate individual eye's pupil response and FST threshold, taking into account the ambiguity and randomness often observed in patients with ultralow vision. Using the estimated ability obtained from each test, the correlation between each test and retinal thickness was further analyzed to make a comprehensive assessment of the data. Main Outcome Measures: Visual acuity, retinal thickness, FST threshold, and pupil diameter change to different light stimuli. Results: Full-field stimulus testing and pupillometry measurements were moderately correlated with VA but exhibited a wide range of values within the same VA groups. Full-field stimulus testing was not correlated with central retinal thickness at counting fingers/hand motion VA range and seemed to reflect overall remaining photoreceptor function, including peripheral retina. Pupillometry may be able to distinguish between different levels of inner retinal function. Conclusions: The combination of pupillometry and FST allowed for graded evaluation of visual function within patients grouped in the same VA groups in patients with advanced RP with ultralow vision. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.