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1.
Artigo em Inglês | MEDLINE | ID: mdl-39390122

RESUMO

PURPOSE: To investigate the effect of internal limiting membrane (ILM) peeling on visual outcomes and postoperative epiretinal membrane (ERM) after pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) associated with retinal vein occlusion (RVO) with various degrees of macular ischemia. METHODS: We compared the outcomes of eyes that underwent vitrectomy with and without ILM peeling from 2012 to 2021 with a minimum follow-up of 6 months. RESULTS: 112 charts were analyzed, and 51 eyes met the inclusion criteria. There were 19 eyes with ILM peeling and 32 eyes with non-ILM peeling. Baseline characteristics did not differ significantly. The mean postoperative visual acuity significantly improved at 6 months compared with the mean preoperative visual acuity (P < 0.001). Visual improvement was significantly greater in the non-ILM peeling group(P < 0.05). Without ischemia within the arcade, there was no significant difference in the visual improvement. In patients with ischemia, the visual improvement in the ILM peeling group was significantly worse than that in the non-ILM peeling group. The incidence of postoperative ERM was significantly higher in the non-ILM peeling; however, there was no significant change in postoperative vision due to the presence of ERM. CONCLUSIONS: Vitrectomy either with or without ILM peeling results in visual improvement in patients with VH associated with RVO; however, it should be uniformly avoiding ILM peeling in cases with pre-existing macular ischemia, as it may significantly lead to a deterioration in visual outcomes. KEY MESSAGES: What is known Pars plana vitrectomy is effective for visual improvement in vitreous hemorrhage associated with retinal vein occlusion. The incidence of postoperative epiretinal membrane is variable depending on the surgical approach. What is new Avoiding ILM peeling in cases of macular ischemia during vitrectomy is crucial for better visual outcomes. Despite higher rates of epiretinal membrane post-surgery in non-ILM peeled eyes, their visual outcomes remain superior to those with ILM peeling.

2.
BMC Ophthalmol ; 24(1): 299, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033302

RESUMO

BACKGROUND: In severe Proliferative Diabetic Retinopathy (PDR), fibrovascular membrane (FVM) causes macular tractional retinal detachment (MTRD) which threatens vision and eventually leads to blindness. Here we present a case of separation between the inner and outer retina in tractional retinoschisis, induced during intraoperative FVM delamination. CASE PRESENTATION: A 68-year-old woman presented with PDR in the right eye, characterized by a combined FVM and retinal detachment, for which a vitrectomy was performed. Multiple holes, large retinal detachment extending to all quadrants, and white-lined blood vessels with FVM were found during the procedure. When membrane delamination was performed, it strayed into the space between the inner and outer retinal layers without being noticed due to retinoschisis and multiple retinal holes. After removing the FVM and detaching the separated inner retina, fluid-gas and photocoagulation were performed. Retinal reattachment was successfully achieved after surgery, and the postoperative visual acuity was improved and maintained for 26 months postoperatively. CONCLUSIONS: When tractional retinoschisis due to FVM is combined with retinal holes in tractional retinal detachment (TRD), care must be taken to prevent delamination from straying into retinoschisis during separation.


Assuntos
Retinopatia Diabética , Descolamento Retiniano , Retinosquise , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Feminino , Idoso , Retinosquise/cirurgia , Retinosquise/etiologia , Retinosquise/diagnóstico , Retinopatia Diabética/cirurgia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Vitrectomia/métodos , Acuidade Visual/fisiologia , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Descolamento Retiniano/diagnóstico , Perfurações Retinianas/cirurgia , Perfurações Retinianas/etiologia , Perfurações Retinianas/diagnóstico , Complicações Intraoperatórias
3.
Endocr J ; 71(10): 965-971, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38925989

RESUMO

We previously reported that a high HbA1c level 3 months before vitrectomy for vitreous hemorrhage or a large preoperative decrease in the HbA1c level over 3 months tended to increase the risk of rebleeding in diabetic retinopathy patients evaluated between 2010 and 2014. Here, we aimed to confirm these results with an extended study period and an increased number of operated eyes. This study included 121 diabetic patients who were admitted to Osaka University Hospital between 2010 and 2019 and who underwent vitrectomy for vitreous hemorrhage. Binomial logistic regression analysis was performed with the presence of postoperative bleeding as the outcome. The present study showed that the duration of the operation was associated with rebleeding (odds ratio = 1.02, p = 0.0016). A high HbA1c level just before vitrectomy tended to be associated with the bleeding (odds ratio = 1.27, p = 0.05), while preoperative HbA1c changes were not associated with rebleeding. The results of this study suggest that a high preoperative HbA1c level just before vitrectomy, not a decrease in HbA1c levels, in addition to the duration of the operation may increase the risk of postoperative bleeding after vitrectomy in diabetic retinopathy patients.


Assuntos
Retinopatia Diabética , Hemoglobinas Glicadas , Hemorragia Pós-Operatória , Vitrectomia , Hemorragia Vítrea , Humanos , Retinopatia Diabética/cirurgia , Retinopatia Diabética/sangue , Vitrectomia/efeitos adversos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hemorragia Vítrea/cirurgia , Hemorragia Vítrea/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/etiologia , Idoso , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco
4.
Graefes Arch Clin Exp Ophthalmol ; 261(6): 1545-1552, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36473986

RESUMO

PURPOSE: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months. RESULTS: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R2 = 0.171, P = 0.056) and a greater displacement of SMH (R2 = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001). CONCLUSIONS: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.


Assuntos
Inibidores da Angiogênese , Pólipos , Humanos , Vasculopatia Polipoidal da Coroide , Estudos Retrospectivos , Resultado do Tratamento , Injeções Intravítreas , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/tratamento farmacológico , Hemorragia Retiniana/etiologia , Corioide , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica , Pólipos/complicações , Pólipos/diagnóstico , Pólipos/tratamento farmacológico
5.
BMC Ophthalmol ; 22(1): 198, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501767

RESUMO

BACKGROUND: This study aimed to evaluate macular vessel tortuosity using optical coherence tomography angiography (OCTA) and its association with visual outcomes in eyes undergoing surgery for epiretinal membrane (ERM). METHODS: The study included 22 consecutive patients who underwent vitrectomy for ERM between May 2019 and July 2020 and OCTA at Osaka University Hospital. All patients underwent ophthalmologic examinations, including swept-source OCTA. Standard vitrectomy was performed, and the patients were followed up for 6 months postoperatively. Distortion of retinal vessels was calculated using two parameters: the actual vessel length in the vessel section (VL) and the direct vessel branching point distance (BD) in the three quadrants (nasal, temporal, and superior-inferior) of the macula. We analyzed the correlation between these parameters and visual outcomes. RESULTS: Significantly longer VL was found at 1, 3, and 6 months postoperatively (p = 0.006, 0.008, and 0.022, respectively) in the temporal quadrant compared to baseline temporal VL. Significantly shorter VL was found in nasal quadrants at 1 and 3 months (p = 0.046 and p = 0.018) in the comparison of nasal baseline VL. VL/BDs were correlated with the same postoperative best-corrected visual acuity (BCVA) at 1, 3, and 6 months (p = 0.035, 0.035, and 0.042, respectively) in the superior-inferior quadrant. A significant association of changes in VL and BCVA was found at 3 and 6 months postoperatively in the nasal quadrant (p = 0.018 and 0.0455, respectively). CONCLUSIONS: Changes in vascular distortion after ERM surgery can be measured using OCTA. The change in vessels around the macula became more linear; this was associated with visual outcomes after surgery.


Assuntos
Membrana Epirretiniana , Macula Lutea , Angiografia , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Humanos , Tomografia de Coerência Óptica/métodos , Acuidade Visual
6.
Graefes Arch Clin Exp Ophthalmol ; 259(10): 2897-2903, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33861366

RESUMO

PURPOSE: To examine the associations between the disorganization of the retinal inner layers (DRIL) and optical coherence tomography angiography characteristics and visual acuity (VA) outcomes in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: In this single-center cross-sectional cohort study, the data of 43 patients with macular edema secondary to BRVO that received pro re nata anti-vascular endothelial growth factor therapy were analyzed. B-scan and en face angiographic images were obtained by swept-source-based wide-field optical coherence tomography angiography performed at a single visit 1 month after the anti-vascular endothelial growth factor therapy session and evaluated. Correlations between the vascular indices in macula-centered 3 × 3 and 12 × 12 mm2 areas and B-scan parameters, such as DRIL length and VA, were examined. RESULTS: The mean DRIL length (Rs = 0.588, p < 0.001) and the proportion of scans with DRIL out of five scans (Rs = 0.507, p = 0.001) were significantly correlated with the final best-corrected VA in patients with BRVO. DRIL length was associated with vascular density (VD) and vascular length in the macula (Rs = - 0.425, p = 0.006 and Rs = - 0.382, p = 0.013, respectively), but not with VD and vascular length in the larger areas (12 × 12 mm2). Multilinear regression analysis revealed that the extent of macular edema (p = 0.0016) and VD in the 3 × 3 mm2 area (p = 0.004) was significantly associated with the DRIL development. CONCLUSION: DRIL severity was correlated with VA and associated with the peri-macular perfusion status in eyes with BRVO. Macular edema and macular perfusion affected DRIL severity. These findings would help understand the pathogenesis of DRIL in eyes with BRVO.


Assuntos
Oclusão da Veia Retiniana , Estudos Transversais , Angiofluoresceinografia , Seguimentos , Humanos , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica
7.
Graefes Arch Clin Exp Ophthalmol ; 259(9): 2615-2624, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33687562

RESUMO

PURPOSE: To compare the choroidal neovascularization (CNV) flow patterns and the relationship between perforating vessels (PVs) and CNV in the three different stages of networks in myopic CNV (mCNV) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This retrospective study included 28 eyes with mCNV that was divided into three phases (active, scar, and atrophic) and observed by SS-OCTA. SS-OCTA findings, with special focus on the relationship between the PVs and CNV, were compared among the three phases. RESULTS: Overall, the CNV signal was detected in 31 of the 34 areas of CNV (91%); in the active, scar, and atrophic phases, respectively, CNV signals were detected in eight of eight areas of CNV (100%), 10 of 11 areas of CNV (91%), and 13 of 15 areas of CNV (86%). Two signal patterns were observed in each phase, i.e., dense and loop; in the atrophic phase, seven eyes were unclassifiable. The ratio between the dense and loop patterns did not differ significantly among the phases. In 30 of 34 areas of CNV for which clear images were obtained, the PVs and CNV were connected directly or indirectly in 19 area of CNV, and in five areas of CNV, trunk-like vessels were connected to the PVs within the CNV. The numbers of foveal or parafoveal CNVs accompanied by PVs were significantly (p=0.0048) greater than those of the extrafoveal CNV. CONCLUSIONS: OCTA provides detailed observation of mCNV and the relationship between CNV and PVs. Although the CNV signal pattern does not differ depending on the degree of atrophy, there are cases in which only the trunk-like vessels connect to the PVs within the CNV in the atrophic phase without CNV flow signal.


Assuntos
Neovascularização de Coroide , Corioide , Neovascularização de Coroide/diagnóstico , Angiofluoresceinografia , Fundo de Olho , Humanos , Estudos Retrospectivos , Tomografia de Coerência Óptica
8.
Graefes Arch Clin Exp Ophthalmol ; 259(10): 2919-2927, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33893866

RESUMO

PURPOSE: Our previous 1-year pilot study evaluated the efficacy of intravitreally injected activated protein C (APC) in 10 eyes with ischemic central retinal vein occlusion (CRVO). The reperfusion of the areas of retinal nonperfusion (RNP) exceeded 50% of the baseline in five (50%) eyes 1 year after the APC injection. The current study evaluated the long-term efficacy and safety of intravitreal APC. METHODS: The 10 eyes in the pilot study were included in this study. Other treatments were administered at the physicians' discretion after the pilot study. We evaluated visual acuity (VA), central retinal thickness (CRT) and perfusion status, and adverse events and severity over the long term. RESULTS: The median follow-up was 60 months (range, 48-68 months). Compared with baseline, the post-treatment VA improved significantly (P < 0.001) from 1.39 to 1.06 logarithm of the minimum angle of resolution. The CRT improved significantly (P < 0.001) from 1090 to 195 µm at the last visit. The RNP areas decreased from an average 29.7 disc areas (DAs) at baseline to an average 16.5 DAs at the last examination (mean, 40 ± 6.5 months after the first APC treatment). No adverse events were related to intravitreal APC. CONCLUSION: No complications were associated with intravitreal APC, the clinical course improved, and improved RNP was maintained for the long term, suggesting that intravitreal APC may be an alternative treatment for CRVO.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Inibidores da Angiogênese/uso terapêutico , Seguimentos , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Projetos Piloto , Proteína C/uso terapêutico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica , Resultado do Tratamento
9.
BMC Ophthalmol ; 21(1): 200, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962561

RESUMO

BACKGROUND: During panretinal photocoagulation (PRP), the outer retina, especially the photoreceptors, are destroyed. During such procedures, the impact of the retinal photocoagulation, which is performed in the same photocoagulated area, may change if it is applied to different locations with different photoreceptor densities. Thus, we aimed to evaluate the influence of photoreceptor density on PRP. METHODS: We constructed a three-dimensional (3D) average distribution of photoreceptors with 3D computer-aided design (CAD) software using previously derived photoreceptor density data and calculated the number of photoreceptors destroyed by scatter PRP and full-scatter PRP (size 400-µm on the retina, spacing 1.0 spot) using a geometry-based simulation. To investigate the impact of photoreceptor density on PRP, we calculated the ratio of the number of photoreceptors destroyed to the total number of photoreceptors, termed the photoreceptor destruction index. RESULTS: In this 3D simulation, the total number of photoreceptors was 96,571,900. The total number of photoreceptors destroyed by scatter PRP and full-scatter PRP were 15,608,200 and 19,120,600, respectively, and the respective photoreceptor destruction indexes were 16.2 and 19.8%, respectively. CONCLUSIONS: Scatter PRP is expected to have 4/5 of the number of photoreceptors destroyed by full-scatter PRP.


Assuntos
Retinopatia Diabética , Corioide , Retinopatia Diabética/cirurgia , Humanos , Fotocoagulação a Laser , Lasers , Retina/diagnóstico por imagem , Retina/cirurgia
10.
Glia ; 67(2): 332-344, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484883

RESUMO

Ischemia-induced angiogenesis contributes to various neuronal and retinal diseases, and often results in neurodegeneration and visual impairment. Current treatments involve the use of anti-VEGF agents but are not successful in all cases. In this study we determined that miR-30a-5p is another important mediator of retinal angiogenesis. Using a rodent model of ischemic retinopathy, we show that inhibiting miR-30a-5p reduces neovascularization and promotes tissue repair, through modulation of microglial and endothelial cell cross-talk. miR-30a-5p inhibition results in increased expression of the death receptor Fas and CCL2, to decrease endothelial cell survival and promote microglial migration and phagocytic function in focal regions of ischemic injury. Our data suggest that miR-30a-5p inhibition accelerates tissue repair by enhancing FasL-Fas crosstalk between microglia and endothelial cells, to promote endothelial cell apoptosis and removal of dead endothelial cells. Finally, we found that miR-30a levels were increased in the vitreous of patients with proliferative diabetic retinopathy. Our study identifies a role for miR-30a in the pathogenesis of neovascular retinal disease by modulating microglial and endothelial cell function, and suggests it may be a therapeutic target to treat ischemia-mediated conditions.


Assuntos
Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Microglia/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/fisiologia , Receptor fas/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Lectinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Neovascularização Patológica/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Interferência de RNA/fisiologia , RNA Mensageiro/metabolismo
11.
Graefes Arch Clin Exp Ophthalmol ; 257(1): 161-167, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30374615

RESUMO

PURPOSE: To evaluate the capability of anterior segment Scheimpflug imaging for detecting primary angle closure disease (PACD): primary angle closure suspect, primary angle closure, and primary angle closure glaucoma, using cutoff points derived from reference databases of healthy subjects. METHODS: Eighty-seven patients with PACD and 49 age-matched control subjects were included. We evaluated the sensitivity and specificity of anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) to differentiate patients with PACD from controls. Additionally, the study's raw data was analyzed via receiver operating characteristic curves for comparison. RESULTS: One standard deviation from the normative data's mean values was used as the cutoff point and yielded a sensitivity and specificity of 96.2% and 92.6% for ACD, 97.1% and 75.9% for ACV, and 93.3% and 72.2% for ACA, respectively. Receiver operating characteristic analysis of the raw data showed the area under the curve to be 0.984, 0.975, and 0.931 for ACD, ACV, and ACA, respectively. CONCLUSIONS: Our study demonstrated that the parameters of anterior segment Scheimpflug imaging, particularly ACD, accurately discriminate PACD. This was the first study to validate the device's normative data in a separate population. With its high reproducibility, ease of use, non-invasiveness, and speed, anterior segment Scheimpflug imaging is a potentially powerful screening tool for PACD.


Assuntos
Câmara Anterior/diagnóstico por imagem , Glaucoma de Ângulo Fechado/diagnóstico , Gonioscopia/métodos , Pressão Intraocular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos
12.
Circulation ; 136(2): 180-195, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28356444

RESUMO

BACKGROUND: Anti-angiogenic biologicals represent an important concept for the treatment of vasoproliferative diseases. However, the need for continued treatment, the presence of nonresponders, and the risk of long-term side effects limit the success of existing therapeutic agents. Although Tspan12 has been shown to regulate retinal vascular development, nothing is known about its involvement in neovascular disease and its potential as a novel therapeutic target for the treatment of vasoproliferative diseases. METHODS: Rodent models of retinal neovascular disease, including the mouse model of oxygen-induced retinopathy and the very low density lipoprotein receptor knockout mouse model were analyzed for Tspan/ß-catenin regulation. Screening of a phage display of a human combinatorial antibody (Ab) library was used for the development of a high-affinity Ab against Tspan12. Therapeutic effects of the newly developed Ab on vascular endothelial cells were tested in vitro and in vivo in the oxygen-induced retinopathy and very low density lipoprotein receptor knockout mouse model. RESULTS: The newly developed anti-Tspan12 Ab exhibited potent inhibitory effects on endothelial cell migration and tube formation. Mechanistic studies confirmed that the Ab inhibited the interaction between Tspan12 and Frizzled-4 and effectively modulates ß-catenin levels and target genes in vascular endothelial cells. Tspan12/ß-catenin signaling was activated in response to acute and chronic stress in the oxygen-induced retinopathy and very low density lipoprotein receptor mouse model of proliferative retinopathy. Intravitreal application of the Ab showed significant therapeutic effects in both models without inducing negative side effects on retina function. Moreover, combined intravitreal injection of the Ab with a known vascular endothelial growth factor inhibitor, Aflibercept, resulted in significant enhancement of the therapeutic efficacy of each monotherapy. Combination therapy with the Tspan12 blocking antibody can be used to reduce anti-vascular endothelial growth factor doses, thus decreasing the risk of long-term off-target effects. CONCLUSIONS: Tspan12/ß-catenin signaling is critical for the progression of vasoproliferative disease. The newly developed anti-Tspan12 antibody has therapeutic effects in vasoproliferative retinopathy and can enhance the potency of existing anti- vascular endothelial growth factor agents.


Assuntos
Neovascularização Retiniana/metabolismo , Transdução de Sinais/fisiologia , Tetraspaninas/antagonistas & inibidores , Tetraspaninas/metabolismo , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos/genética , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Injeções Intravítreas , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neovascularização Retiniana/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
13.
EMBO J ; 31(4): 842-55, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22179698

RESUMO

Vasculogenesis, the in-situ assembly of angioblast or endothelial progenitor cells (EPCs), may persist into adult life, contributing to new blood vessel formation. However, EPCs are scattered throughout newly developed blood vessels and cannot be solely responsible for vascularization. Here, we identify an endothelial progenitor/stem-like population located at the inner surface of preexisting blood vessels using the Hoechst method in which stem cell populations are identified as side populations. This population is dormant in the steady state but possesses colony-forming ability, produces large numbers of endothelial cells (ECs) and when transplanted into ischaemic lesions, restores blood flow completely and reconstitutes de-novo long-term surviving blood vessels. Moreover, although surface markers of this population are very similar to conventional ECs, and they reside in the capillary endothelium sub-population, the gene expression profile is completely different. Our results suggest that this heterogeneity of stem-like ECs will lead to the identification of new targets for vascular regeneration therapy.


Assuntos
Vasos Sanguíneos/citologia , Endotélio Vascular/citologia , Células-Tronco/citologia , Animais , Vasos Sanguíneos/metabolismo , Endotélio Vascular/metabolismo , Perfilação da Expressão Gênica , Humanos , Recém-Nascido , Camundongos , Neovascularização Patológica , Células-Tronco/metabolismo
14.
Development ; 139(7): 1327-35, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22357924

RESUMO

Interactions between astrocytes and endothelial cells (ECs) are crucial for retinal vascular formation. Astrocytes induce migration and proliferation of ECs via their production of vascular endothelial growth factor (VEGF) and, conversely, ECs induce maturation of astrocytes possibly by the secretion of leukemia inhibitory factor (LIF). Together with the maturation of astrocytes, this finalizes angiogenesis. Thus far, the mechanisms triggering LIF production in ECs are unclear. Here we show that apelin, a ligand for the endothelial receptor APJ, induces maturation of astrocytes mediated by the production of LIF from ECs. APJ (Aplnr)- and Apln-deficient mice show delayed angiogenesis; however, aberrant overgrowth of endothelial networks with immature astrocyte overgrowth was induced. When ECs were stimulated with apelin, LIF expression was upregulated and intraocular injection of LIF into APJ-deficient mice suppressed EC and astrocyte overgrowth. These data suggest an involvement of apelin/APJ in the maturation process of retinal angiogenesis.


Assuntos
Astrócitos/citologia , Células Endoteliais/citologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adipocinas , Animais , Apelina , Receptores de Apelina , Proliferação de Células , Células Endoteliais/metabolismo , Humanos , Fator Inibidor de Leucemia/metabolismo , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica , Retina/patologia
15.
J Biol Chem ; 288(18): 12469-77, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23504320

RESUMO

Tie2 is a receptor tyrosine kinase expressed on vascular endothelial cells (ECs). It has dual roles in promoting angiogenesis and stabilizing blood vessels, and it has been suggested that Tie2 forms dimers and/or oligomers in the absence of angiopoietin-1 (Ang1); however, the mechanism of ligand-independent dimerization of Tie2 and its biological significance have not been clarified. Using a bimolecular fluorescence complementation assay and a kinase-inactive Tie2 mutant, we show here that ligand-independent Tie2 dimerization is induced without Tie2 phosphorylation. Moreover, based on the fact that Tie1 never forms heterodimers with Tie2 in the absence of Ang1 despite having high amino acid sequence homology with Tie2, we searched for ligand-independent dimerization domains of Tie2 by reference to the difference with Tie1. We found that the YIA sequence of the intracellular domain of Tie2 corresponding to the LAS sequence in Tie1 is essential for this dimerization. When the YIA sequence was replaced by LAS in Tie2 (Tie2YIA/LAS), ligand-independent dimer was not formed in the absence of Ang1. When activation of Tie2YIA/LAS was induced by a high dose of Ang1, phosphorylation of Tie2 was limited compared with wild-type Tie2, resulting in retardation of activation of Erk downstream of Tie2. Therefore, these data suggest that ligand-independent dimerization of Tie2 is essential for a strong response upon stimulation with high dose Ang1.


Assuntos
Angiopoietina-1/farmacologia , Multimerização Proteica/efeitos dos fármacos , Receptor TIE-2/metabolismo , Motivos de Aminoácidos , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Animais , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , Humanos , Camundongos , Células NIH 3T3 , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Estrutura Terciária de Proteína , Receptor de TIE-1/genética , Receptor de TIE-1/metabolismo , Receptor TIE-2/genética
16.
Am J Ophthalmol Case Rep ; 34: 102017, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38404483

RESUMO

Purpose: While secondary epiretinal membranes (ERMs) are well-documented postoperative complications following rhegmatogenous retinal detachment (RRD) surgery, literature addressing the mechanisms of spontaneous resolution, particularly in cases involving vitrectomy, remain limited. In this case report, we describe the spontaneous resolution of secondary ERM in an amateur boxer following traumatic RRD surgery. Observations: Pars plana vitrectomy was performed for traumatic RRD in a 20-year-old man. Secondary ERM formation was observed one month after RRD surgery, resulting in retinal distortion. The ERM began to peel spontaneously and disappeared one year after surgery. His visual function did not deteriorate in the meantime. Conclusions and Importance: Spontaneous ERM separation is possible even after vitrectomy. This is the first published observation of the formation and spontaneous disappearance of secondary ERM after vitrectomy without intervention.

17.
Am J Ophthalmol Case Rep ; 32: 101894, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37609516

RESUMO

Purpose: We present a case of traumatic commotio retinae (CR), in which blood flow was evaluated using optical coherence tomography angiography (OCTA). Observations: An 18-year-old Japanese man presented with traumatic retinal detachment and CR in his left eye, which had been hit by a handball. Fundus examination revealed peripheral retinal tear extending from the 1 to 3 o'clock position with retinal detachment, and CR near the area of tear. Fluorescein angiography (FA) confirmed an ischemic area near the retinal tear area at the CR. The patient underwent successful scleral buckling and cryopexy. Sequential OCTA imaging was performed and we were able to determine perfusion in the CR area, with maintained blood flow. Conclusions and importance: In blunt eye trauma, peripheral commotio retinae can be assessed non-invasively over time using OCTA. OCTA is a useful method for evaluating peripheral retinal whitened areas.

18.
Ophthalmol Retina ; 7(1): 44-51, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35933107

RESUMO

PURPOSE: To examine the outcomes of pars plana vitrectomy (PPV) with lamellar hole-associated epiretinal proliferation (LHEP) embedding and conventional internal limiting membrane (ILM) peeling for lamellar macular holes (LMHs) with LHEP. DESIGN: Retrospective observational study. SUBJECTS: Forty eyes of 39 consecutive patients with LMHs and LHEP who underwent 3-port PPV with a minimum follow-up of 3 months. METHODS: We compared the results of eyes that underwent PPV with LHEP embedding and ILM peeling (group E) with those of eyes that underwent PPV with ILM peeling only (group I) from September 2010 to September 2021. We confirmed whether the LHEP was embedded using postoperative OCT in all the cases. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity (BCVA) and the development of macular holes (MHs) were assessed. RESULTS: The mean patient age was 73.3 years. The mean follow-up duration was 23.1 months. There were 23 and 17 eyes in groups E and I, respectively. Preoperative BCVA (P = 0.774) and central retinal thickness (CRT) (P = 0.800) did not differ significantly between the 2 groups. The final BCVA in group E was better than that in group I (P = 0.059). The final CRT in group E was thicker than that in group I (P < 0.001). Postoperatively, a significant improvement in BCVA was observed in group E at 3 months (P = 0.001) and at the final visit (P < 0.001). None of the eyes in group E developed postoperative MHs, whereas 5 eyes in group I developed postoperative MHs. CONCLUSIONS: Pars plana vitrectomy using the LHEP embedding technique improved visual acuity significantly and yielded better anatomic outcomes than those with PPV using conventional ILM peeling; MH formation did not occur. Embedding LHEP is more effective than conventional surgical procedures for LMHs.


Assuntos
Membrana Epirretiniana , Perfurações Retinianas , Humanos , Idoso , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Tomografia de Coerência Óptica/métodos , Retina , Proliferação de Células
19.
Ophthalmol Sci ; 3(4): 100339, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37409190

RESUMO

Purpose: To evaluate the relationship between full-thickness macular hole (FTMH) onset and perifoveal posterior vitreous detachment using OCT data. Design: Retrospective study. Participants: A total of 742 patients with FTMH or impending macular hole (MH) in ≥ 1 eye, as determined by ophthalmoscopy and OCT. Methods: Macular holes were staged using OCT results. Patients with the posterior vitreous membrane clearly detected in the OCT images and vitreoretinal adhesion size ≤ 1500 µm-eyes with MH stages 1-3-were included in the study. The contralateral eyes were also included in the analyses if they showed the focal type of vitreomacular adhesion (VMA) (i.e., vitreoretinal adhesion ≤ 1500 µm). The distance between the posterior vitreous membrane and the surface of the retina was defined as the posterior vitreous separation height (PVSH). Using the OCT images, PVSHs of each eye in 4 directions (nasal, temporal, superior, and inferior) at 1 mm from the center of the MH or fovea were calculated. Main Outcome Measures: The main outcome measures were PVSHs according to the MH stage and VMA, the relationship of the foveal inner tear with PVSH, and the likelihood of a foveal inner tear based on the direction. Results: The PVSH trends in each of the 4 directions were as follows: VMA < MH stage 1 = MH stage 2 < MH stage 3. Initial MH stage 2 (onset of FTMH) was defined as the presence of a gap in only 1 of the 4 directions from the center of the MH. With increased PVSH, the likelihood of a gap increased (P = 0.002), and a temporal gap was more likely to occur than a nasal gap (P = 0.002). Conclusions: At FTMH onset, a foveal inner tear likely appears on the temporal side or the side showing a high PVSH value. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36084328

RESUMO

PURPOSE: To report the efficacy of intraoperative optical coherence tomography (iOCT) in locating proliferative membranes or strands subretinally or preretinally during pars plana vitrectomy for proliferative vitreoretinopathy (PVR) or old rhegmatogenous retinal detachment. METHODS: After removing the vitreous and apparent epiretinal membranes, vitreous fluid was exchanged for perfluorocarbon. Lesions of the retinal folds or persistently detached retinas, suspected to be subretinal membrane lesions, were examined using iOCT in three eyes with PVR. RESULTS: iOCT showed subretinal or preretinal structures in all three patients. A subretinal structure with underlying fluid was removed through an intentional hole in a patient. In another patient, a subretinal structure without underlying fluid was not removed. In the remaining patient, the preretinal membranes detected with iOCT could be peeled successfully. CONCLUSION: iOCT examination with perfluorocarbon tamponade effectively identified the correct location of proliferative membranes or strands, namely preretinal or subretinal. This imaging technique helps surgeons determine whether an intentional hole should be made to remove the subretinal structure during vitrectomy. iOCT, combined with perfluorocarbon tamponade, leads to safer and more effective surgery for PVR.

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