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1.
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
2.
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.

3.
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
4.
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
5.
Biomed Hub ; 7(2): 99-105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262676

RESUMO

Introduction: This study aimed to describe the quantitative features of the microvasculature in the cystic lesions of branch retinal vein occlusion (BRVO). Methods: A total of 43 eyes with BRVO, treated with anti-vascular endothelial growth factor therapy, were analyzed. Using wide-field swept-source optical coherence tomography angiography (OCTA), en face OCT images were obtained by depth-integrated reflectivity of the retina, and vascular density (VD), vascular length (VL), vascular lacunarity, and fractal dimension (FD) were evaluated in a 12 × 12-mm area of retinal nonperfusion. Results: The mean area of affected lesions was 38.7 ± 19.8 mm2, and cystic lesions were 8.5 ± 10.1 mm2. VD, VL, and FD were significantly decreased in the cystic lesions compared to other affected lesions in the same eyes (p = 0.0010, p = 0.0001, and p = 0.0003, respectively) and in all eyes (p = 0.0281, p = 0.0050, and p < 0.0001, respectively). VD in cystic lesions within the vascular arcade (25 eyes) correlated with best-corrected visual acuity on OCTA (r = -0.433, and p = 0.0492). Conclusions: Vascular structure in the cystic lesions was unpreserved compared to the other lesions in BRVO. These findings may help in understanding the pathophysiology of retinal edema in BRVO.

6.
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.

7.
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
8.
Sci Rep ; 11(1): 21947, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34754047

RESUMO

Although choriocapillaris flow deficit (CFD) around choroidal neovascularization (CNV) is less associated with CNV activity in myopic eyes, no reports are investigating its size as an indicator of CNV activity. We investigated the relationship between CFD and high myopia-related CNV. In this retrospective, observational study, patients underwent optical coherence tomography angiography (OCTA) with split-spectrum amplitude-decorrelation angiography for diagnosing pathological myopic CNV (mCNV); CFD features around CNV margins were evaluated. Of the 33 eyes (30 patients), 11 (33.3%) had active mCNV, and 22 (66.7%) had inactive CNV. Six eyes (18.2%) were treatment-naïve, while the remainder previously underwent anti-vascular endothelial growth factor therapy. On OCTA, blood flow signals were detected in CNV in the outer retinal layer in 28 (84.8%) eyes, including all active cases (11 cases) and 17 (77.3%) of 22 inactive cases. CNV flow signal size correlated significantly with activity (P < 0.001). CFD around CNV was observed in 24 eyes (72.7%), including all active cases (11 cases) and 13 (59.1%) of 22 inactive cases. CFD size correlated significantly with CNV activity (P < 0.001). The size of both the CFD area around CNV and CNV flow signal area are useful indicators of CNV activity in eyes with mCNV, which may help determine treatment timing.


Assuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/complicações , Miopia/complicações , Fluxo Sanguíneo Regional , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Corioide/diagnóstico por imagem , Corioide/patologia , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/patologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem
9.
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
10.
JCI Insight ; 5(12)2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32437334

RESUMO

Abnormal subretinal neovascularization is a characteristic of vision-threatening retinal diseases, including macular telangiectasia (MacTel) and retinal angiomatous proliferation (RAP). Subretinal neovascular tufts and photoreceptor dysfunction are observed in very-low-density lipoprotein receptor (Vldlr-/-) mutant mice. These changes mirror those observed in patients with MacTel and RAP, but the pathogenesis is largely unknown. In this study, we show that retinal microglia were closely associated with retinal neovascular tufts in Vldlr-/- mice and retinal tissue from patients with MacTel; ablation of microglia/macrophages dramatically prevented formation of retinal neovascular tufts and improved neuronal function, as assessed by electroretinography. Vldlr-/- mice with retinal pigmented epithelium-specific (RPE-specific) Vegfa had greatly reduced subretinal infiltration of microglia/macrophages, subsequently reducing neovascular tufts. These findings highlight the contribution of microglia/macrophages to the pathogenesis of neovascularization, provide valuable clues regarding potential causative cellular mechanisms for subretinal neovascularization in patients with MacTel and RAP and suggest that targeting microglia activation may be a therapeutic option in these diseases.


Assuntos
Degeneração Macular/patologia , Microglia/patologia , Neovascularização Retiniana/patologia , Epitélio Pigmentado da Retina/patologia , Animais , Modelos Animais de Doenças , Camundongos Knockout , Neovascularização Patológica/patologia , Retina/patologia , Vasos Retinianos/patologia
11.
Sci Rep ; 9(1): 12230, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439887

RESUMO

We report to evaluate if disorganization of the retinal inner layers (DRIL) obtained by swept-source optical coherence tomography (SS-OCT) predicts the postoperative best-corrected visual acuity (BCVA) to treat proliferative diabetic retinopathy (PDR). Twenty-one eyes of 21 patients who underwent vitrectomy for PDR were studied retrospectively. BCVA and SS-OCT images were obtained until 6 months postoperatively. The associations between BCVA and SS-OCT parameters measured in a 1-mm central foveal area were evaluated. The DRIL length, external limiting membrane disruption, and ellipsoid zone (EZ) disruption 1 month postoperatively were associated positively with the postoperative logarithm of the minimum angle of resolution (logMAR) BCVA at 1, 3, and 6 months (1 month, p = 0.009, p = 0.013, p = 0.001; 3 months, p = 0.03, p = 0.021, p = 0.002; and 6 months, p = 0.021, p = 0.013, and p = 0.005, respectively). The eyes with a 500-µm or longer DRIL 1 month postoperatively (19%, 4/21 eyes) had significantly worse VA at 1, 3, and 6 months postoperatively (p = 0.007, p = 0.008, and p = 0.020, respectively). Multilinear regression analysis of all visits until 6 months postoperatively showed that the DRIL was correlated more significantly (p = 0.0004) with logMAR BCVA than the disrupted EZ length. The DRIL in the early postoperative period may predict the visual outcomes after treating PDR.


Assuntos
Retinopatia Diabética/fisiopatologia , Retina/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Retina/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia
12.
Sci Rep ; 9(1): 10262, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311970

RESUMO

We evaluated regression of iris neovascularization (INV) using en-face anterior-segment optical coherence tomography angiography (AS-OCTA) after anti-vascular endothelial growth factor (VEGF) therapy. Seven consecutive eyes with INV were examined before and after anti-VEGF therapy, and all AS-OCTA scans were obtained using a swept-source OCTA system with an anterior-segment lens adapter. Slit-lamp microscopy photography and anterior indocyanine green angiography also were performed. Quantitative analyses of the vascular density, vascular lacunarity, and fractal dimension on AS-OCTA images were performed. AS-OCTA visualized the INV as signals around the pupillary margin, which corresponded to the vasculature confirmed by slit-lamp microscopy. After anti-VEGF drug injection, regression of INV was observed by AS-OCTA in all eyes (100%). The vascular density decreased and vascular lacunarity increased significantly after anti-VEGF therapy. This pilot study demonstrated the ability of AS-OCTA not only to detect but also to evaluate INV. Further study is warranted to improve the algorithm for delineating the iris vasculature to decrease artifacts.


Assuntos
Doenças da Íris/diagnóstico por imagem , Iris/irrigação sanguínea , Neovascularização Patológica/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Idoso , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Feminino , Angiofluoresceinografia/métodos , Humanos , Iris/diagnóstico por imagem , Doenças da Íris/tratamento farmacológico , Doenças da Íris/fisiopatologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
14.
Dev Cell ; 48(2): 151-166.e7, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30639056

RESUMO

TNF-α is a pleiotropic cytokine that has the potential to induce apoptosis under inflammation. How endothelial cells (ECs) are spared from this fate in inflammatory environments where TNF-α is present is not known. Here, we show that TGF-ß-activated kinase 1 (TAK1) ensures EC survival and maintains vascular integrity upon TNF-α stimulation. Endothelial-specific TAK1 knockout mice exhibit intestinal and liver hemorrhage due to EC apoptosis, leading to vascular destruction and rapid death. This EC apoptosis was induced by TNF-α from myeloid cells responding to intestinal microbiota. TNF-α secretion associated with inflammation also induced vascular defects in inflamed organs. Additionally, we determined that TAK1 deletion in tumor ECs resulted in blood vessel and hence tumor regression. Our results illuminate mechanisms ensuring survival of intestinal and liver ECs under physiological conditions and ECs of other organs under inflammatory conditions that could be exploited for anti-angiogenic therapy to treat cancer.


Assuntos
Células Endoteliais/patologia , Hepatócitos/citologia , Inflamação/patologia , MAP Quinase Quinase Quinases/metabolismo , Animais , Apoptose/fisiologia , Camundongos Transgênicos , Transdução de Sinais/fisiologia
15.
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
16.
J Clin Invest ; 127(1): 199-214, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27918307

RESUMO

Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF inhibition could reduce cellular complement regulatory capacity. VEGF antagonism also increased markers of endothelial cell activation, which was partially reduced by genetic complement inhibition. Together, these results suggest that VEGF protects the retinal and glomerular microvasculature, not only through VEGFR2-mediated vasculotrophism, but also through modulation of local complement proteins that could protect against complement-mediated damage. Though further study is warranted, these findings could be relevant for patients receiving VEGF antagonists.


Assuntos
Fator H do Complemento/metabolismo , Proteínas do Olho/metabolismo , Podócitos/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Animais , Fator H do Complemento/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas do Olho/antagonistas & inibidores , Proteínas do Olho/genética , Feminino , Humanos , Nefropatias/genética , Nefropatias/metabolismo , Nefropatias/patologia , Degeneração Macular/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Masculino , Camundongos , Camundongos Knockout , Podócitos/patologia , Proteína Quinase C-alfa/genética , Proteína Quinase C-alfa/metabolismo , Epitélio Pigmentado da Retina/patologia , Microangiopatias Trombóticas/genética , Microangiopatias Trombóticas/metabolismo , Microangiopatias Trombóticas/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
Nat Commun ; 6: 7925, 2015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26239146

RESUMO

Anti-angiogenic drugs targeting vascular endothelial cell growth factor receptor have provided modest clinical benefit, in part, owing to the actions of additional angiogenic factors that stimulate tumour neoangiogenesis in parallel. To overcome this redundancy, approaches targeting these other signalling pathways are required. Here we show, using endothelial cell-targeted mice, that the small GTPase Arf6 is required for hepatocyte growth factor (HGF)-induced tumour neoangiogenesis and growth. Arf6 deletion from endothelial cells abolishes HGF-stimulated ß1 integrin recycling. Pharmacological inhibition of the Arf6 guanine nucleotide exchange factor (GEF) Grp1 efficiently suppresses tumour vascularization and growth. Grp1 as well as other Arf6 GEFs, such as GEP100, EFA6B and EFA6D, regulates HGF-stimulated ß1 integrin recycling. These findings provide insight into the mechanism of HGF-induced tumour angiogenesis and offer the possibility that targeting the HGF-activated Arf6 signalling pathway may synergize with existing anti-angiogenic drugs to improve clinical outcomes.


Assuntos
Fatores de Ribosilação do ADP/genética , Células Endoteliais/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Integrina beta1/metabolismo , Melanoma Experimental/irrigação sanguínea , Neovascularização Patológica/genética , RNA Mensageiro/metabolismo , Retina/metabolismo , Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Ensaios de Migração Celular , Ensaio de Imunoadsorção Enzimática , Adesões Focais/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Imuno-Histoquímica , Técnicas In Vitro , Melanoma Experimental/genética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Transplante de Neoplasias , Neovascularização Patológica/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Invest Ophthalmol Vis Sci ; 56(1): 640-6, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25574041

RESUMO

PURPOSE: To assess the morphology of areas of complete retinal nonperfusion in eyes with branch retinal vein occlusion (BRVO) by en face images of optical coherence tomography (OCT). METHODS: Forty-six eyes with BRVO that underwent swept-source OCT (SS-OCT) and fluorescein angiography were enrolled. Depth-integrated images of the neural retina delineated by automated segmentation algorithm were obtained using SS-OCT. The findings in a 6 × 6-mm area on en face SS-OCT scans at the area of retinal nonperfusion were evaluated. RESULTS: Retinal nonperfusion was detected in 25 eyes. Of these, 20 (80%) eyes had multiple concaves of low reflectivity within an area of reticular high reflectivity (honeycomb sign) on depth-integrated images at the area corresponding to retinal nonperfusion. The mean area of retinal nonperfusion and honeycomb sign were 6.72 ± 4.10 mm2 and 4.19 ± 3.37 mm2, respectively. The area of retinal nonperfusion was correlated significantly (r = 0.53, P < 0.001) with the area of the honeycomb sign. The mean retinal thickness in eyes with a honeycomb sign increased significantly (P = 0.017) compared with eyes without a honeycomb sign. Furthermore, after anti-VEGF injection, the mean area of honeycomb sign decreased significantly (P = 0.0013), from 4.23 mm(2) to 0.48 mm(2). CONCLUSIONS: Depth-integrated OCT images with automated layer segmentation showed a two-dimensional honeycomb-like structure in retinal nonperfusion with retinal edema. In eyes with BRVO, the thickness of retina did not decrease but increased due to retinal cyst in spite of neural retinal thinning.


Assuntos
Isquemia/patologia , Oclusão da Veia Retiniana/diagnóstico , Veia Retiniana/patologia , Tomografia de Coerência Óptica , Idoso , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab , Feminino , Angiofluoresceinografia , Humanos , Pressão Intraocular/fisiologia , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/fisiopatologia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
19.
Br J Ophthalmol ; 98(9): 1221-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24692747

RESUMO

AIM: To examine the long-term outcomes of full macular translocation (FMT) for myopic choroidal neovascularisation (mCNV). METHODS: We evaluated a consecutive case series of 60 eyes with mCNV that underwent FMT. We assessed the best-corrected visual acuity (BCVA), fundus photographs and fluorescein angiography images, and evaluated the anatomic and visual outcomes. RESULTS: The mean follow-up period was 76.3 months. The macula was relocated successfully in all eyes. The mean distance of macular translocation was 2842 µm. The baseline BCVA was 0.78 logarithm of the minimum angle of resolution (logMAR) unit; the logMAR BCVA values at 1, 3 and 5 years postoperatively significantly (p<0.001) improved to 0.54 at 1 year and then remained stable. The new fovea was associated with enlargement of the myopic chorioretinal atrophy in 19 (31.7%) eyes. Subfoveal or juxtafoveal CNV at the translocated new fovea developed in five (8.3%) eyes. CONCLUSIONS: FMT for mCNV maintained the improvement in VA for more than 5 years. However, postoperative complications and progression of chorioretinal atrophy due to myopia still seem to limit the visual improvement after FMT for mCNV.


Assuntos
Neovascularização de Coroide/cirurgia , Macula Lutea/transplante , Miopia Degenerativa/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/fisiopatologia , Complicações Pós-Operatórias , Resultado do Tratamento , Acuidade Visual
20.
Clin Ophthalmol ; 8: 471-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24600201

RESUMO

BACKGROUND: The purpose of this study was to evaluate visual outcomes of arteriovenous sheathotomy for macular edema due to branch retinal vein occlusion (BRVO). METHODS: The medical records of 45 eyes from 45 patients who had undergone vitrectomy surgery with arteriovenous sheathotomy for BRVO were studied. Forty-five eyes of 45 patients with a BRVO but without intervention were studied as the control group. The best-corrected visual acuity and central macular thickness were compared between the two groups at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: Improvement of best-corrected visual acuity was 0.42 logarithm of the minimum angle of resolution (logMAR) units in the sheathotomy group and 0.22 logMAR units in the control group (P=0.007). The mean postoperative central macular thickness was significantly thinner in the sheathotomy group at 1 month (P=0.01), but not at 3, 6, and 12 months (P=0.75, P=0.81, and P=0.46, respectively). Improvement of best-corrected visual acuity at 12 months was significantly correlated with baseline best-corrected visual acuity, age, duration of symptoms, and sheathotomy (P<0.05). CONCLUSION: Arteriovenous sheathotomy for BRVO improves best-corrected visual acuity significantly more than the natural course of the BRVO disease process.

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