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1.
J Glaucoma ; 33(4): 270-276, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506849

RESUMO

PRCIS: Large amount of trabeculotomy with Kahook Dual Blade (KDB) confers better intraocular pressure (IOP) lowering. PURPOSE: We compared the postoperative outcomes of trabeculotomy using the KDB in patients with exfoliation glaucoma (EXG) and primary open angle glaucoma between the 120-degree incision and the 210- to 240-degree incision groups. PATIENTS AND METHODS: We retrospectively analyzed the postoperative outcomes of trabeculotomy performed using the KDB in 101 eyes with EXG and primary open angle glaucoma, who received 120- and 210- to 240-degree incisions at Kumamoto University Hospital between April 25, 2018, and August 11, 2021. Kaplan-Meyer survival curves were used to assess the outcomes. Surgical failure was defined as IOP ≥21 mm Hg (criterion A) and ≥19 mm Hg (criterion B), or an IOP ≤4 mm Hg in either criterion and the need for additional glaucoma surgery. RESULTS: In total, 64 and 37 eyes were included in the 120 and 210- to 240-degree groups, respectively. The 210- to 240-degree group had a higher 1-year success rate compared with the 120-degree group, both when considering all eyes and when considering only those with EXG (P<0.05). CONCLUSIONS: In trabeculotomy with KDB, a 210- to 240-degree incision was more effective than a 120-degree incision in lowering IOP in EXG cases.


Assuntos
Síndrome de Exfoliação , Glaucoma de Ângulo Aberto , Trabeculectomia , Humanos , Síndrome de Exfoliação/cirurgia , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/cirurgia , Estudos Retrospectivos , Pressão Intraocular
2.
Biochem Biophys Res Commun ; 694: 149397, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157582

RESUMO

The first small interfering RNA (siRNA) therapeutic received approval for hereditary transthyretin (ATTRv) amyloidosis, and the patients' lifespan extension by specific inhibition of hepatic synthesis of transthyretin (TTR) is expected. However, ocular amyloidosis in these patients has been a crucial issue. This study aims to evaluate the efficacy and safety of intravitreal TTR siRNA conjugate injection into rabbit eyes. Rabbit (r) TTR siRNA is a screened TTR siRNA conjugate from 53 candidates. The intraocular pressure (IOP) immediately after injection was high despite the 65.9 % decrease of aqueous humor TTR protein levels in the rTTR siRNA group compared with those in the Control siRNA group 2 weeks after the 50 µL siRNA injection. The IOP spike was milder after the 30 µL siRNA injection, and aqueous humor TTR levels decreased by ∼50 % in the rTTR siRNA group, which is consistent with the mRNA levels in the retina. The parameters of dark-adapted, light-adapted, and light-adapted 30 Hz electroretinogram and the thickness of each retinal layer in histological analysis demonstrated no significant differences between the groups. In conclusion, we developed TTR siRNA conjugates for rabbit eyes, and the results indicate that intravitreal TTR siRNA conjugate injection could be a therapeutic option for ocular amyloidosis caused by ATTRv amyloidosis.


Assuntos
Neuropatias Amiloides Familiares , Pré-Albumina , Animais , Humanos , Coelhos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Pré-Albumina/genética , Pré-Albumina/metabolismo , Injeções Intravítreas , Neuropatias Amiloides Familiares/terapia , Neuropatias Amiloides Familiares/tratamento farmacológico
3.
Commun Biol ; 5(1): 776, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918480

RESUMO

Hematopoietic stem cells (HSCs) are produced from the blood vessel walls and circulate in the blood during the perinatal period. However, the migration dynamics of how HSCs enter the bone marrow remain elusive. To observe the dynamics of HSCs over time, the present study develops an intravital imaging method to visualize bone marrow in neonatal long bones formed by endochondral ossification which is essential for HSC niche formation. Endogenous HSCs are labeled with tdTomato under the control of an HSC marker gene Hlf, and a customized imaging system with a bone penetrating laser is developed for intravital imaging of tdTomato-labeled neonatal HSCs in undrilled tibia, which is essential to avoid bleeding from fragile neonatal tibia by bone drilling. The migration speed of neonatal HSCs is higher than that of adult HSCs. Neonatal HSCs migrate from outside to inside the tibia via the blood vessels that penetrate the bone, which is a transient structure during the neonatal period, and settle on the blood vessel wall in the bone marrow. The results obtained from direct observations in vivo reveal the motile dynamics and colonization process of neonatal HSCs during bone marrow formation.


Assuntos
Medula Óssea , Nicho de Células-Tronco , Osso e Ossos , Diagnóstico por Imagem , Células-Tronco Hematopoéticas , Humanos , Recém-Nascido
4.
Sci Rep ; 12(1): 1359, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35079010

RESUMO

To identify the factors associated with the surgical outcomes of Baerveldt glaucoma implant (BGI) for open-angle glaucoma (OAG), the medical records of 51 consecutive OAG patients (age, 43-91 years) who underwent BGI were retrospectively reviewed (median follow-up, 21.7 months). Surgical success was defined as the following postoperative intraocular pressures (IOPs, mmHg): (A) 6 ≤ IOP ≤ 21; (B) 6 ≤ IOP ≤ 18; and (C) 6 ≤ IOP ≤ 15 without loss of light perception or additional glaucoma surgery. Univariate analysis showed that age (all criteria), glaucoma type (criterion C), and preoperative IOP (criteria A and B) were the candidate factors (P < 0.20). When the patients were divided into two groups according to median age (72 years), the success probability was higher in the older group for criteria B (P = 0.047) and C (P = 0.02), and the postoperative IOP was lower in the older group 1-year post-surgery (P = 0.002). Furthermore, the multivariate Cox proportional hazards model revealed that older age was independently associated with surgical success for criteria B (relative risk [RR], 0.94; P = 0.02) and C (RR, 0.94; P = 0.01). In conclusion, older age is a factor associated with the surgical success of BGI for OAG.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Glaucoma/cirurgia , Complicações Pós-Operatórias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Br J Haematol ; 193(6): 1260-1274, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34036571

RESUMO

Adult erythropoiesis entails a series of well-coordinated events that produce mature red blood cells. One of such events is the mitochondria clearance that occurs cell-autonomously via autophagy-dependent mechanisms. Interestingly, recent studies have shown mitochondria transfer activities between various cell types. In the context of erythropoiesis, macrophages are known to interact closely with the early stages of erythroblasts to provide a specialized niche, termed erythroblastic islands (EBI). However, whether mitochondria transfer can occur in the EBI niche has not been explored. Here, we report that mitochondria transfer in the EBI niche occurs in vivo. We observed mitochondria transfer activities from the early stages of erythroblasts to macrophages in the reconstituted in vitro murine EBI via different modes, including tunnelling nanotubes (TNT). Moreover, we demonstrated that Wiskott-Aldrich syndrome protein (WASp) in macrophages mediates TNT formation and mitochondria transfer via the modulation of F-actin filamentation, thus promoting mitochondria clearance from erythroid cells, to potentially enhance their differentiation. Taken together, our findings provide novel insight into the mitochondria clearance machineries that mediate erythroid maturation.


Assuntos
Diferenciação Celular , Eritroblastos/metabolismo , Macrófagos/metabolismo , Mitocôndrias/transplante , Nanotubos/química , Nicho de Células-Tronco , Animais , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo
7.
PLoS One ; 15(11): e0242626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206726

RESUMO

PURPOSE: This study aimed to investigate the effects of substratum stiffness on the sensitivity of human conjunctival fibroblasts to transforming growth factor (TGF)-ß, and to explore the molecular mechanism of action. METHODS: Human conjunctival fibroblasts were cultured on collagen-coated plastic or silicone plates. The stiffness of the silicone plates was 0.2 or 64 kPa. Cells were treated by 2.5 ng/mL TGF-ß2 with or without fibroblast growth factor (FGF)-2 (0-100 ng/mL) for 24 h or 48 h. The protein expression levels were determined by Western blot analysis. Cell proliferation was assessed using the WST-8 assay. RESULTS: FGF-2 suppressed the TGF-ß-induced expression of α-smooth muscle actin (SMA) and collagen type I (Col I), but not fibronectin (FN). Both FGF-2 and TGF-ß2 increased cell proliferation without an additive effect. The induction of α-SMA by TGF-ß2 was decreased on the soft substratum, without any change in the expression level or subcellular location of Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). FGF-2 suppressed TGF-ß-induced α-SMA expression even on the soft substratum. CONCLUSIONS: FGF-2 treatment and a soft substratum suppressed TGF-ß-induced transdifferentiation of conjunctival fibroblasts into myofibroblasts. FGF-2 attenuated the TGF-ß-induced expression of α-SMA, even on a soft substratum.


Assuntos
Proliferação de Células , Transdiferenciação Celular , Fator 2 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Actinas/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular , Colágeno Tipo I/biossíntese , Túnica Conjuntiva , Humanos , Miofibroblastos/citologia , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta2/farmacologia , Proteínas de Sinalização YAP
9.
Cell Rep ; 25(7): 1772-1785.e6, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30428347

RESUMO

During acute myelosuppression or thrombocytopenia, bone marrow (BM) hematopoietic cells respond rapidly to replenish peripheral blood platelets. While the cytokine thrombopoietin (Thpo) both regulates platelet production and maintains HSC potential, whether Thpo controls megakaryocyte (Mk)-lineage differentiation of HSCs is unclear. Here, we show that Thpo rapidly upregulates mitochondrial activity in HSCs, an activity accompanied by differentiation to an Mk lineage. Moreover, in unperturbed hematopoiesis, HSCs with high mitochondrial activity exhibit Mk-lineage differentiation in vitro and myeloid lineage-biased reconstitution in vivo. Furthermore, Thpo skewed HSCs to express the tetraspanin CD9, a pattern correlated with mitochondrial activity. Mitochondria-active HSCs are resistant to apoptosis and oxidative stress upon Thpo stimulation. Thpo-regulated mitochondrial activity associated with mitochondrial translocation of STAT3 phosphorylated at serine 727. Overall, we report an important role for Thpo in regulating rapid Mk-lineage commitment. Thpo-dependent changes in mitochondrial metabolism prime HSCs to undergo direct differentiation to an Mk lineage.


Assuntos
Diferenciação Celular , Linhagem da Célula , Células-Tronco Hematopoéticas/metabolismo , Megacariócitos/citologia , Trombopoetina/metabolismo , Animais , Proliferação de Células , Sobrevivência Celular , Células-Tronco Hematopoéticas/ultraestrutura , Megacariócitos/metabolismo , Camundongos , Mitocôndrias/genética , Mitocôndrias/ultraestrutura , Células Mieloides/citologia , Fosforilação , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Tetraspanina 29/metabolismo , Regulação para Cima
10.
PLoS One ; 13(7): e0201342, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30048529

RESUMO

PURPOSE: To evaluate corneal endothelial cell loss after Baerveldt glaucoma implantation. METHODS: We prospectively evaluated changes in endothelial cell density (ECD) in the cornea of 59 patients (59 eyes) who underwent Baerveldt glaucoma implantation. Tubes were inserted into the anterior chamber in 45 eyes and pars plana in 14 eyes. The primary outcome measure was the change in corneal ECD after Baerveldt glaucoma implantation. Secondary outcome measures included relationships between corneal ECD and optical coherence tomography images of tube parameters (tube-cornea distance and tube-cornea angle) and prognostic factors for corneal ECD loss. RESULTS: Corneal ECD decreased significantly by 9.2% at 12 months after surgery (P = 0.001). In the anterior chamber Baerveldt glaucoma implantation group, corneal ECD at the tube insertion quadrant decreased significantly by 9.6% at 3 months (P = <0.001), 10.7% at 6 months (P = <0.001), and 13.1% at 12 months (P = <0.001). Corneal ECD at the center decreased significantly at 6 months after surgery (7.2% loss; P = 0.012) and at 12 months after surgery (12.1% loss; P = 0.001). Corneal ECD at the contralateral quadrant decreased significantly at 12 months after surgery only (10.3% loss; P = 0.004). In the pars plana Baerveldt glaucoma implantation group, no significant loss of corneal ECD was found in any corneal areas at any post-surgery follow-up visits. Tube-cornea angle was negatively correlated with the rate of corneal ECD loss at the tube insertion quadrant; r = -0.55 (P = 0.0013). In multivariable analyses, exfoliation glaucoma and narrower tube-cornea angle were significant prognostic factors for severe corneal ECD loss (P = 0.0068 and P = 0.046, respectively). CONCLUSIONS: Anterior chamber Baerveldt glaucoma implantation causes corneal endothelial cell loss. Corneal endothelial cell loss starts at the tube insertion quadrant. Exfoliation glaucoma and narrower tube-corneal angle are associated with severe loss of corneal endothelial cells.


Assuntos
Perda de Células Endoteliais da Córnea/etiologia , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Perda de Células Endoteliais da Córnea/patologia , Feminino , Glaucoma/complicações , Glaucoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
11.
Invest Ophthalmol Vis Sci ; 59(2): 776-787, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29392326

RESUMO

Purpose: We aimed to establish purification and culture systems for retinal ganglion cells (RGCs) differentiated from mouse and human pluripotent stem cells (PSC) for in vitro and regenerative medicine studies. Methods: We used a two-step immunopanning method to purify RGCs from mouse and human PSC-derived three-dimensional (3D) retinal organoids. To assess the method, we purified RGCs from 3D retinal organoids derived from embryonic stem cells (ESCs) generated from Thy1-EGFP transgenic (TG) mice. In addition, 3D retinal organoids differentiated from human induced PSCs (iPSCs) were cultured for up to differentiation day (DD) 120, and RGCs were purified by immunopanning. RGC marker expressions were confirmed by immunostaining and reverse transcription-quantitative PCR. The purified RGCs were cultured, and neurite outgrowth was measured and analyzed using an IncuCyte Zoom system. Results: Mouse RGCs purified from Thy1-EGFP TG mouse retinas and the ESC-derived 3D retinas could be maintained for approximately 2 to 3 weeks, expressing the markers BRN3B and SMI-312. Purified RGCs from human iPSC-derived retinal organoids expressed RGC markers and could be maintained for up to 4 weeks. The RGCs collected at DD 90 to 110 extended longer neurites than those collected at younger stages. Conclusions: We successfully purified RGCs from mouse and human PSC-derived 3D retinal organoids cultured for approximately 120 days. RGCs from older retinal organoids would be useful for neurite tracking. This method would be effective not only for studying the pathology of human RGC diseases but also for therapeutic drug studies and RGC transplantation.


Assuntos
Técnicas de Cultura de Células/métodos , Separação Celular/métodos , Células-Tronco Pluripotentes/citologia , Células Ganglionares da Retina/citologia , Animais , Biomarcadores/metabolismo , Western Blotting , Diferenciação Celular , Células Cultivadas , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Crescimento Neuronal , Organoides , Medicina Regenerativa , Células Ganglionares da Retina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Curr Eye Res ; 43(1): 77-83, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28937869

RESUMO

PURPOSE: Axonal transport is fundamental to autophagy in neuronal cells. To understand its biological significance in various conditions, it is necessary to monitor the process of autophagy. However, monitoring methods are often limited to static analyses, such as protein expression and histological observations. Autophagy has multistep process and is highly dynamic; therefore, additional techniques are necessary to study autophagy. In this study, we quantified the dynamics of autophagy-related organelle transport under conditions of dynamic instability and catastrophic disruption of microtubules using in vitro live imaging. MATERIALS AND METHODS: Retinal ganglion cells (RGCs) were isolated from postnatal day 3 Sprague-Dawley rats by immunopanning. After 7 days of culture, acidic organelles were stained by LysoTracker. Dynamics of acidic organelles was quantified using kymographs. Colchicine was used to induce microtubule disruption. Movement of acidic organelles was observed at five time points: before, and at 6, 24, 72, and 120 h after colchicine stimulation. Ethidium homodimer-1 (EthD-1) was used to determine cell viability. RESULTS: The status of axonal transport of acidic organelles (n = 363) from 27 RGCs was classified into four categories: anterograde (1.4%), retrograde (90%), stationary (8.0%), and fluttering (0.28%). Six hours after the induction of microtubule disruption in 14 of 27 RGCs, almost all acidic organelles (n = 236) were stationary. All acidic components had completely stopped moving 24 h later. At 72 h after stimulation, axonal fragmentation, and shrinking and disappearance of soma were observed in 71% of RGCs. Finally, the remaining RGCs became positive for EthD-1. In the control (13 of 27 RGCs), axonal transport was maintained for 120 h and EthD-1-positive RGCs were not observed. CONCLUSION: Almost all acidic organelles were transported retrogradely along the axon, which was inhibited by colchicine. Understanding the dynamics of acidic organelles may provide useful parameters for characterizing autophagy of neuronal cells in pathophysiological conditions.


Assuntos
Transporte Axonal/fisiologia , Microtúbulos/fisiologia , Células Ganglionares da Retina/citologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Modelos Animais , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/metabolismo
13.
Sci Rep ; 7(1): 11345, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28900148

RESUMO

We evaluated bleb fluid images taken after Baerveldt glaucoma implantation. T2-weighted images of bleb fluid were scanned with 3 Tesla magnetic resonance imaging in 52 patients who had undergone tube-shunt surgery using the 350-mm2 endplate Baerveldt glaucoma implant; three-dimensional images were constructed from these images. Bleb fluid images were classified into either a layer of bleb fluid on either side of the endplate (double bleb layer group; n = 24) or one layer outside the endplate (single bleb layer group; n = 28). Despite there being no correlation between the bleb volume and the postoperative IOP (r = -0.080; P = 0.57), the double bleb layer group had significantly lower postoperative IOPs than the single bleb layer group (12.3 ± 3.8 mmHg vs. 14.7 ± 4.1 mmHg, respectively; P = 0.033). The single bleb layer was significantly related to higher numbers of prior intraocular surgeries (relative risk = 2.85; P = 0.0014). Formation of a layer of bleb fluid on either side of the endplate may have resulted in the lower postoperative IOPs after Baerveldt glaucoma implantation. Repeated intraocular surgery adversely affects formation of the double bleb layer.


Assuntos
Vesícula , Implantes para Drenagem de Glaucoma , Glaucoma/diagnóstico , Glaucoma/cirurgia , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Imageamento Tridimensional , Pressão Intraocular , Imageamento por Ressonância Magnética/métodos , Masculino , Prognóstico , Resultado do Tratamento
14.
Acta Ophthalmol ; 95(7): e602-e609, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28627080

RESUMO

PURPOSE: To compare subconjunctival scarring after vitrectomy in rabbit eyes using different gauge systems by analysing anterior segment optical coherence tomography (AS-OCT) images and histological sections. METHODS: Vitrectomy using 20-, 23-, 25- and 27-gauge systems was performed for rabbits. Anterior segment optical coherence tomography (AS-OCT) images of the incision sites were obtained before and at day 1, 7 and 1 month after surgery. We measured the thickness of conjunctival epithelium, stroma, Tenon's capsule and total conjunctiva of these three layers, then determined the preservation rates of the borderlines between each layer. Surgical invasion was estimated by histological observation. RESULTS: The thickness of total conjunctiva, or the thickness of both conjunctival stroma and Tenon's capsule in the 20-gauge group was significantly thicker than that in the 27-gauge group at day 1 and day 7 after surgery. Preservation rates of the conjunctival stroma/Tenon's capsule borderline were significantly lower in the 20-gauge group than in the 25- and 27-gauge groups at day 1, day 7 and 1 month. Preservation rates of the Tenon's capsule/sclera borderline were significantly lower in the 20-gauge group than in the 25- and 27-gauge groups at 1 month. In the 27-gauge group, the number of α-smooth muscle actin-positive fibroblasts was significantly smaller than in the 20-gauge group at day 7. CONCLUSION: Based on the finding of AS-OCT and histology, micro incision vitreous surgery, especially using 27-gauge, contributed to less subconjunctival scarring postoperatively. Therefore, the 27-gauge pars plana vitrectomy (PPV) may be a more effective technique for preserving the structure of conjunctiva.


Assuntos
Cicatriz/etiologia , Túnica Conjuntiva/patologia , Doenças da Túnica Conjuntiva/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Complicações Pós-Operatórias , Tomografia de Coerência Óptica/métodos , Vitrectomia/efeitos adversos , Animais , Cicatriz/diagnóstico , Doenças da Túnica Conjuntiva/diagnóstico , Modelos Animais de Doenças , Desenho de Equipamento , Feminino , Pressão Intraocular , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Agulhas , Coelhos , Vitrectomia/instrumentação
15.
BMC Ophthalmol ; 17(1): 57, 2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-28446148

RESUMO

BACKGROUND: To compare the lamina cribrosa between eyes with and without neovascular glaucoma (NVG) using enhanced depth imaging spectral-domain optical coherence tomography. METHODS: Forty-six patients with proliferative diabetic retinopathy were enrolled in this cross-sectional study. The patients were divided into two groups based on the absence or presence of NVG (the non-NVG group and the NVG group, respectively). The intraocular pressure (IOP), circumpapillary retinal nerve fiber layer (cpRNFL) thickness, anterior lamina cribrosa depth (ALD), and laminar thickness (LT) were compared between the groups. RESULTS: In the non-NVG group, the mean age was 66.2 ± 2.4 (mean ± standard error) years, mean maximum IOP was 18.8 ± 1.8 mmHg, mean cpRNFL thickness was 91.2 ± 3.9 µm, mean ALD was 407.0 ± 22.9 µm, and mean LT was 155.0 ± 4.7 µm. In the NVG group, the mean age was 61.4 ± 2.1 years, mean maximum IOP was 33.1 ± 1.6 mmHg, mean cpRNFL thickness was 73.6 ± 3.4 µm, mean ALD was 403.9 ± 20.1 µm, and mean LT was 156.9 ± 4.2 µm. The IOP was significantly higher and the cpRNFL was significantly thinner in the NVG group (P < 0.001 and P = 0.002, respectively). However, the age, ALD, and LT were not statistically different between the groups (P = 0.151, 0.919, and 0.757, respectively). CONCLUSIONS: Although the cpRNFL was thinner, the structure of the lamina cribrosa was unchanged in the NVG eyes. Axonal loss of the retinal ganglion cells in NVG patients was prior to lamina cribrosa deformation.


Assuntos
Retinopatia Diabética/complicações , Glaucoma Neovascular/diagnóstico , Pressão Intraocular , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Campos Visuais , Idoso , Estudos Transversais , Retinopatia Diabética/diagnóstico , Feminino , Seguimentos , Glaucoma Neovascular/etiologia , Glaucoma Neovascular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Estudos Retrospectivos
17.
Sci Rep ; 6: 33830, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27654856

RESUMO

Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K-tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress.

18.
BMC Ophthalmol ; 16(1): 147, 2016 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-27553843

RESUMO

BACKGROUND: Exercise reduces intraocular pressure (IOP) in the short term. However, it is not known whether exercise contributes to slower glaucomatous visual field defect progression. METHODS: Twenty-four primary open-angle glaucoma or exfoliation glaucoma patients who were evaluated by the Humphrey Field Analyzer (HFA) 24-2 program ≥ four times in 3 years were enrolled. Patients with a history of intraocular surgery in past 3 years or other eye diseases threatening visual fields were excluded. Patients were classified into two groups whether they had exercise habits or not. RESULTS: Eleven patients had exercise habits. The mean ± standard error of IOP and MD slope were 14.8 ± 0.9 mmHg and +0.20 ± 0.20 dB/year in the exercise group and 13.3 ± 0.8 mmHg and -0.53 ± 0.18 dB/year in the non-exercise group (P = 0.24 and P = 0.01, respectively). Higher IOP [odds ratio (OR) = 0.44/1 mmHg increase; P = 0.02] and habitual exercise (OR = 0.04; P = 0.02) reduced the visual field defect progression risk in logistic regression analyses. CONCLUSIONS: Patients with self-reported exercise habits had slower glaucoma progression.


Assuntos
Exercício Físico/fisiologia , Glaucoma/fisiopatologia , Transtornos da Visão , Campos Visuais/fisiologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transtornos da Visão/etiologia , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo Visual
19.
Acta Ophthalmol ; 94(7): e541-e549, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27167027

RESUMO

PURPOSE: To examine whether anterior segment-optical coherence tomography (AS-OCT) can detect conjunctival scarring after transscleral phacoemulsification and whether temporal transscleral phacoemulsification causes scarring in the superior conjunctiva. METHODS: Transscleral phacoemulsification was performed in the superior conjunctiva (superior incision group) or the temporal conjunctiva (temporal incision group). Anterior segment-optical coherence tomography (AS-OCT) images of the superior conjunctiva were obtained before and after surgery. We quantified the thickness of the conjunctiva and preservation rates of the borderlines among the subconjunctival layers. The relationship between the AS-OCT images and histology was evaluated in rabbit eyes with phacoemulsification. RESULTS: Each group comprised 25 patients. At ≤1 month after surgery, the superior conjunctiva was significantly thicker in the superior incision group than the temporal incision group (1 day, 7 days, and 1 month after surgery; p < 0.0001, p < 0.0001, and p < 0.001 respectively); however, there were no significant differences between the two groups at ≥2 months. The borderline of the conjunctival stroma/Tenon's capsule and the borderline of the Tenon's capsule/sclera were preserved significantly better in the temporal incision group after surgery (p < 0.0001). The cell densities in the conjunctiva of the rabbit temporal incision group were unchanged after surgery, whereas the rabbit superior incision group had significantly more neutrophils (p = 0.0001) and myofibroblasts (p < 0.0001) in the superior conjunctiva than the temporal incision group. CONCLUSIONS: Anterior segment-optical coherence tomography (AS-OCT) images can detect conjunctival scarring after transscleral phacoemulsification. The layer structures in the superior conjunctiva are unaffected by temporal transscleral incision.


Assuntos
Cicatriz/etiologia , Doenças da Túnica Conjuntiva/etiologia , Facoemulsificação/efeitos adversos , Actinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Segmento Anterior do Olho/diagnóstico por imagem , Contagem de Células , Cicatriz/diagnóstico por imagem , Doenças da Túnica Conjuntiva/diagnóstico por imagem , Células Epiteliais/patologia , Feminino , Humanos , Implante de Lente Intraocular , Masculino , Estudos Prospectivos , Coelhos , Esclera/diagnóstico por imagem , Esclera/cirurgia , Tomografia de Coerência Óptica
20.
Sci Rep ; 6: 26080, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27184606

RESUMO

We compared early postoperative complications between trabeculectomy and Ex-PRESS implantation. Enrolled patients with 39 primary open-angle or 25 exfoliative glaucoma were randomly assigned to receive trabeculectomy (trabeculectomy group) or Ex-PRESS implantation (Ex-PRESS group). Primary outcomes were early postoperative complications, including postoperative anterior chamber inflammation, frequencies of hyphema, flat anterior chamber, choroidal detachment, hypotonic maculopathy, and the change of visual acuity. The postoperative flare values in trabeculectomy group were higher than those in the Ex-PRESS group (overall, P = 0.004; and 10 days, P = 0.02). Hyphema occurred significantly more frequently in the trabeculectomy group (P = 0.0025). There were no significant differences of the other primary outcomes between the two groups. Additionally, duration of anterior chamber opening was significantly shorter in the Ex-PRESS group (P = 0.0002) and the eyes that had iris contact with Ex-PRESS tube had significantly shallower anterior chambers than did the eyes without the iris contact (P = 0.013). The Ex-PRESS implantation prevented early postoperative inflammation and hyphema in the anterior chamber and shortened the duration of anterior chamber opening. Iris contact with the Ex-PRESS tube occurred more frequently in eyes with open-angle glaucoma and shallow anterior chambers.


Assuntos
Glaucoma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Implantação de Prótese/métodos , Trabeculectomia/métodos , Humanos , Japão
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