Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.397
Filtrar
1.
Cell Prolif ; 53(2): e12757, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916327

RESUMO

OBJECTIVES: To testify that endothelial cells (ECs) induce astrocyte maturation by leukaemia inhibitory factor (LIF) secretion. MATERIALS AND METHODS: In vivo experiments, mice bearing floxed alleles of YAP were crossed with mice expressing a Cre recombinase driven by the endothelial Tek promoter (Tek-Cre) to finally obtain the following three genotypes: YAPf/f , Tek-Cre; YAPf/w , Tek-Cre; and YAPf/f . Retinal vascularization and astrocyte network were evaluated by whole-mount fluorescence and Western blotting. In vitro, experiments were performed in an astrocyte and human microvascular endothelial cell (HMEC-1) coculture model to analyse the mechanisms underlying the effect of endothelial YAP on astrocytes. RESULTS: In vivo, YAPf/f ;Tek-Cre mice showed delayed angiogenesis, sparse vessels and decreased glial fibrillary acidic protein (GFAP)+ astrocytes but aberrant growth of endothelial networks and immature astrocytes (platelet-derived growth factor A, PDGFRA+ astrocytes) overgrowth. In vitro, Yap deletion attenuated the LIF release that delayed the maturation of retinal astrocyte which was consistent with the results of HMEC-1-astrocyte coculture. The effect of YAP overexpression on LIF-LIFR axis in HMEC-1 interferes the GFAP expression of astrocyte. In contrast, LIF protein rescues the astrocytic GFAP expression when EC YAP was inhibited by siRNAs. CONCLUSIONS: We show that EC yes-associated protein (YAP) is not only a critical coactivator of Hippo signalling in retinal vessel development but also plays an essential role in retinal astrocyte maturation by regulating LIF production.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Astrócitos/metabolismo , Fator Inibidor de Leucemia/metabolismo , Retina/metabolismo , Vasos Retinianos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Astrócitos/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Técnicas de Cocultura/métodos , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neovascularização Fisiológica/fisiologia , Neurogênese/fisiologia , Retina/fisiologia , Vasos Retinianos/fisiologia
2.
Eur J Ophthalmol ; 30(1): 48-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30516077

RESUMO

PURPOSE: To quantify vascular and structural macular variables in healthy eyes and to investigate correlations between these variables and age using optical coherence tomography angiography. MATERIALS AND METHODS: A total of 261 eyes of 261 subjects with normal fundus were included. Central macular thickness, ganglion cell layer to inner plexiform layer thickness, outer retina layer thickness, subfoveal choroidal thickness, and choroidal vascularity index were measured using optical coherence tomography. Foveal avascular zone area, vascular density, and flow void area were measured using optical coherence tomography angiography. RESULTS: Vascular density in the superficial capillary plexus was correlated with central macular thickness, ganglion cell layer to inner plexiform layer thickness, and outer retina layer thickness (P < 0.001, P = 0.004, and P < 0.001, respectively). Vascular density in the deep capillary plexus was correlated with central macular thickness and outer retina layer thickness (P = 0.003 and P = 0.001, respectively). Vascular density of choriocapillaris was correlated with vascular density of superficial capillary plexus and deep capillary plexus (P < 0.001 and P = 0.001, respectively). CONCLUSION: Vascular density of choriocapillaris varies with retinal vascular density rather than the structure of choroid using optical coherence tomography angiography. In contrast, retinal vascular density changes as the retinal structure. Our results provide more information about the relationship between retina and choroid.


Assuntos
Corioide/irrigação sanguínea , Vasos Retinianos/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Corioide/diagnóstico por imagem , Estudos Transversais , Feminino , Angiofluoresceinografia/métodos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Adulto Jovem
3.
Invest Ophthalmol Vis Sci ; 60(14): 4865-4871, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747687

RESUMO

Purpose: To evaluate the perfusion status of the retina and choriocapillaris in the area of laser scars on swept-source optical coherence tomography angiography (OCTA) images of eyes previously treated with panretinal photocoagulation (PRP). Methods: Cross-sectional exploratory analysis of swept-source OCTA images, which were retrospectively reviewed for laser scars. The appearance of the capillary networks in the area of previous laser were evaluated following a three-step grading system (normal/sparse/missing capillary network). The superficial and deep capillary plexus of the retina and the choriocapillaris were graded separately. Results: A total of 3140 laser scars in 54 eyes of 31 patients (13 female, mean age 57 ± 12 years) were included in this analysis. In the retina, 6.8% of the superficial and deep capillary network in the area evaluated appeared normal, 58% and 56% sparse, and 35% and 37% missing. Capillary dropout in the retina was not restricted to the area of prior laser treatment. The choriocapillaris decorrelation signal was either sparse (61%) or completely missing (38%) within the laser scar area. The perfusion of the choriocapillaris appeared normal in the area adjacent to laser scars. Conclusions: Capillary non-perfusion in the choriocapillaris was found within the laser scar area. Laser treatment seems to cause sustained non-perfusion of choriocapillaris in the area treated.


Assuntos
Corioide/irrigação sanguínea , Cicatriz/fisiopatologia , Retinopatia Diabética/fisiopatologia , Fotocoagulação a Laser , Vasos Retinianos/fisiologia , Idoso , Capilares/fisiologia , Cicatriz/diagnóstico , Estudos Transversais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
4.
Pregnancy Hypertens ; 17: 203-208, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31487642

RESUMO

OBJECTIVE: The aim of the present study was to examine the effects of preeclampsia on posterior ocular blood flow through optic coherence tomography angiography (OCTA). STUDY DESIGN: The study included preeclamptic pregnant women (group PPW), healthy pregnant women (group HPW) and control non-pregnant women (group CNPW). The blood flow area of retina, optic nerve head and choriocapillaris were assessed through OCTA. RESULTS: Retinal superficial blood flow area (RSBFA) was similar in group PPW, HPW and CNPW (p = 0.101); likewise, there was not any difference in retinal superficial parafoveal vessel density (RSPFD) between the groups (p = 0.685). There was not any difference detected in retinal deep blood flow area (RDBFA) in group PPW, HPW and CNPW), likewise retinal deep parafoveal vessel density (RDPFD) was found similar between the groups (p = 0.184). The choriocapillaris blood flow area (CBFA) was different between the groups (p = 0.000) and less in the group PPW than in group HPW. The CBFA was 1.875 ±â€¯0.05 mm2 in group the PPW, 1.928 ±â€¯0.05 mm2 in the group HPW and 1.464 ±â€¯0.06 mm2 in the group CNPW. Similarly, the optic nerve head blood flow area was lower in the group PPW compared to the group HPW (1.567 ±â€¯0.38 mm2, 1.690 ±â€¯0.20 mm2 and 1.592 ±â€¯0.25 mm2 in the group PPW, group HPW and group CNPW respectively; p = 0.002). CONCLUSION: Posterior segment ocular blood flow may be diminished in preeclamptic women. OCTA may enable to monitor ocular blood flow dynamics and give important clues in the diagnosis of retinal vascular pathologies accompanied by systemic diseases.


Assuntos
Pré-Eclâmpsia/fisiopatologia , Vasos Retinianos/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Gravidez , Fluxo Pulsátil , Fluxo Sanguíneo Regional , Tomografia de Coerência Óptica , Adulto Jovem
5.
Graefes Arch Clin Exp Ophthalmol ; 257(11): 2391-2399, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31378831

RESUMO

PURPOSE: To determine whether water drinking test (WDT) alters choroidal structure using binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images. METHODS: We performed a prospective study of 57 eyes of 57 normal subjects. The intraocular pressure (IOP), EDI-OCT images, and laser speckle flowgraphic images were recorded at baseline, and at 15, 30, 45, and 120 min after the WDT. The EDI-OCT images were converted to binary images using ImageJ software, and we examined luminal area, interstitial area, whole choroidal area, the ratio of luminal area to whole choroidal area (L/W ratio), subfoveal choroidal thickness (SCT), and central retinal thickness (CRT). RESULTS: The luminal area, L/W ratio, whole choroidal area, and IOP were significantly increased 30 min after water drinking; levels returned to the baseline at 120 min. No significant changes were found in the CRT and interstitial area. The fluctuations in the SCT after water intake were significantly correlated with those in the L/W ratio and luminal area but not with those of the interstitial area. The choroidal blood flow velocity was significantly decreased at 30 min. Fluctuations in the luminal area, L/W ratio, and whole choroidal area were significantly correlated with IOP fluctuations. CONCLUSIONS: The changes in the SCT after water drinking were mainly due to the changes in the choroidal vascular space. Dilatations of the choroidal vessels after water drinking may lead to choroidal thickening and subsequent IOP elevation. These findings should be considered in the evaluation of choroidal structure in patients with retinal disease.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Corioide/diagnóstico por imagem , Ingestão de Líquidos/fisiologia , Vasos Retinianos/fisiologia , Tomografia de Coerência Óptica/métodos , Adulto , Corioide/irrigação sanguínea , Estudos Transversais , Feminino , Seguimentos , Humanos , Pressão Intraocular/fisiologia , Fluxometria por Laser-Doppler , Masculino , Estudos Prospectivos , Valores de Referência , Vasos Retinianos/diagnóstico por imagem , Adulto Jovem
6.
Exp Eye Res ; 187: 107766, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31425690

RESUMO

Angiotensin II and aldosterone are the main effectors of the renin-angiotensin aldosterone system (RAAS) and have a central role in hypertension as well as cardiovascular and renal disease. The localization of RAAS components within the retina has led to studies investigating the roles of angiotensin II, aldosterone and the counter regulatory arm of the pathway in vision-threatening retinopathies. This review will provide a brief overview of RAAS components as well as the vascular pathology that develops in the retinal diseases, retinopathy of prematurity, diabetic retinopathy and neovascular age-related macular degeneration. The review will discuss pre-clinical and clinical evidence that modulation of the RAAS alters the development of vasculopathy and inflammation in the aforementioned retinopathies, as well as the emerging role of aldosterone and the mineralocorticoid receptor in central serous chorioretinopathy.


Assuntos
Aldosterona/fisiologia , Angiotensina II/fisiologia , Retinopatia Diabética/fisiopatologia , Vasos Retinianos/fisiologia , Retinite/fisiopatologia , Retinopatia da Prematuridade/fisiopatologia , Degeneração Macular Exsudativa/fisiopatologia , Inibidores da Enzima Conversora de Angiotensina , Humanos , Receptor Tipo 1 de Angiotensina , Sistema Renina-Angiotensina/fisiologia
7.
Exp Eye Res ; 187: 107753, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31408629

RESUMO

The retina is known to have a local renin-angiotensin system (RAS) and dysfunction in the RAS is often associated with diseases of the retinal vasculature that cause irreversible vision loss. Regulation of the retinal vasculature to meet the metabolic needs of the tissues occurs through a mechanism called neurovascular coupling, which is critical for maintaining homeostatic function and support for neurons. Neurovascular coupling is the process by which support cells, including glia, regulate blood vessel calibre and blood flow in response to neural activity. In retinal vascular diseases, this coupling mechanism is often disrupted. However, the role that angiotensin II (Ang II), the main effector peptide of the RAS, has in regulating both the retinal vasculature and neurovascular coupling is not fully understood. As components of the RAS are located on the principal neurons, glia and blood vessels of the retina, it is possible that Ang II has a role in regulating communication and function between these three cell types, and therefore the capacity to regulate neurovascular coupling. This review focuses on components of the RAS located on the retinal neurovascular unit, and the potential of this system to contribute to blood flow modulation in the healthy and compromised retina.


Assuntos
Retinopatia Diabética/fisiopatologia , Microglia/fisiologia , Sistema Renina-Angiotensina/fisiologia , Vasos Retinianos/fisiologia , Angiotensina II/fisiologia , Animais , Humanos
8.
Semin Ophthalmol ; 34(4): 279-286, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31158045

RESUMO

There is growing evidence that vascular dysfunction plays a role in the pathogenesis of glaucoma. The details of this relationship have remained elusive partially due to limitations in our ability to assess blood flow in the optic nerve. Optical coherence tomography angiography (OCTA) has emerged as a promising new technology well positioned to become the first clinically suitable test of optic nerve perfusion. OCTA uses the motion of red blood cells as an intrinsic contrast agent to create reproducible images of microvascular networks rapidly and non-invasively. A significant body of research regarding the use of OCTA in glaucoma has emerged in recent years. This review aims to provide an overview of the basic principles underlying OCTA technology, summarize the current literature regarding the application of OCTA in the management of glaucoma, and address the role of OCTA in explicating the vascular pathogenesis of glaucoma.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Angiofluoresceinografia/métodos , Glaucoma/diagnóstico por imagem , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Glaucoma/fisiopatologia , Humanos , Microcirculação/fisiologia , Fibras Nervosas/patologia , Disco Óptico/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Células Ganglionares da Retina/patologia , Vasos Retinianos/fisiologia
9.
Ophthalmic Surg Lasers Imaging Retina ; 50(5): 302-308, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100161

RESUMO

BACKGROUND AND OBJECTIVE: To correlate subfoveal choriocapillaris (CC) flow density with age using spectral-domain optical coherence tomography angiography (SD-OCTA). PATIENTS AND METHODS: One hundred eighty-three eyes of 94 subjects (66 female, 28 male) were enrolled. Included were healthy subjects between the ages of 21 and 82 years without any history of vitreoretinal disease. Measurements were obtained with software from the OCT device. Significance was defined as a P value of less than .05. RESULTS: The mean age was 43.43 years ± 17.63 years. Correlation between decreasing CC flow density and increasing age was significant (P < .001), with a mean yearly flow decrease of 0.026%. Subfoveal choroidal thickness decreased with advancing age; however, this did not reach a level of significance (P = .069). CONCLUSION: There is a significantly negative correlation between CC flow density and advancing age in healthy subjects, analyzing direct extracted in-built software values from a commercial SD-OCTA device. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:302-308.].


Assuntos
Envelhecimento/fisiologia , Corioide/irrigação sanguínea , Angiofluoresceinografia/métodos , Fluxo Sanguíneo Regional/fisiologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Capilares/fisiologia , Feminino , Fundo de Olho , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/fisiologia , Adulto Jovem
10.
PLoS One ; 14(5): e0215916, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048908

RESUMO

PURPOSE: Blood vessels of the retina provide an easily-accessible, representative window into the condition of microvasculature. We investigated how retinal vessel structure captured in fundus photographs changes with age, and how this may reflect features related to patient health, including blood pressure. RESULTS: We used two approaches. In the first approach, we segmented the retinal vasculature from fundus photographs and then we correlated 25 parameterized aspects ("traits")-comprising 15 measures of tortuosity, 7 fractal ranges of self-similarity, and 3 measures of junction numbers-with participant age and blood pressure. In the second approach, we examined entire fundus photographs with a set of algorithmic CHARM features. We studied 2,280 Sardinians, ages 20-28, and an U.S. based population from the AREDS study in 1,178 participants, ages 59-84. Three traits (relating to tortuosity, vessel bifurcation number, and vessel endpoint number) showed significant changes with age in both cohorts, and one additional trait (relating to fractal number) showed a correlation in the Sardinian cohort only. When using second approach, we found significant correlations of particular CHARM features with age and blood pressure, which were stronger than those detected when using parameterized traits, reflecting a greater signal from the entire photographs than was captured in the segmented microvasculature. CONCLUSIONS: These findings demonstrate that automated quantitative image analysis of fundus images can reveal general measures of patient health status.


Assuntos
Envelhecimento/fisiologia , Microvasos/anatomia & histologia , Microvasos/fisiologia , Vasos Retinianos/anatomia & histologia , Vasos Retinianos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos de Coortes , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Fotografação , Adulto Jovem
11.
Int J Mol Sci ; 20(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027156

RESUMO

We investigated whether the substrate for nitric oxide (NO) production, extracellular l-arginine, contributes to relaxations induced by activating small (SKCa) conductance Ca2+-activated potassium channels. In endothelial cells, acetylcholine increased 3H-l-arginine uptake, while blocking the SKCa and the intermediate (IKCa) conductance Ca2+-activated potassium channels reduced l-arginine uptake. A blocker of the y+ transporter system, l-lysine also blocked 3H-l-arginine uptake. Immunostaining showed co-localization of endothelial NO synthase (eNOS), SKCa3, and the cationic amino acid transporter (CAT-1) protein of the y+ transporter system in the endothelium. An opener of SKCa channels, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) induced large currents in endothelial cells, and concentration-dependently relaxed porcine retinal arterioles. In the presence of l-arginine, concentration-response curves for CyPPA were leftward shifted, an effect unaltered in the presence of low sodium, but blocked by l-lysine in the retinal arterioles. Our findings suggest that SKCa channel activity regulates l-arginine uptake through the y+ transporter system, and we propose that in vasculature affected by endothelial dysfunction, l-arginine administration requires the targeting of additional mechanisms such as SKCa channels to restore endothelium-dependent vasodilatation.


Assuntos
Arginina/farmacologia , Arteríolas/fisiologia , Espaço Extracelular/química , Ativação do Canal Iônico/efeitos dos fármacos , Vasos Retinianos/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Arteríolas/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Óxido Nítrico Sintase Tipo III/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Ratos , Vasos Retinianos/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Suínos
12.
Cutan Ocul Toxicol ; 38(3): 267-273, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31010334

RESUMO

Purpose: To evaluate the effects of intravitreal aflibercept (IVA) treatment on retinal vein parameters and choroidal thickness used in the treatment of diabetic macular oedema (DME). Methods: This retrospective study administered Afyonkarahisar Health Sciences University Department of Ophthalmology. Twenty-nine patients who were diagnosed with naive DME in a single eye were included in the study. A three consecutive, monthly intravitreal injection of 2 mg aflibercept were administered to patients. Each patient's contralateral (untreated) eyes, which did not diagnose DME and did not receive any treatment, were the control group. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery-vein ratio (AVR) values were measured using a semi-automatically computer-based software before the first IVA injection and 30 d after the first, second, and third injections. The main outcome measurements were the central macular thickness (CMT), best-corrected visual acuity (BCVA), subfoveal choroidal thickness (sf-CT), CRAE, CRVE, and AVR. Results: The mean age of patients was 59.25 ± 9.48 years. Patients were 15 males and 14 females. A significant vasoconstriction of the retinal arterioles, a thinning of sf-CT and CMT, and an increase of BCVA have observed in IVA-treated eyes compared to baseline (respectively, p < 0.001, p < 0.001, p < 0.001, p < 0.001). But, no significant differences were found for CRVE and AVR in IVA-treated eyes compared to baseline. No significant difference was found for all parameters in untreated eyes compared to baseline. Conclusions: This study demonstrates that IVA treatment can change retinal blood flow by reducing retinal artery diameter and thinning in the choroid.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Arteríolas/efeitos dos fármacos , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Vasos Retinianos/efeitos dos fármacos , Idoso , Arteríolas/fisiologia , Corioide/diagnóstico por imagem , Corioide/efeitos dos fármacos , Corioide/patologia , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Edema Macular/patologia , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/fisiologia , Vasoconstrição/efeitos dos fármacos
13.
Invest Ophthalmol Vis Sci ; 60(5): 1412-1419, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30943289

RESUMO

Purpose: To assess the variations induced by exercise in retinal vascular density (VD), foveal avascular zone (FAZ) area, and fractal dimension (FD) at the superficial (SCP) and deep (DCP) capillary plexa in healthy subjects by means of optical coherence tomography angiography (OCT-A). Methods: Consecutive healthy subjects were prospectively included into two groups, ranging in age from 18 to 29 years for group 1 and from 30 to 40 years for group 2. Data from 3 × 3-mm OCT-A acquisition centered on the macula at SCP and DCP (VD, FAZ area, and FD), heart rate, and systolic-diastolic blood pressure were collected before and after a 20-minute standardized physical exercise on a stationary bicycle. Results: Both eyes of 32 healthy volunteers were prospectively included (15 in group 1 and 17 in group 2). Mean age was 27 ± 7 years. In the overall analysis and for each group, a decrease of VD at the level of SCP and an increase of FD at the level of DCP were significant after exercise. A significant correlation was found between these modifications of retinal vascularization and the increase of systolic blood pressure induced by exercise. All cardiovascular parameters increased significantly with exercise. No significant difference was found between the two groups, and no incident was reported. Conclusions: A significant correlation was established between systemic cardiovascular modifications (reflected by systolic blood pressure) and local retinal vascularization changes at SCP during exercise. A rest period might be recommended before OCT-A data acquisition, as modifications of cardiovascular parameters could distort retinal vascular data.


Assuntos
Exercício/fisiologia , Fóvea Central/fisiologia , Vasos Retinianos/fisiologia , Adolescente , Adulto , Pressão Sanguínea/fisiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Adulto Jovem
14.
Invest Ophthalmol Vis Sci ; 60(5): 1604-1613, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30995317

RESUMO

Purpose: We address the hypothesis that uncoupling protein 2 (UCP2), a cellular glucose regulator, delays physiologic retinal vascular development (PRVD) by interfering with glucose uptake through glucose transporter 1 (Glut1). Methods: In the rat 50/10 oxygen-induced retinopathy (OIR) model, retinal Glut1 and UCP2 were measured and compared to room air (RA)-raised pups at postnatal day 14 (p14). Pups in OIR and RA received intraperitoneal genipin, an UCP2 inhibitor, or control every other day from p3 until p13. Analyses at p14 included avascular/total retinal area (AVA), Western blots of retinal UCP2 and Glut1, and immunostaining of Glut1 in retinal cryosections. Intravitreal neovascular/total retinal area (IVNV) was analyzed at p18, and electroretinograms were performed at p26. Glut1 and phosphorylated VEGFR2 (p-VEGFR2), glucose uptake, adenosine triphosphate (ATP) production, and cell proliferation were measured in human retinal microvascular endothelial cells (hRMVECs) pretreated with genipin or transfected with UCP2siRNA, Glut1siRNA, or control siRNA when incubated with VEGF or PBS. Results: At p14, OIR pups had increased AVA with decreased Glut1 and increased UCP2 in the retina compared to RA retinas. Intraperitoneal genipin increased retinal Glut1 and reduced AVA. Compared to control, treatment with genipin or knockdown of UCP2 significantly increased Glut1, glucose uptake, ATP production, VEGF-induced p-VEGFR2 and cell proliferation in hRMVECs. Knockdown of Glut1 inhibited VEGF-induced p-VEGFR2. Genipin-treated OIR pups with decreased AVA at p14 had reduced IVNV at p18 and increased amplitudes in a- and b-waves at p26. Conclusions: Extending PRVD by increasing retinal endothelial glucose uptake may represent a strategy to prevent severe retinopathy of prematurity and vision loss.


Assuntos
Retinopatia Diabética/metabolismo , Endotélio Vascular/metabolismo , Glicólise/fisiologia , Vasos Retinianos/fisiologia , Proteína Desacopladora 2/antagonistas & inibidores , Trifosfato de Adenosina/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Colagogos e Coleréticos/farmacologia , Modelos Animais de Doenças , Eletrorretinografia , Feminino , Inativação Gênica , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Injeções Intraperitoneais , Iridoides/farmacologia , Masculino , Oxigênio/toxicidade , Gravidez , Ratos , Ratos Sprague-Dawley , Transfecção , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
PLoS One ; 14(4): e0214685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939178

RESUMO

PURPOSE: Patients with Alzheimer's Disease (AD) exhibit decreased retinal blood flow and vessel density (VD). However, it is not known whether these changes are also present in individuals with early AD (eAD) or amnestic type mild cognitive impairment (aMCI), an enriched pre-AD population with a higher risk for progressing to dementia. We performed a prospective case-control clinical study to investigate whether optical coherence tomography angiography (OCTA) parameters in the macula and disc are altered in those with aMCI and eAD. METHODS: This is a single center study of 32 participants. Individuals with aMCI/eAD (n = 16) were 1:1 matched to cognitively normal controls (n = 16). We evaluated OCTA images of the parafoveal superficial capillary plexus (SCP) and two vascular layers in the peripapillary region, the radial peripapillary capillary (RPC) and superficial vascular complex (SVC). Outcome vascular and structural parameters included VD, vessel length density (VLD), adjusted flow index (AFI) and structural retinal nerve fiber layer (RNFL) thickness. We compared these parameters between the two groups and examined the correlation between OCTA parameters and cognitive performance on the Montreal Cognitive Assessment (MoCA). RESULTS: Cognitively impaired participants demonstrated statistically significant decrease in parafoveal SCP VD and AFI as compared to controls, but no statistically significant difference in peripapillary parameters. Furthermore, we found a significant positive correlation between MoCA scores for the entire study cohort and both the parafoveal SCP VD and peripapillary RPC VLD. CONCLUSION: OCTA shows significant decline in parafoveal flow and VD in individuals with early cognitive impairment related to AD, suggesting that these parameters could have potential utility as early disease biomarkers. In contrast, the presence of larger vascular channels in the peripapillary region may have obscured subtle capillary changes in that region. Overall, the correlation between vascular OCTA parameters and cognitive performance supports further OCTA studies in this population.


Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Vasos Retinianos/fisiologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Casos e Controles , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Processamento de Imagem Assistida por Computador , Macula Lutea/fisiologia , Masculino , Disco Óptico/irrigação sanguínea , Disco Óptico/patologia , Vasos Retinianos/diagnóstico por imagem
16.
Cell ; 176(6): 1248-1264, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30849371

RESUMO

The discovery of vascular endothelial-derived growth factor (VEGF) has revolutionized our understanding of vasculogenesis and angiogenesis during development and physiological homeostasis. Over a short span of two decades, our understanding of the molecular mechanisms by which VEGF coordinates neurovascular homeostasis has become more sophisticated. The central role of VEGF in the pathogenesis of diverse cancers and blinding eye diseases has also become evident. Elucidation of the molecular regulation of VEGF and the transformative development of multiple therapeutic pathways targeting VEGF directly or indirectly is a powerful case study of how fundamental research can guide innovation and translation. It is also an elegant example of how agnostic discovery and can transform our understanding of human disease. This review will highlight critical nodal points in VEGF biology, including recent developments in immunotherapy for cancer and multitarget approaches in neovascular eye disease.


Assuntos
Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/fisiologia , Fatores de Crescimento do Endotélio Vascular/fisiologia , Animais , Humanos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Vasos Retinianos/metabolismo , Vasos Retinianos/fisiologia , Transdução de Sinais/fisiologia , Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
Acta Ophthalmol ; 97(3): 287-295, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30714353

RESUMO

PURPOSE: The aim of the present study was to investigate age-specific normative retinal oxygen saturation values and explore the associated factors in healthy Chinese school-aged children with different refractive statuses. DESIGN: Population-based observational cross-sectional study. METHODS: Children aged 7-19 years were enrolled. Each participant underwent a series of comprehensive ocular examinations, including axial length (AL), cycloplegic refraction and Oxymap T1 imagery following cycloplegia. The acquired oximetry images were measured, and the values of the retinal oxygen saturation parameters were calculated. The independent factors of the retinal oxygen saturation were analysed using multiple linear regression. The oxygen saturation of retinal arteries (SaO2 ) and veins (SvO2 ) as well as the differences between the arteries and veins (AVD) were measured as the main outcomes. RESULTS: In total, 1461 participants were included in the study. The mean age of the participants was 12.1 ± 3.2 years, and 53.0% were boys. The mean SaO2 , SvO2 and AVD values were 83.7 ± 6.4%, 50.1 ± 5.4% and 33.6 ± 5.4%, respectively, and the values increased with age. Girls had higher SvO2 and lower AVD than boys (p < 0.05). The Pearson correlation coefficients among spherical equivalent (SE) and SaO2 , SvO2 and AVD were -0.372, -0.203 and -0.240, respectively (all p < 0.001), while the correlations between AL and SaO2 , SvO2 and AVD were 0.276, 0.106 and 0.221, respectively (all p < 0.001). The myopia group had significantly higher SaO2 , SvO2 and AVD than the emmetropia and hyperopia groups (p < 0.001), but the high myopia group had lower SaO2 and SvO2 than the moderate myopia group. When age, gender, body mass index (BMI), intraocular pressure (IOP) and axial length (AL) were included as factors in the multiple regression, older age was associated with higher SaO2 , SvO2 and AVD, while longer AL was associated with higher SaO2 and AVD. Gender was an independent factor predicting SvO2 , while gender and BMI were the independent factors predicting AVD. Age explained more variance than AL in SaO2 , SvO2 and AVD. CONCLUSIONS: Our population-based study provides age-specific profiles of retinal oxygen saturation in Chinese children and adolescents. Older age and longer AL were important independent factors of increased retinal oxygen saturation.


Assuntos
Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Retina/metabolismo , Vasos Retinianos/fisiologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Oximetria , Valores de Referência , Refração Ocular/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Retina/diagnóstico por imagem , Adulto Jovem
18.
Ophthalmologica ; 242(1): 8-15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30721901

RESUMO

PURPOSE: To investigate retinal and choroidal microvascular changes and structural choroidal involvement in retinal vein occlusion (RVO). METHODS: Retrospective analysis of treatment-naïve macular edema secondary to RVO, studied by optical coherence tomography (OCT) and OCT angiography (OCTA), before and after the loading phase of intravitreal injections of ranibizumab (IVR-LP). OCTA was performed using two different devices: AngioVue RTVue XR Avanti (spectral-domain OCTA) and Zeiss PLEX® Elite 9000 (swept-source OCTA). RESULTS: 30 eyes of 30 consecutive patients (17 branch and 13 central RVO) were included. Central macular thickness and subfoveal choroidal thickness (SCT) were significantly reduced after IVR-LP (p < 0.001 and p = 0.046, respectively). 23 eyes were eligible for OCTA analysis. Baseline vessel density (VD) in deep capillary plexus (DCP) was significantly reduced in RVO eyes compared with fellow eyes (p = 0.03 and p = 0.002 for PLEX® Elite and AngioVue, respectively). After IVR-LP, no significant VD changes in any vascular layer was found. PLEX® Elite VD analysis showed significant differences in DCP between ischemic versus non-is-chemic eyes (p = 0.011). CONCLUSION: OCTA suggests a retinal vascular impairment of DCP but no involvement of choroid in RVO eyes. A greater baseline SCT could be due to a choroidal exudation. OCTA imaged with PLEX® Elite allowed to differentiate ischemic and non-ischemic patients at baseline.


Assuntos
Corioide/irrigação sanguínea , Angiofluoresceinografia/instrumentação , Oclusão da Veia Retiniana/fisiopatologia , Vasos Retinianos/fisiologia , Tomografia de Coerência Óptica/instrumentação , Idoso , Inibidores da Angiogênese/uso terapêutico , Feminino , Angiofluoresceinografia/métodos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab/uso terapêutico , Oclusão da Veia Retiniana/diagnóstico por imagem , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual
19.
Invest Ophthalmol Vis Sci ; 60(2): 694-703, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786274

RESUMO

Purpose: To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA). Methods: Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA. Parafoveal vessel density and adjusted flow index (AFI) were calculated for superficial (SCP), middle (MCP), and deep capillary plexuses (DCP), and then compared between conditions after adjusting for age, refractive error, and scan quality. SCP vessel length density (VLD) was also evaluated. Between-condition capillary images were aligned and subtracted to identify differences. We then analyzed images from 10 healthy subjects during the transition from dark adaptation to ambient light. Results: SCP vessel density was significantly higher while SCP VLD was significantly lower during ambient light and flicker compared to dark adaptation. There was a significant positive mean value for DCP "flicker minus dark or light," suggesting more visible vessels during flicker due to changes in flow, dilation, or vessel recruitment. We found a significant, transient increase in SCP and decrease in both MCP and DCP vessel density during the transition from dark to light. Conclusions: We show evidence suggesting constriction of deeper vessels and dilation of large SCP vessels during the transition from dark to light. This contrasts to redistribution of blood flow to deeper layers during dark adaptation and flicker stimulation.


Assuntos
Capilares/fisiologia , Adaptação à Escuridão/fisiologia , Angiofluoresceinografia/métodos , Macula Lutea/fisiologia , Estimulação Luminosa , Vasos Retinianos/fisiologia , Tomografia de Coerência Óptica/métodos , Adulto , Velocidade do Fluxo Sanguíneo , Capilares/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Hemodinâmica/fisiologia , Humanos , Masculino , Fluxo Sanguíneo Regional/fisiologia , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Acuidade Visual , Adulto Jovem
20.
Invest Ophthalmol Vis Sci ; 60(2): 677-684, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786279

RESUMO

Purpose: To investigate the effect of trabeculectomy on the waveform changes of laser speckle flowgraphy (LSFG) in the optic nerve head (ONH) in patients with glaucoma. Methods: Forty-eight eyes of 48 patients with open angle glaucoma were included in this prospective study. LSFG was performed before and 1, 3, and 6 months after trabeculectomy. Longitudinal changes in average mean blur rate (MBR), blow out score (BOS), resistivity index (RI), falling rate, skew, acceleration time index, and blow out time in the tissue area of the ONH were analyzed by using mixed-effects models. Results: Intraocular pressure (IOP) decreased and ocular perfusion pressure increased significantly at each postoperative time point (P < 0.001, each). BOS increased (P < 0.001, each) and RI decreased (P < 0.001, each) significantly at each postoperative time point, although average MBR and other waveform parameters did not change significantly. Multivariate analyses revealed that younger age (coefficients = -0.13 and 0.0014, P = 0.006 and 0.03 for BOS change and RI change, respectively), worse baseline mean deviation of visual fields (coefficients = -0.18 and 0.0026, P = 0.009 and 0.005), larger IOP reduction (coefficients = -0.29 and 0.0037, P < 0.001, each), and larger pulse rate increase (coefficients = 0.17 and -0.0024, P < 0.001, each) are significantly associated with postoperative BOS increase and RI decrease. Conclusions: Given that postoperative BOS increased and RI decreased with the average MBR remaining unchanged, IOP reduction by trabeculectomy may contribute to stable blood flow throughout the duration of the heartbeat in the tissue area of the ONH.


Assuntos
Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular/fisiologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/fisiologia , Trabeculectomia/métodos , Idoso , Velocidade do Fluxo Sanguíneo , Feminino , Gonioscopia , Frequência Cardíaca/fisiologia , Humanos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fluxo Sanguíneo Regional/fisiologia , Tonometria Ocular , Campos Visuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA