Dataset Information

Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.

ABSTRACT: The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.

SUBMITTER: Li A

PROVIDER: S-EPMC3749865 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.

Li Airong A Ahsen Osman O OO Liu Jonathan J JJ Du Chuang C McKee Mary L ML Yang Yan Y Wasco Wilma W Newton-Cheh Christopher H CH O'Donnell Christopher J CJ Fujimoto James G JG Zhou Chao C Tanzi Rudolph E RE

Human molecular genetics 20130521 18

The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quan ...[more]

PMID: 23696452

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Project description:Background To evaluate choroidal vascular changes, including choriocapillaris (CC) and middle/large choroidal vessels, in retinitis pigmentosa (RP) patients using wide-angle optical coherence tomography angiography (OCTA) and to determine whether changes in the choroidal vascularity have a relationship with visual function and retinal structural changes. Methods 34 patients with a confirmed diagnosis of RP and 48 controls were recruited. All patients underwent detailed ophthalmologic and imaging examinations, including two types of OCTA (Optovue, 3?×?3?mm, 6?×?6?mm; VG-200, 12?×?12?mm). CC defects were defined according to the choroidal vascular structure in five degrees. To evaluate middle and large choroidal vascular changes, the choroidal vascularity index (CVI), which was the luminance volume to the total choroidal volume, was used. Results Defects of choroidal vascularity of RP eyes were detected in comparison to control eyes. The defects were observed in the CC layer with a concentric or lobular pattern at different degrees. CVI, which was used to reflect middle/large choroidal vascularity, decreased in the perifoveal, pararetinal and periretinal regions in the RP eyes. CC defects degree were correlated with the BCVA (p?=?0.001, r?=???0.556), the Humphrey indexes (mean deviation, MD, p?<?0.001, r?=???0.673; PVF, p?=?0.003, r?=???0.639; 10° mean sensitivity, 10° MS, p?=?0.002, r?=???0.651) and microperimetry index (mean sensitivity, MS, p?<?0.001, r?=???0.807). The preserved CC area (mean value: 28.65?±?12.50?mm2) was negatively correlated with MS measured by microperimetry (p?=?0.005, r?=???0.449). Ordinary regression analysis revealed that the CC defect degree was associated with the CVI of perifovea (p?=?0.002, 95% CI: ??102.14 to ??24.01), the EZ length (p?=?0.006, 95% CI: ??0.006 to ??0.001) and the VAD (vascular area density) of the DCP (deep capillary plexus) in the fovea (p?=?0.022, 95% CI: 0.038–0.478). No correlations were detected between BCVA and CVI in any retinal regions. No correlations were found between the CVI and the VAD in any retinal regions. Conclusion The choroidal vascularity was widely defected in RP. Choriocapillaris and middle/large choroidal vascularity defects were correlated with each other. Visual function and retinal structural changes were found to be associated with choriocapillaris defects but not with middle/large choroidal vascular defects.

Project description:PurposeTo investigate factors associated with dropout of the parapapillary deep retinal layer microvasculature assessed by optical coherence tomography angiography (OCTA) in glaucomatous eyes.DesignCross-sectional study.ParticipantsSeventy-one eyes from 71 primary open-angle glaucoma (POAG) patients with β-zone parapapillary atrophy (βPPA) enrolled in the Diagnostic Innovations in Glaucoma Study.MethodsParapapillary deep-layer microvasculature dropout was defined as a complete loss of the microvasculature located within the deep retinal layer of the βPPA from OCTA-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) also was calculated using OCTA. Choroidal thickness and presence of focal lamina cribrosa (LC) defects were determined using swept-source optical coherence tomography.Main outcome measuresPresence of parapapillary deep-layer microvasculature dropout. Parameters including age, systolic and diastolic blood pressure, axial length, intraocular pressure, disc hemorrhage, cpVD, visual field (VF) mean deviation (MD), focal LC defects βPPA area, and choroidal thickness were analyzed.ResultsParapapillary deep-layer microvasculature dropout was detected in 37 POAG eyes (52.1%). Eyes with microvasculature dropout had a higher prevalence of LC defects (70.3% vs. 32.4%), lower cpVD (52.7% vs. 58.8%), worse VF MD (-9.06 dB vs. -3.83 dB), thinner total choroidal thickness (126.5 μm vs. 169.1 μm), longer axial length (24.7 mm vs. 24.0 mm), larger βPPA (1.2 mm2 vs. 0.76 mm2), and lower diastolic blood pressure (74.7 mmHg vs. 81.7 mmHg) than those without dropout (P < 0.05, respectively). In the multivariate logistic regression analysis, higher prevalence of focal LC defects (odds ratio [OR], 6.27; P = 0.012), reduced cpVD (OR, 1.27; P = 0.002), worse VF MD (OR, 1.27; P = 0.001), thinner choroidal thickness (OR, 1.02; P = 0.014), and lower diastolic blood pressure (OR, 1.16; P = 0.003) were associated significantly with the dropout.ConclusionsSystemic and ocular factors including focal LC defects more advanced glaucoma, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the parapapillary deep-layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between parapapillary deep-layer microvasculature dropout and systemic and ocular factors.

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Dataset Information

Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.

Publications

Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.

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