Dataset Information

Six3 regulates optic nerve development via multiple mechanisms.

ABSTRACT: Malformations of the optic nerve lead to reduced vision or even blindness. During optic nerve development, retinal ganglion cell (RGC) axons navigate across the retina, exit the eye to the optic stalk (OS), and cross the diencephalon midline at the optic chiasm en route to their brain targets. Many signalling molecules have been implicated in guiding various steps of optic nerve pathfinding, however much less is known about transcription factors regulating this process. Here we show that in zebrafish, reduced function of transcription factor Six3 results in optic nerve hypoplasia and a wide repertoire of RGC axon pathfinding errors. These abnormalities are caused by multiple mechanisms, including abnormal eye and OS patterning and morphogenesis, abnormal expression of signalling molecules both in RGCs and in their environment and anatomical deficiency in the diencephalic preoptic area, where the optic chiasm normally forms. Our findings reveal new roles for Six3 in eye development and are consistent with known phenotypes of reduced SIX3 function in humans. Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations.

SUBMITTER: Samuel A

PROVIDER: S-EPMC4731751 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Six3 regulates optic nerve development via multiple mechanisms.

Samuel Anat A Rubinstein Ariel M AM Azar Tehila T TT Ben-Moshe Livne Zohar Z Kim Seok-Hyung SH Inbal Adi A

Scientific reports 20160129

Malformations of the optic nerve lead to reduced vision or even blindness. During optic nerve development, retinal ganglion cell (RGC) axons navigate across the retina, exit the eye to the optic stalk (OS), and cross the diencephalon midline at the optic chiasm en route to their brain targets. Many signalling molecules have been implicated in guiding various steps of optic nerve pathfinding, however much less is known about transcription factors regulating this process. Here we show that in zebr ...[more]

PMID: 26822689

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Project description:ImportanceThe lack of experienced ophthalmologists limits the early diagnosis of retinal diseases. Artificial intelligence can be an efficient real-time way for screening retinal diseases.ObjectiveTo develop and prospectively validate a deep learning (DL) algorithm that, based on ocular fundus images, recognizes numerous retinal diseases simultaneously in clinical practice.Design, setting, and participantsThis multicenter, diagnostic study at 65 public medical screening centers and hospitals in 19 Chinese provinces included individuals attending annual routine medical examinations and participants of population-based and community-based studies.ExposuresBased on 120 002 ocular fundus photographs, the Retinal Artificial Intelligence Diagnosis System (RAIDS) was developed to identify 10 retinal diseases. RAIDS was validated in a prospective collected data set, and the performance between RAIDS and ophthalmologists was compared in the data sets of the population-based Beijing Eye Study and the community-based Kailuan Eye Study.Main outcomes and measuresThe performance of each classifier included sensitivity, specificity, accuracy, F1 score, and Cohen κ score.ResultsIn the prospective validation data set of 208 758 images collected from 110 784 individuals (median [range] age, 42 [8-87] years; 115 443 [55.3%] female), RAIDS achieved a sensitivity of 89.8% (95% CI, 89.5%-90.1%) to detect any of 10 retinal diseases. RAIDS differentiated 10 retinal diseases with accuracies ranging from 95.3% to 99.9%, without marked differences between medical screening centers and geographical regions in China. Compared with retinal specialists, RAIDS achieved a higher sensitivity for detection of any retinal abnormality (RAIDS, 91.7% [95% CI, 90.6%-92.8%]; certified ophthalmologists, 83.7% [95% CI, 82.1%-85.1%]; junior retinal specialists, 86.4% [95% CI, 84.9%-87.7%]; and senior retinal specialists, 88.5% [95% CI, 87.1%-89.8%]). RAIDS reached a superior or similar diagnostic sensitivity compared with senior retinal specialists in the detection of 7 of 10 retinal diseases (ie, referral diabetic retinopathy, referral possible glaucoma, macular hole, epiretinal macular membrane, hypertensive retinopathy, myelinated fibers, and retinitis pigmentosa). It achieved a performance comparable with the performance by certified ophthalmologists in 2 diseases (ie, age-related macular degeneration and retinal vein occlusion). Compared with ophthalmologists, RAIDS needed 96% to 97% less time for the image assessment.Conclusions and relevanceIn this diagnostic study, the DL system was associated with accurately distinguishing 10 retinal diseases in real time. This technology may help overcome the lack of experienced ophthalmologists in underdeveloped areas.

Dataset Information

Six3 regulates optic nerve development via multiple mechanisms.

Publications

Six3 regulates optic nerve development via multiple mechanisms.

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