scholarly journals Generation of self-organized sensory ganglion organoids and retinal ganglion cells from fibroblasts

2020 ◽  
Vol 6 (22) ◽  
pp. eaaz5858 ◽  
Author(s):  
Dongchang Xiao ◽  
Qinqin Deng ◽  
Yanan Guo ◽  
Xiuting Huang ◽  
Min Zou ◽  
...  

Neural organoids provide a powerful tool for investigating neural development, modeling neural diseases, screening drugs, and developing cell-based therapies. Somatic cells have previously been reprogrammed by transcription factors (TFs) into sensory ganglion (SG) neurons but not SG organoids. We identify a combination of triple TFs Ascl1, Brn3b/3a, and Isl1 (ABI) as an efficient means to reprogram mouse and human fibroblasts into self-organized and networked induced SG (iSG) organoids. The iSG neurons exhibit molecular features, subtype diversity, electrophysiological and calcium response properties, and innervation patterns characteristic of peripheral sensory neurons. Moreover, we have defined retinal ganglion cell (RGC)–specific identifiers to demonstrate the ability for ABI to reprogram induced RGCs (iRGCs) from fibroblasts. Unlike iSG neurons, iRGCs maintain a scattering distribution pattern characteristic of endogenous RGCs. iSG organoids may serve as a model to decipher the pathogenesis of sensorineural diseases and screen effective drugs and a source for cell replacement therapy.

2016 ◽  
Vol 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.


2021 ◽  
Author(s):  
Jilian Goetz ◽  
Zachary F Jessen ◽  
Anne Jacobi ◽  
Adam Mani ◽  
Sam Cooler ◽  
...  

Classification and characterization of neuronal types is critical for understanding their function and dysfunction. Neuronal classification schemes typically rely on measurements of electrophysiological, morphological and molecular features, but aligning these data sets has been challenging. Here, we present a unified classification of retinal ganglion cells (RGCs), the sole retinal output neurons. We used visually-evoked responses to classify 1777 mouse RGCs into 42 types. We also obtained morphological or transcriptomic data from subsets and used these measurements to align the functional classification to publicly available morphological and transcriptomic data sets. We created an online database that allows users to browse or download the data and to classify RGCs from their light responses using a machine-learning algorithm. This work provides a resource for studies of RGCs, their upstream circuits in the retina, and their projections in the brain, and establishes a framework for future efforts in neuronal classification and open data distribution.


2020 ◽  
pp. 9-24
Author(s):  
Peter Bodrogi ◽  
Xue Guo ◽  
Tran Quoc Khanh

The brightness perception of a large (41°) uniform visual field was investigated in a visual psychophysical experiment. Subjects assessed the brightness of 20 light source spectra of different chromaticities at two luminance levels, Lv=267.6 cd/m2 and Lv=24.8 cd/m2. The resulting mean subjective brightness scale values were modelled by a combination of the signals of retinal mechanisms: S-cones, rods, intrinsically photosensitive retinal ganglion cells (ipRGCs) and the difference of the L-cone signal and the M-cone signal. A new quantity, “relative spectral blue content”, was also considered for modelling. This quantity was defined as “the spectral radiance of the light stimulus integrated with the range (380–520) nm, relative to luminance”. The “relative spectral blue content” model could describe the subjective brightness perception of the observers with reasonable accuracy.


Author(s):  
Kyril I. Kuznetsov ◽  
Vitaliy Yu. Maslov ◽  
Svetlana A. Fedulova ◽  
Nikolai S. Veselovsky

Background: The pupillary reaction is controlled by the two main branches of the autonomic nervous system, namely the parasympathetic and sympathetic nervous systems. New discoveries in pupil research has identified that intrinsically photosensitive retinal ganglion cells have an impact on pupillary constriction, particularly sustained pupillary constriction. In the current paper, an objective measurement of sustained pupillary constriction versus the inability to maintain sustained pupillary constriction are observed. The variability in the sustained pupillary constriction, i.e. Alpha Omega pupil, can be objectively identified with the use of modern technology. Case Examples: Two female subjects were adapted to dim illumination, and then two objective pupil measurements of the right eye using Reflex – PLR Analyzer by BrightLamp© (Indianapolis, IN, USA) with sustained illumination were obtained. Subject 1, a 25 year-old-female, demonstrated normal ability of the pupil to constrict and sustain constriction for 10 seconds. She was used as a control for subject 2. Subject 2, a 27 year-old-female, demonstrated the inability to sustain pupillary constriction. She reported being under great psychological stress. Her pupil began to re-dilate between 2 and 3 seconds after the initial constriction. Conclusion: Objective pupillometry can be used to assist in many diagnoses and provides the clinician invaluable information on the state of the individual, and qualifications of sustained pupillary constriction can now be assessed in an objective manner.


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