Bankable human iPSC-derived retinal progenitors represent a valuable source of multipotent cells.

Retinal progenitor cells (RPCs) are the source of all retinal cell types during retinogenesis. Until now, the isolation and expansion of RPCs has been at the expense of their multipotency. Here, we report simple methods and media for the generation, expansion, and cryopreservation of human induced pluripotent stem-cell derived-RPCs (hiRPCs).

Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue.

Mutations in the ubiquitously expressed pre-mRNA processing factor (PRPF) 31 gene, one of the most common causes of dominant form of Retinitis Pigmentosa (RP), lead to a retina-specific phenotype. It is uncertain which retinal cell types are affected and animal models do not clearly present the RP phenotype observed in PRPF31 patients. Retinal organoids and retinal pigment epithelial (RPE) cells derived from human-induced pluripotent stem cells (iPSCs) provide potential opportunities for studying human PRPF31-related RP.

[Are mini-brains watching you?].

iPSC-derived brain and retinal organoids represent biologically relevant 3D models. A new step in the field of brain and retinal organoids was reached a few months ago with the simultaneous development of brain and eye structures from human iPS cells within the same organoid. Single-cell mRNA sequencing analyses allowed the identification of various ocular and cerebral neuronal populations and electrophysiological recordings confirm the presence of functional and electrically active neurons.

Generation of a Transplantable Population of Human iPSC-Derived Retinal Ganglion Cells.

Optic neuropathies are a major cause of visual impairment due to retinal ganglion cell (RGC) degeneration. Human induced-pluripotent stem cells (iPSCs) represent a powerful tool for studying both human RGC development and RGC-related pathological mechanisms. Because RGC loss can be massive before the diagnosis of visual impairment, cell replacement is one of the most encouraging strategies.

[Retinal organoids as a new tool for understanding and treating retinal diseases].

Generation of retinal organoids from pluripotent stem cells represents an important advance in the study of retinal development and offer new perspectives for the study of retinal diseases missing suitable animal models. Understanding the key stages of retinal development in vertebrates enabled to design protocols to generate self-organized three-dimensional structures derived from pluripotent stem cells and containing all retinal cell types. In addition to their application in basic research, such as the characterization of molecular and cellular mechanisms in retinal pathophysiology, these miniature organs also open up encouraging prospects in the field of cell therapy or the screening of therapeutic molecules, although some obstacles remain to be overcome.

[Photoreceptor cell transplantation for future treatment of retinitis pigmentosa].

In inherited retinal diseases such retinitis pigmentosa, characterized by progressive loss of light sensitive neurons (photoreceptors), cell therapy is now considered as an attractive strategy. Photoreceptor cell replacement would be valuable for restoring function to retinas in a way that is independent from the cause of the disease. With advances in stem cell biology, considerable strides have been made towards the generation of retinal cells, in particular with the development of 3D culture systems allowing the generation of retinal organoids from pluripotent stem cells.

Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells.

The reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) has broad applications in regenerative medicine. The generation of self-organized retinal structures from these iPSCs offers the opportunity to study retinal development and model-specific retinal disease with patient-specific iPSCs and provides the basis for cell replacement strategies. In this study, we demonstrated that the major type of glial cells of the human retina, Müller cells, can be reprogrammed into iPSCs that acquire classical signature of pluripotent stem cells.

Pluripotent Stem Cell-Based Approaches to Explore and Treat Optic Neuropathies.

Sight is a major sense for human and visual impairment profoundly affects quality of life, especially retinal degenerative diseases which are the leading cause of irreversible blindness worldwide. As for other neurodegenerative disorders, almost all retinal dystrophies are characterized by the specific loss of one or two cell types, such as retinal ganglion cells, photoreceptor cells, or retinal pigmented epithelial cells. This feature is a critical point when dealing with cell replacement strategies considering that the preservation of other cell types and retinal circuitry is a prerequisite.

Characterization and Transplantation of CD73-Positive Photoreceptors Isolated from Human iPSC-Derived Retinal Organoids.

Photoreceptor degenerative diseases are a major cause of blindness for which cell replacement is one of the most encouraging strategies. For stem cell-based therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to obtain a homogenous photoreceptor cell population. We confirmed that the cell surface antigen CD73 is exclusively expressed in hiPSC-derived photoreceptors by generating a fluorescent cone rod homeobox (Crx) reporter hiPSC line using CRISPR/Cas9 genome editing.

Generation of Storable Retinal Organoids and Retinal Pigmented Epithelium from Adherent Human iPS Cells in Xeno-Free and Feeder-Free Conditions.

Human induced pluripotent stem cells (hiPSCs) are potentially useful in regenerative therapies for retinal disease. For medical applications, therapeutic retinal cells, such as retinal pigmented epithelial (RPE) cells or photoreceptor precursors, must be generated under completely defined conditions. To this purpose, we have developed a two-step xeno-free/feeder-free (XF/FF) culture system to efficiently differentiate hiPSCs into retinal cells.

Algorithm Variability in the Estimation of Lung Nodule Volume From Phantom CT Scans: Results of the QIBA 3A Public Challenge.

Rationale And Objectives: Quantifying changes in lung tumor volume is important for diagnosis, therapy planning, and evaluation of response to therapy. The aim of this study was to assess the performance of multiple algorithms on a reference data set. The study was organized by the Quantitative Imaging Biomarker Alliance (QIBA).

The protein tyrosine phosphatase interacting protein 51 (PTPIP51) is required for the differentiation of photoreceptors.

Proliferation and differentiation of retinal progenitor cells (RPCs) are tightly controlled by extrinsic cues and distinct combinations of transcription factors leading to the generation of retinal cell type diversity. In this context, we investigated the role of the protein tyrosine phosphatase interacting protein 51 (PTPIP51) in the differentiation of RPCs. The expression pattern of PTPIP51 was analyzed by immunostaining during post-natal retinal development in the rat.

From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium.

Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs).

Involvement of Bcl-2-associated transcription factor 1 in the differentiation of early-born retinal cells.

Retinal progenitor proliferation and differentiation are tightly controlled by extrinsic cues and distinctive combinations of transcription factors leading to the generation of retinal cell type diversity. In this context, we have characterized Bcl-2-associated transcription factor (Bclaf1) during rodent retinogenesis. Bclaf1 expression is restricted to early-born cell types, such as ganglion, amacrine, and horizontal cells.

Comparison of semi-automated and manual methods to measure the volume of liver tumours on MDCT images.

Objective: To retrospectively compare semi-automated and manual volume measurements of malignant liver tumours and inter- and intra-observer variability using commercially available software.

Methods: This study was performed on 60 consecutive patients with untreated liver metastases (30) and HCCs (30), i.e.

Behavioral changes are not directly related to striatal monoamine levels, number of nigral neurons, or dose of parkinsonian toxin MPTP in mice.

Behavioral analyses of mice intoxicated by the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) have generated conflicting results. We therefore analyzed the relationship between behavioral changes, loss of monoamine levels, and loss of dopaminergic cell bodies in groups of mice intoxicated with acute or subchronic MPTP protocols. Despite a higher degree of neuronal loss in the mice intoxicated using subchronic protocols, dopamine loss was severe and homogeneous in the striatum in all groups.

Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats.

Levodopa therapy in Parkinson's disease is mediated by dopamine receptors and, in a recent study, we showed that a Dl full agonist can induce an internalization of D1 dopamine receptors. The aim of the present study was to determine whether levodopa or a dopamine agonist such as ropinirole can also induce the internalization of D1 dopamine receptors in the striatum of control and hemiparkinsonian rats. The distribution of D1 dopamine receptors was analyzed by immunohistochemistry using a specific antibody.

Consequences of dopaminergic denervation on the metabolic activity of the cortical neurons projecting to the subthalamic nucleus in the rat.

Parkinsonian symptoms are currently thought to be related to hyperactivity of the subthalamic nucleus (STN). Because the STN is known to receive many inputs including glutamatergic cortical afferent fibers, we sought to determine whether the activity of this pathway is altered after dopaminergic denervation to estimate its contribution to the impairment of STN activity. A precise mapping of the origin of the corticosubthalamic projection was first performed using retrograde and anterograde tracing methods.

Metabolic effects of nigrostriatal denervation in basal ganglia.

In the past, functional changes in the circuitry of the basal ganglia that occur in Parkinson's disease were primarily analyzed with electrophysiological and 2-deoxyglucose measurements. The increased activity of the subthalamic nucleus (STN) observed has been attributed to a reduction in inhibition mediated by the external segment of the globus pallidus (GPe), secondary to the loss of dopaminergic-neuron influence on D2-receptor-bearing striato-pallidal neurons. More recently, in situ hybridization studies of cytochrome oxidase subunit I have confirmed the overactivity of the STN in the parkinsonian state.

Metabolic activity of excitatory parafascicular and pedunculopontine inputs to the subthalamic nucleus in a rat model of Parkinson's disease.

Using a combination of metabolic measurement and retrograde tracing, we show that the neurons in the pedunculopontine nucleus and parafascicular nucleus of the thalamus that project to the subthalamic nucleus are hyperactive after nigrostriatal dopaminergic denervation in rats. In Parkinson's disease, the loss of dopaminergic neurons induces a cascade of functional changes in the basal ganglia circuitry including a hyperactivity of the subthalamic nucleus. This hyperactivity is thought to be due to a diminution of the inhibitory pallidal influence.

[Enteropathy caused by clofazimine].

A case of Clofazimine enteropathy is reported, diagnosed on the demonstration of red brown birefringent crystals in the small bowel mucosa and submucosa as well as in the mesenteric lymph nodes whereas the clinical and radiological signs appear to be non specific. After the withdrawal of the drug, a clear improvement of the symptoms was achieved only under a gluten free diet. The possibility of such accidents, sometimes lethal, suggests the restriction of clofazimine to leprosy.