scholarly journals Inherited Retinal Dystrophy in the Mouse: its Appearance in Eyes and Retinae Cultured in vitro

Development ◽  
1958 ◽  
Vol 6 (4) ◽  
pp. 589-592
Author(s):  
D. R. Lucas
Keyword(s):  
Cell Layer ◽  
Retinal Dystrophy ◽  
Visual Cell ◽  
Complete Disappearance ◽  
Cba Mice ◽  
Inherited Retinal Dystrophy

Certain strains of mice, such as C3H, exhibit a recessively inherited retinal dystrophy. This takes the form of a degeneration and complete disappearance of the visual cell layer; it begins on or about the 1 lth day of life and is nearly complete by the 19th day (Sorsby, Roller, Attfield, Davey, & Lucas, 1954). The process is remarkably uniform from litter to litter (Lucas & Newhouse, 1957). In a previous paper (Lucas & Trowell, 1958) it was shown that eyes and retinae taken from 10-day-old normal (CBA) mice could be maintained in vitro for 8 days, during which time their structure was fairly well preserved and differentiation proceeded. In the present work, eyes and retinae from dystrophic strains of mice have been cultured over a similar period to see if the dystrophy developed in vitro. The eyes or retinae of 25 animals from 3 litters of the C3H strain, maintained at the M.R.C.

scholarly journals THE ROLE OF THE PIGMENT EPITHELIUM IN THE ETIOLOGY OF INHERITED RETINAL DYSTROPHY IN THE RAT

1971 ◽  
Vol 49 (3) ◽  
pp. 664-682 ◽  
Author(s):  
Dean Bok ◽  
Michael O. Hall
Keyword(s):  
Cell Death ◽  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Dystrophy ◽  
Visual Cell ◽  
Sprague Dawley ◽  
Inherited Retinal Dystrophy ◽  
Rcs Rats ◽  
Electron Microscopes ◽  
And Control

Visual cell outer segment renewal was studied in eyes of mutant Royal College of Surgeons (RCS) and Sprague-Dawley (control) rats by a combination of microscopy and radioautography with the light and electron microscopes. RCS and control rats were injected with amino acids-3H at 11 days of age. Radioactive rod outer segment discs were assembled at the outer segment base from radioactive proteins synthesized in the rod inner segments. In controls, all radioactive discs assembled at 11 days of age were displaced the length of the outer segments, removed from outer segment tips, and phagocytized by the pigment epithelium by 8 days after injection. In the RCS rats, disc assembly and displacement resembled controls for the first 3 days after injection. However, as disc assembly continued for some time thereafter, a layer of labeled, disorganized, lamellar debris accumulated between the outer segment tips and the pigment epithelium. The buildup of debris was accompanied by visual cell death. At no time during the study was there evidence for phagocytic activity by the pigment epithelium. 61 days after injection, the layer of debris was the only heavily radioactive component in the retina. In the retina of RCS rats, the outer segment renewal mechanism malfunctions because the pigment epithelium does not fulfill its normal phagocytic role. The end result is visual cell death and blindness.

Na-K-activated adenosinetriphosphatase in retinae of rats with and without inherited retinal dystrophy

1970 ◽  
Vol 10 (5) ◽  
pp. 435-438 ◽  
Author(s):  
F.J.M. Daemen ◽  
J.J.H.H.M. de Pont ◽  
F. Lion ◽  
S.L. Bonting
Keyword(s):  
Retinal Dystrophy ◽  
Inherited Retinal Dystrophy

scholarly journals MiR-204 is responsible for inherited retinal dystrophy associated with ocular coloboma

2015 ◽  
Vol 112 (25) ◽  
pp. E3236-E3245 ◽  
Author(s):  
Ivan Conte ◽  
Kristen D. Hadfield ◽  
Sara Barbato ◽  
Sabrina Carrella ◽  
Mariateresa Pizzo ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
In Vitro Assays ◽  
Heterozygous Mutation ◽  
Seed Region ◽  
Medaka Fish ◽  
Inherited Retinal Dystrophies

Ocular developmental disorders, including the group classified as microphthalmia, anophthalmia, and coloboma (MAC) and inherited retinal dystrophies, collectively represent leading causes of hereditary blindness. Characterized by extreme genetic and clinical heterogeneity, the separate groups share many common genetic causes, in particular relating to pathways controlling retinal and retinal pigment epithelial maintenance. To understand these shared pathways and delineate the overlap between these groups, we investigated the genetic cause of an autosomal dominantly inherited condition of retinal dystrophy and bilateral coloboma, present in varying degrees in a large, five-generation family. By linkage analysis and exome sequencing, we identified a previously undescribed heterozygous mutation, n.37C > T, in the seed region of microRNA-204 (miR-204), which segregates with the disease in all affected individuals. We demonstrated that this mutation determines significant alterations of miR-204 targeting capabilities via in vitro assays, including transcriptome analysis. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family, including photoreceptor alterations with reduced numbers of both cones and rods as a result of increased apoptosis, thereby confirming the pathogenic effect of the n.37C > T mutation. Finally, knockdown assays in medaka fish demonstrated that miR-204 is necessary for normal photoreceptor function. Overall, these data highlight the importance of miR-204 in the regulation of ocular development and maintenance and provide the first evidence, to our knowledge, of its contribution to eye disease, likely through a gain-of-function mechanism.

scholarly journals Immunohistochemical Characterization of Phosphorylated Ubiquitin in the Mouse Hippocampus

2020 ◽  
Author(s):  
Kosuke Kataoka ◽  
Andras Bilkei-Gorzo ◽  
Andreas Zimmer ◽  
Toru Asahi
Keyword(s):  
Cell Layer ◽  
Granule Cell Layer ◽  
Phosphatase And Tensin Homolog ◽  
Neuronal Markers ◽  
Tensin Homolog ◽  
Evolutionarily Conserved ◽  
Previous Hypothesis ◽  
Mouse Hippocampus ◽  
And Function

ABSTRACTMitochondrial autophagy (mitophagy) is an essential and evolutionarily conserved process that maintains mitochondrial integrity via the removal of damaged or superfluous mitochondria in eukaryotic cells. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and Parkin promote mitophagy and function in a common signaling pathway. PINK1-mediated ubiquitin phosphorylation at Serine 65 (Ser65-pUb) is a key event in the efficient execution of PINK1/Parkin-dependent mitophagy. However, few studies have used immunohistochemistry to analyze Ser65-pUb in the mouse. Here, we examined the immunohistochemical characteristics of Ser65-pUb in the mouse hippocampus. Some hippocampal cells were Ser65-pUb positive, whereas the remaining cells expressed no or low levels of Ser65-pUb. PINK1 deficiency resulted in a decrease in the density of Ser65-pUb-positive cells, consistent with a previous hypothesis based on in vitro research. Interestingly, Ser65-pUb-positive cells were detected in hippocampi lacking PINK1 expression. The CA3 pyramidal cell layer and the dentate gyrus (DG) granule cell layer exhibited significant reductions in the density of Ser65-pUb-positive cells in PINK1-deficient mice. Moreover, Ser65-pUb immunoreactivity colocalized predominantly with neuronal markers. These findings suggest that Ser65-pUb may serve as a biomarker of in situ PINK1 signaling in the mouse hippocampus; however, the results should be interpreted with caution, as PINK1 deficiency downregulated Ser65-pUb only partially.

scholarly journals Proteoglycan synthesis in two murine bone marrow stromal cell lines

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1777-1783 ◽  
Author(s):  
SL Kirby ◽  
SA Bentley
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Stromal Cell ◽  
Dermatan Sulfate ◽  
Cell Layer ◽  
Gradient Centrifugation ◽  
Exchange Chromatography ◽  
Proteoglycan Synthesis ◽  
Murine Bone Marrow

There is evidence indicating that stromal proteoglycans are an important functional component of the hematopoietic microenvironment. Proteoglycan synthesis was therefore investigated in the MS3–2A and D2XRII hematopoietic stromal cell lines. These lines differ in their capacity to support hematopoiesis in vitro, D2XRII supporting in vitro hematopoiesis, whereas MS3–2A does not. Cells were labeled with 35S- sulfate as precursor, and 4 mol/L guanidine HCl extracts of cells and media were analyzed by ion-exchange chromatography, cesium chloride density gradient centrifugation, and molecular sieve chromatography. Proteoglycans were further examined by enzymatic and chemical digestions. MS3–2A cells produced at least three proteoglycan species. Two chondroitin/dermatan sulfate (CS/DS) proteoglycans, Kav = 0.40 and Kav = 0.68 on Sepharose CL-2B, were present primarily in the medium. The respective glycosaminoglycan molecular weight (mol wt) values were 38 kd and 40 kd. A heparan sulfate (HS) proteoglycan of Kav = 0.58 and glycosaminoglycan mol wt 36 kd was present primarily in the cell layer extract. D2XRII cells synthesized two HS proteoglycans. The larger (Kav = 0.45; glycosaminoglycan mol wt, 30 kd) was of low density on gradient centrifugation and more prominent in the cell layer extracts, whereas the smaller (Kav = 0.68; glycosaminoglycan mol wt, 38 kd) was dense and present mainly in the culture medium. A single CS/DS proteoglycan species of Kav 0.78 and average glycosaminoglycan of mol wt 18 kd was present in roughly equal amounts in the medium and in the cell layer. MS3–2A and D2XRII thus appear phenotypically distinct with respect to proteoglycan synthesis. These differences are discussed in relation to the microenvironmental function of bone marrow stromal elements.

Gene therapy for RPE65 -mediated inherited retinal dystrophy completes phase 3

The Lancet ◽  
2017 ◽  
Vol 390 (10097) ◽  
pp. 823-824 ◽  
Author(s):  
Helena Lee ◽  
Andrew Lotery
Keyword(s):  
Gene Therapy ◽  
Retinal Dystrophy ◽  
Phase 3 ◽  
Inherited Retinal Dystrophy

Comparative analysis of cell distribution in the pigment epithelium and the visual cell layer of chimaeric mice

Development ◽  
1976 ◽  
Vol 36 (2) ◽  
pp. 425-430
Author(s):  
S. Sanyal ◽  
G. H. Zeilmaker
Keyword(s):  
Comparative Analysis ◽  
Cell Layer ◽  
Pigment Epithelium ◽  
Spatial Relation ◽  
Visual Cell ◽  
Cell Distribution ◽  
Retinal Layers

In chimaeras of both rdrdCC↔ + + cc and rdrdcc↔ + + CC combinations two types of distribution were observed. In a majority of the chimaeras both retinal layers were chimaeric; whereas in a few cases the pigment epithelium was chimaeric but the visual cell layer was made of + + cells only. No spatial relation was observed in the distribution of the cells in the two layers. The two eyes of the individuals were nearly always identical with regard to occurrence of chimaerism in the two layers. The findings are discussed in the light of the possible site and mode of expression of the rd gene.

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