scholarly journals Changes in endolysosomal organization define a pre-degenerative state in the crumbs mutant Drosophila retina

2019 ◽  
Author(s):  
Rachel S. Kraut ◽  
Elisabeth Knust
Keyword(s):  
Nervous System ◽  
Retinal Degeneration ◽  
Intracellular Trafficking ◽  
Spatial Organization ◽  
Photoreceptor Cells ◽  
Epithelial Polarity ◽  
Biological Origin ◽  
Early Signs ◽  
Polarity Gene

AbstractMutations in the epithelial polarity gene crumbs (crb) lead to retinal degeneration in Drosophila and in humans. The overall morphology of the retina and its deterioration in Drosophila crb mutants has been well-characterized, but the cell biological origin of the degeneration is not well understood. Degenerative conditions in the retina and elsewhere in the nervous system often involve defects in degradative intracellular trafficking pathways. So far, however, effects of crb on the endolysosomal system, or on the spatial organization of these compartments in photoreceptor cells have not been described. We therefore asked whether photoreceptors in crb mutants exhibit alterations in endolysosomal compartments under pre-degenerative conditions, where the retina is still morphologically intact. Data presented here show that, already well before the onset of degeneration, Arl8, Rab7, and Atg8-carrying endolysosomal and autophagosomal compartments undergo changes in morphology and positioning with respect to each other in crb mutant retinas. We propose that these changes may be early signs of the degeneration-prone condition in crb retinas.

scholarly journals Nutraceutical Supplementation Ameliorates Visual Function, Retinal Degeneration, and Redox Status in rd10 Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1033
Author(s):  
Lorena Olivares-González ◽  
Sheyla Velasco ◽  
Isabel Campillo ◽  
David Salom ◽  
Emilio González-García ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Antioxidant Properties ◽  
Photoreceptor Cells ◽  
Redox Status ◽  
Inherited Retinal Dystrophies ◽  
Stress Markers ◽  
Retinal Dystrophies ◽  
Progressive Degeneration ◽  
Light Stimuli

Background: Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In this study, we investigated the effect of a mixture of nutraceuticals with antioxidant properties (NUT) on retinal degeneration in rd10 mice, a model of RP. Methods: NUT was orally administered to rd10 mice from postnatal day (PD) 9 to PD18. At PD18 retinal function and morphology were examined by electroretinography (ERG) and histology including TUNEL assay, immunolabeling of microglia, Müller cells, and poly ADP ribose polymers. Retinal redox status was determined by measuring the activity of antioxidant enzymes and some oxidative stress markers. Gene expression of the cytokines IL-6, TNFα, and IL-1β was assessed by real-time PCR. Results: NUT treatment delayed the loss of photoreceptors in rd10 mice partially preserving their electrical responses to light stimuli. Moreover, it ameliorated redox status and reduced inflammation including microglia activation, upregulation of cytokines, reactive gliosis, and PARP overactivation. Conclusions: NUT ameliorated retinal functionality and morphology at early stages of RP in rd10 mice. This formulation could be useful as a neuroprotective approach for patients with RP in the future.

Transplantation of human central nervous system stem cells - neuroprotection in retinal degeneration

2012 ◽  
Vol 35 (3) ◽  
pp. 468-477 ◽  
Author(s):  
Trevor J. McGill ◽  
Benjamin Cottam ◽  
Bin Lu ◽  
Shaomei Wang ◽  
Sergej Girman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Retinal Degeneration ◽  
Human Central Nervous System

scholarly journals Overexpression of MiR-183/96/182 Triggers Retina-Like Fate in Human Bone Marrow-Derived Mesenchymal Stem Cells (hBMSCs) in Culture

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Mohammad-Reza Mahmoudian-Sani ◽  
Fatemeh Forouzanfar ◽  
Samira Asgharzade ◽  
Nilufar Ghorbani
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Retinal Degeneration ◽  
Photoreceptor Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Efficient Treatment ◽  
Qrt Pcr

Retinal degeneration is considered as a condition ensued by different blinding disorders such as retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy, which can cause loss of photoreceptor cells and also lead to significant vision deficiencies. Although there is no efficient treatment in this domain, transplantation of stem cells has been regarded as a therapeutic approach for retinal degeneration. Thus, the purpose of this study was to analyze the potential of human bone marrow-derived mesenchymal stem cells (hBMSCs) to differentiate into photoreceptor cells via transfection of microRNA (miRNA) in vitro for regenerative medicine purposes. To this end, miR-183/96/182 cluster was transfected into hBMSCs; then, qRT-PCR was performed to measure the expression levels of miR-183/96/182 cluster and some retina-specific neuronal genes such as OTX2, NRL, PKCα, and recoverin. CRX and rhodopsin (RHO) levels were also measured through qRT-PCR and immunocytochemistry, and subsequently, cellular change morphology was detected. The findings showed no changes in the morphology of the given cells, and the expression of the neuroretinal genes such as OTX2, NRL, and PKCα. Moreover, recoverin was upregulated upon miR-183/-96/-182 overexpression in cultured hBMSCs. Ectopic overexpression of the miR-183 cluster could further increase the expression of CRX and RHO at the messenger RNA (mRNA) and protein levels. Furthermore, the data indicated that the miR-183 cluster could serve as a crucial function in photoreceptor cell differentiation. In fact, miRNAs could be assumed as potential targets to exploit silent neuronal differentiation. Ultimately, it was suggested that in vitro overexpression of miR-183 cluster could trigger reprogramming of the hBMSCs to retinal neuron fate, especially photoreceptor cells.

scholarly journals Identification of CD34+/PGDFRα+ Valve Interstitial Cells (VICs) in Human Aortic Valves: Association of Their Abundance, Morphology and Spatial Organization with Early Calcific Remodeling

2020 ◽  
Vol 21 (17) ◽  
pp. 6330
Author(s):  
Grzegorz J. Lis ◽  
Andrzej Dubrowski ◽  
Maciej Lis ◽  
Bernard Solewski ◽  
Karolina Witkowska ◽  
...  
Keyword(s):  
Heart Valves ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Interstitial Cells ◽  
Dimensional Structure ◽  
Aortic Valves ◽  
Valve Interstitial Cells ◽  
Valve Tissue ◽  
Early Signs ◽  
Younger Age

Aortic valve interstitial cells (VICs) constitute a heterogeneous population involved in the maintenance of unique valvular architecture, ensuring proper hemodynamic function but also engaged in valve degeneration. Recently, cells similar to telocytes/interstitial Cajal-like cells described in various organs were found in heart valves. The aim of this study was to examine the density, distribution, and spatial organization of a VIC subset co-expressing CD34 and PDGFRα in normal aortic valves and to investigate if these cells are associated with the occurrence of early signs of valve calcific remodeling. We examined 28 human aortic valves obtained upon autopsy. General valve morphology and the early signs of degeneration were assessed histochemically. The studied VICs were identified by immunofluorescence (CD34, PDGFRα, vimentin), and their number in standardized parts and layers of the valves was evaluated. In order to show the complex three-dimensional structure of CD34+/PDGFRα+ VICs, whole-mount specimens were imaged by confocal microscopy, and subsequently rendered using the Imaris (Bitplane AG, Zürich, Switzerland) software. CD34+/PDGFRα+ VICs were found in all examined valves, showing significant differences in the number, distribution within valve tissue, spatial organization, and morphology (spherical/oval without projections; numerous short projections; long, branching, occasionally moniliform projections). Such a complex morphology was associated with the younger age of the subjects, and these VICs were more frequent in the spongiosa layer of the valve. Both the number and percentage of CD34+/PDGFRα+ VICs were inversely correlated with the age of the subjects. Valves with histochemical signs of early calcification contained a lower number of CD34+/PDGFRα+ cells. They were less numerous in proximal parts of the cusps, i.e., areas prone to calcification. The results suggest that normal aortic valves contain a subpopulation of CD34+/PDGFRα+ VICs, which might be involved in the maintenance of local microenvironment resisting to pathologic remodeling. Their reduced number in older age could limit the self-regenerative properties of the valve stroma.

scholarly journals Differential localizations of and requirements for the two Drosophila ninaC kinase/myosins in photoreceptor cells.

1992 ◽  
Vol 116 (3) ◽  
pp. 683-693 ◽  
Author(s):  
J A Porter ◽  
J L Hicks ◽  
D S Williams ◽  
C Montell
Keyword(s):  
Retinal Degeneration ◽  
Photoreceptor Cells ◽  
Kinase Domain ◽  
Electron Microscopic Level ◽  
Head Region ◽  
Electron Microscopic ◽  
Myosin I ◽  
Microvillar Structure ◽  
The Difference ◽  
The Individual

The ninaC gene encodes two retinal specific proteins (p132 and p174) consisting of a protein kinase domain joined to a domain homologous to the head region of the myosin heavy chain. The putative myosin domain of p174 is linked at the COOH-terminus to a tail which has some similarities to myosin-I tails. In the current report, we demonstrate that the ninaC mutation results in light- and age-dependent retinal degeneration. We also show that ninaC flies display an electrophysiological phenotype before any discernible retinal degeneration indicating that the electrophysiological defect is the primary effect of the mutation. This suggests that ninaC has a role in phototransduction and that the retinal degeneration is a secondary effect resulting from the defect in phototransduction. To examine the requirements for the individual ninaC isoforms, mutant alleles were generated which express only p132 or p174. Elimination of p174 resulted in a ninaC phenotype as strong as the null allele; however, elimination of p132 had little if any effect. As a first step in investigating the basis for the difference in requirements for p174 and p132 we performed immuno-localization at the electron microscopic level and found that the two isoforms display different subcellular distributions in the photoreceptor cells. The p132 protein is restricted primarily to the cytoplasm and p174 to the rhabdomeres, the microvillar structure which is the site of action of many of the steps in phototransduction. This suggests that the p174 myosin-I type tail is the domain responsible for association with the rhabdomeres and that the substrate for the p174 putative kinase may be a rhabdomeric protein important in photo-transduction.

scholarly journals Arachidonic acid supplementation during gestational, lactational and post-weaning periods prevents retinal degeneration induced in a rodent model

2012 ◽  
Vol 109 (8) ◽  
pp. 1424-1432 ◽  
Author(s):  
Katsuhiko Yoshizawa ◽  
Tomo Sasaki ◽  
Maki Kuro ◽  
Norihisa Uehara ◽  
Hideho Takada ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Retinal Degeneration ◽  
Outer Nuclear Layer ◽  
Basal Diet ◽  
Photoreceptor Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Retinal Damage ◽  
Lewis Rats ◽  
Photoreceptor Layer ◽  
Central Retina

Fatty acids and their derivatives play a role in the response to retinal injury. The effects of dietary arachidonic acid (AA) supplementation on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was investigated in young Lewis rats during the gestational, lactational and post-weaning periods. Dams were fed 0·1, 0·5 or 2·0 % AA diets or a basal ( < 0·01 % AA) diet. On postnatal day 21 (at weaning), male pups received a single intraperitoneal injection of 50 mg MNU/kg or vehicle, and were fed the same diet as their mother for 7 d. Retinal apoptosis was analysed by the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick-end labelling (TUNEL) assay 24 h after the MNU treatment, and retinal morphology was examined 7 d post-MNU. Histologically, all rats that received MNU and were fed the basal and 0·1 % AA diets developed retinal degeneration characterised by the loss of photoreceptor cells (disappearance of the outer nuclear layer and the photoreceptor layer) in the central retina. The 0·5 and 2·0 % AA diets rescued rats from retinal damage. Morphometrically, in parallel with the AA dose (0·5 and 2·0 % AA), the photoreceptor ratio significantly increased and the retinal damage ratio decreased in the central retina, compared with the corresponding ratios in basal diet-fed rats. In parallel with the increase in serum and retinal AA levels and the AA:DHA ratio, the apoptotic index in the central retina was dose-dependently decreased in rats fed the 0·5 and 2·0 % AA diets. In conclusion, an AA-rich diet during the gestation, lactation and post-weaning periods rescued young Lewis rats from MNU-induced retinal degeneration via the inhibition of photoreceptor apoptosis. Therefore, an AA-enriched diet in the prenatal and postnatal periods may be an important strategy to suppress the degree of photoreceptor injury in humans.

scholarly journals Drosophila retinal degeneration A gene encodes an eye-specific diacylglycerol kinase with cysteine-rich zinc-finger motifs and ankyrin repeats

1993 ◽  
Vol 90 (23) ◽  
pp. 11157-11161 ◽  
Author(s):  
I Masai ◽  
A Okazaki ◽  
T Hosoya ◽  
Y Hotta
Keyword(s):  
Retinal Degeneration ◽  
Zinc Finger ◽  
Catalytic Domain ◽  
Gene Dosage ◽  
Diacylglycerol Kinase ◽  
Photoreceptor Cells ◽  
Dependent Manner ◽  
Missense Mutations ◽  
Morphological Studies ◽  
Zinc Finger Motifs

The Drosophila visual mutant, carrying the retinal degeneration A gene (rdgA), has photoreceptor cells that degenerate within a week after eclosion. Morphological studies suggested that this mutant harbors abnormalities in membrane turnover of the photoreceptor cells. Biochemically, the rdgA mutant lacks an eye-specific and membrane-associated diacylglycerol kinase (DGK; EC 2.7.1.107) activity in a gene-dosage-dependent manner, suggesting that rdgA gene encodes a DGK. We report the molecular cloning and characterization of a DGK gene, which maps to the rdgA locus. This gene, designated as DGK2, has a single open reading frame that encodes 1454 amino acids. Like porcine DGK, DGK2 has two cysteine-rich zinc-finger motifs as well as a DGK catalytic domain. The DGK2 protein contains four ankyrin-like repeats at the C-terminal region, suggesting that DGK2 is likely anchored to the membrane or cytoskeleton. Northern blot analysis and tissue in situ hybridization to adult sections revealed that DGK2 is expressed exclusively in the adult retina and that the amount of its mRNA is reduced in some of the rdgA mutant alleles. Furthermore, in two rdgA alleles, rdgA1 and rdgA2, nonsense and missense mutations occur within their DGK2 gene, respectively. Thus, we conclude that rdgA encodes an eye-specific DGK, the absence of which leads to rhabdomere degeneration due to defective phospholipid turnover.

Analysis of the treatment of basilar skull fractures with and without antibiotics

1975 ◽  
Vol 43 (6) ◽  
pp. 721-726 ◽  
Author(s):  
Ronald J. Ignelzi ◽  
Gary D. VanderArk
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rational Approach ◽  
Skull Fractures ◽  
Central Nervous System Infections ◽  
Content Type ◽  
Early Signs ◽  
Close Observation ◽  
Fine Print

✓ The efficacy of chemoprophylaxis in the treatment of basilar skull fractures was studied in 129 patients over a 2-year period; antibiotics were found ineffective in preventing central nervous system infections, and in some cases may have proved harmful. It is suggested that a more rational approach to the treatment of basilar skull fractures includes close observation of the patient for early signs of meningitis, and if these should develop, treatment with antibiotics appropriate to the organism involved.

scholarly journals Mathematical Models of Retinitis Pigmentosa: The Trophic Factor Hypothesis

2021 ◽  
Author(s):  
Paul A. Roberts
Keyword(s):  
Retinitis Pigmentosa ◽  
Mathematical Models ◽  
Retinal Degeneration ◽  
Reaction Diffusion ◽  
Temporal Patterns ◽  
Photoreceptor Cells ◽  
Trophic Factor ◽  
Cone Dystrophy ◽  
Treatment Rate ◽  
Spatio Temporal

AbstractRetinitis pigmentosa (RP) is the term used to denote a group of inherited retinal-degenerative conditions that cause progressive sight loss. Individuals with this condition lose their light-sensitive photoreceptor cells, known as rods and cones, over a period of years to decades; degeneration starting in the retinal periphery, and spreading peripherally and centrally over time. RP is a rod-cone dystrophy, meaning that rod health and function are affected earlier and more severely than that of cones. Rods degenerate due to an underlying mutation, whereas the reasons for cone degeneration are unknown. A number of mechanisms have been proposed to explain secondary cone loss and the spatio-temporal patterns of retinal degeneration in RP. One of the most promising is the trophic factor hypothesis, which suggests that rods produce a factor necessary for cone survival, such that, when rods degenerate, cone degeneration follows. In this paper we formulate and analyse mathematical models of RP under the trophic factor hypothesis. These models are constructed as systems of reaction-diffusion partial differential equations in one spatial dimension, and are solved and analysed using a combination of numerical and analytical methods. We predict the conditions under which cones will degenerate following the loss of a patch of rods from the retina, the critical trophic factor treatment rate required to prevent cone degeneration following rod loss and the spatio-temporal patterns of cone loss that would result if the trophic factor mechanism alone were responsible for retinal degeneration.

Sign in / Sign up

Export Citation Format

Share Document