scholarly journals The role of the tissue environment in the expression of spotting genes in the mouse

Development ◽  
1973 ◽  
Vol 30 (2) ◽  
pp. 483-490
Author(s):  
M. S. Deol
Keyword(s):  
Normal Tissue ◽  
Direct Evidence ◽  
Retinal Pigment ◽  
Gene Activity ◽  
Pigment Cells ◽  
Dominant Spotting

Genes causing white spotting in the mouse act in two major ways: some affect the melanoblasts, while others affect the tissue environment of the melanoblasts. The question is whether the normal tissue environment plays any role in the origin of spots in those mutants in which the melanoblasts are believed to be the site of gene activity. An earlier study, using the genotypes +/mi, Miwh/+, s/s, Wυ/+ and Wυ/Wυ (mi = microphthalmia; Miwh = white; s = piebald; Wr = viable dominant spotting), indicated that it probably does, the evidence largely consisting in the occurrence of extremely precise pigmentation patterns on a minute scale. It seemed that more direct evidence could be obtained by comparing the pigmentation of the iris with that of the choroid and the retina in the same eye in these and other genotypes. The outer and inner layers of the iris derive their pigment cells from the choroid and the retina respectively; therefore any clear and consistent differences between the behaviour of these cells in their original and their secondary place of activity would constitute evidence for the role of the tissue environment. Such differences were found. It was also found that in another genotype, Miwh/mi, the retinal pigment cells, although unpigmented, are clearly distinguishable. This casts serious doubt on the widespread assumption that melanoblasts which do not differentiate always die.

scholarly journals Modulation of crayfish retinal function by red pigment concentrating hormone

1995 ◽  
Vol 198 (7) ◽  
pp. 1447-1454 ◽  
Author(s):  
A Garfias ◽  
L Rodríguez-Sosa ◽  
H Aréchiga
Keyword(s):  
Circadian Rhythm ◽  
Light Adaptation ◽  
Retinal Pigment ◽  
Physiological Role ◽  
Pigment Cells ◽  
Red Pigment ◽  
Retinal Activity ◽  
Retinal Photoreceptors ◽  
Dose Dependent

The role of the crustacean octapeptide red pigment concentrating hormone (RPCH) in the control of crayfish retinal activity was explored. RPCH injection into intact animals resulted, after a latency of 10­30 min, in a dose-dependent enhancement of electroretinogram (ERG) amplitude lasting 60­120 min. RPCH was able to potentiate ERG amplitude in both light-adapted and dark-adapted animals. Following light-adaptation, responsiveness to RPCH was five times higher than following dark-adaptation. In conjunction with ERG enhancement, in light-adapted animals, RPCH injection elicited a dose-dependent retraction of distal retinal pigment, but did not affect proximal retinal pigment position. The effects of RPCH were blocked by a polyclonal antibody raised against a tyrosinated form of RPCH (A-tyr-RPCH). The antibody was also capable of partially blocking the nocturnal phase of the circadian rhythm of ERG amplitude and the darkness-induced retraction of distal retinal pigment. These results suggest that RPCH acts both on the retinal photoreceptors and on the distal pigment cells, playing a physiological role as a mediator of the effects induced by darkness and by the nocturnal phase of the circadian rhythm.

The photoreceptor cytoskeleton visualized

1992 ◽  
Vol 50 (1) ◽  
pp. 480-481
Author(s):  
Beth Burnside
Keyword(s):  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Polarization ◽  
Synaptic Proteins ◽  
Cell Functions ◽  
Vertebrate Photoreceptor ◽  
Numerous Cell ◽  
Turn Over

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

Direct Evidence for the Role of Inhibition in Resolving Interference

2009 ◽  
Author(s):  
M. Karl Healey ◽  
Karen L. Campbell ◽  
Lynn Hasher ◽  
Lynn Ossher
Keyword(s):  
Direct Evidence

scholarly journals CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 ◽  
Vol 19 (1) ◽  
pp. 495-504 ◽  
Author(s):  
John Sok ◽  
Xiao-Zhong Wang ◽  
Nikoleta Batchvarova ◽  
Masahiko Kuroda ◽  
Heather Harding ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Target Gene ◽  
Target Genes ◽  
Direct Evidence ◽  
Nuclear Protein ◽  
Intracellular Form ◽  
Carbonic Anhydrase Vi ◽  
Responsive Element

ABSTRACT CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducibleCA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VIexpression in c/ebpβ−/− cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

scholarly journals Stoichiometric Analysis of Shifting in Subcellular Compartmentalization of HSP70 within Ischemic Penumbra

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3578
Author(s):  
Federica Mastroiacovo ◽  
Francesca Biagioni ◽  
Paola Lenzi ◽  
Larisa Ryskalin ◽  
Stefano Puglisi-Allegra ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Neuronal Survival ◽  
Hsp 70 ◽  
Preclinical Models ◽  
Brain Areas ◽  
Cell Compartments ◽  
Control Brain ◽  
Disease Modifier ◽  
Subcellular Compartmentalization

The heat shock protein (HSP) 70 is considered the main hallmark in preclinical studies to stain the peri-infarct region defined area penumbra in preclinical models of brain ischemia. This protein is also considered as a potential disease modifier, which may improve the outcome of ischemic damage. In fact, the molecule HSP70 acts as a chaperonine being able to impact at several level the homeostasis of neurons. Despite being used routinely to stain area penumbra in light microscopy, the subcellular placement of this protein within area penumbra neurons, to our knowledge, remains undefined. This is key mostly when considering studies aimed at deciphering the functional role of this protein as a determinant of neuronal survival. The general subcellular placement of HSP70 was grossly reported in studies using confocal microscopy, although no direct visualization of this molecule at electron microscopy was carried out. The present study aims to provide a direct evidence of HSP70 within various subcellular compartments. In detail, by using ultrastructural morphometry to quantify HSP70 stoichiometrically detected by immuno-gold within specific organelles we could compare the compartmentalization of the molecule within area penumbra compared with control brain areas. The study indicates that two cell compartments in control conditions own a high density of HSP70, cytosolic vacuoles and mitochondria. In these organelles, HSP70 is present in amount exceeding several-fold the presence in the cytosol. Remarkably, within area penumbra a loss of such a specific polarization is documented. This leads to the depletion of HSP70 from mitochondria and mostly cell vacuoles. Such an effect is expected to lead to significant variations in the ability of HSP70 to exert its physiological roles. The present findings, beyond defining the neuronal compartmentalization of HSP70 within area penumbra may lead to a better comprehension of its beneficial/detrimental role in promoting neuronal survival.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals A human model of Batten disease shows role of CLN3 in phagocytosis at the photoreceptor–RPE interface

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cynthia Tang ◽  
Jimin Han ◽  
Sonal Dalvi ◽  
Kannan Manian ◽  
Lauren Winschel ◽  
...  
Keyword(s):  
Photoreceptor Cell ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Loss ◽  
Human Model ◽  
Lysosomal Storage ◽  
Rpe Cells ◽  
Cln3 Disease

AbstractMutations in CLN3 lead to photoreceptor cell loss in CLN3 disease, a lysosomal storage disorder characterized by childhood-onset vision loss, neurological impairment, and premature death. However, how CLN3 mutations cause photoreceptor cell death is not known. Here, we show that CLN3 is required for phagocytosis of photoreceptor outer segment (POS) by retinal pigment epithelium (RPE) cells, a cellular process essential for photoreceptor survival. Specifically, a proportion of CLN3 in human, mouse, and iPSC-RPE cells localized to RPE microvilli, the site of POS phagocytosis. Furthermore, patient-derived CLN3 disease iPSC-RPE cells showed decreased RPE microvilli density and reduced POS binding and ingestion. Notably, POS phagocytosis defect in CLN3 disease iPSC-RPE cells could be rescued by wild-type CLN3 gene supplementation. Altogether, these results illustrate a novel role of CLN3 in regulating POS phagocytosis and suggest a contribution of primary RPE dysfunction for photoreceptor cell loss in CLN3 disease that can be targeted by gene therapy.

scholarly journals The Role of Imaging in Planning Treatment for Central Serous Chorioretinopathy

2021 ◽  
Vol 14 (2) ◽  
pp. 105
Author(s):  
Stefano Da Pozzo ◽  
Pierluigi Iacono ◽  
Alessandro Arrigo ◽  
Maurizio Battaglia Parodi
Keyword(s):  
Central Serous Chorioretinopathy ◽  
Therapeutic Strategy ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Subretinal Fluid ◽  
Subretinal Space ◽  
Planning Treatment ◽  
Multiple Biomarkers ◽  
Effective Procedures

Central serous chorioretinopathy (CSC) is a controversial disease both in terms of clinical classification and choice of therapeutic strategy. Choroidal layers, retinal pigment epithelium (RPE), photoreceptors, and retina are involved to varying degrees. Beyond well-known symptoms raising the clinical suspect of CSC and slit-lamp fundus examination, multimodal imaging plays a key role in assessing the extent of chorioretinal structural involvement. Subretinal fluid (SRF) originating from the choroid leaks through one or multiple RPE defects and spreads into the subretinal space. Spontaneous fluid reabsorption is quite common, but in some eyes, resolution can be obtained only after treatment. Multiple therapeutic strategies are available, and extensive research identified the most effective procedures. Imaging has carved a significant role in guiding the choice of the most appropriate strategy for each single CSC eye. Multiple biomarkers have been identified, and all of them represent a diagnostic and prognostic reference point. This review aims to provide an updated and comprehensive analysis of the current scientific knowledge about the role of imaging in planning the treatment in eyes affected by CSC.

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