Role of the pigment epithelium in inherited retinal degeneration analyzed with experimental mouse chimeras

1976 ◽  
Vol 23 (2) ◽  
pp. 227-245 ◽  
Author(s):  
Matthew M. LaVail ◽  
Richard J. Mullen
Keyword(s):  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Mouse Chimeras ◽  
Experimental Mouse ◽  
Inherited Retinal Degeneration

scholarly journals Ccr2 suppression by minocycline in Cx3cr1/Ccr2-visualized inherited retinal degeneration

2020 ◽  
Author(s):  
Ryo Terauchi ◽  
Hideo Kohno ◽  
Sumiko Watanabe ◽  
Saburo Saito ◽  
Akira Watanabe ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Expression Pattern ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Rescue Effect ◽  
Ccr2 Expression ◽  
Retinal Inflammation ◽  
Inherited Retinal Degeneration ◽  
Old Mice ◽  
Cx3cr1 Expression

AbstractRetinal inflammation accelerates photoreceptor cell death (PCD) caused by retinal degeneration. Minocycline, a semisynthetic broad-spectrum tetracycline antibiotic, has previously been reported to show PCD rescue effect in retinal degeneration. The purpose of this study was to assess the effect of minocycline on Cx3cr1 and Ccr2 expression in retinal degeneration. Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice, which enabled observation of Cx3cr1- and Ccr2-expression pattern in inherited retinal degeneration, were used to test the effect of minocycline. Minocycline was systemically administered to Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice. For observing the effect of minocycline on Cx3cr1 and Ccr2 expression, administration was started on 4-week-old mice and continued for 2 weeks. To assess the PCD rescue effect, minocycline was administered to 6-week-old mice for 2 weeks. The expression pattern of Cx3cr1-GFP and Ccr2-RFP were observed on retinal and retinal pigment epithelium (RPE) flat-mounts. The severity of retinal degeneration was assessed on retinal sections. Minocycline administration suppressed Ccr2 expression in Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice as observed in retinal and RPE flat-mounts. On the contrary, Cx3cr1 expression was not affected by minocycline administration. Retinal degeneration is ameliorated in minocycline administered Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice. In conclusions, Minocycline suppression of Ccr2 expression correlates to amelioration of retinal degeneration.

scholarly journals Study of the functional integrity of the retinal pigment epithelium with a new technique in two models of inherited retinal degeneration

2019 ◽  
Vol 97 (S263) ◽  
Author(s):  
Johnny Di Pierdomenico ◽  
Francisco Javier Valiente Soriano ◽  
Manuel Salinas Navarro ◽  
Diego García‐Ayuso ◽  
María Paz Villegas‐Pérez ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
New Technique ◽  
Functional Integrity ◽  
A New Technique ◽  
Inherited Retinal Degeneration

scholarly journals Role of Translational Attenuation in Inherited Retinal Degeneration

2019 ◽  
Vol 60 (14) ◽  
pp. 4849 ◽  
Author(s):  
Christopher R. Starr ◽  
Cyril N. A. Nyankerh ◽  
Xiaoping Qi ◽  
Yang Hu ◽  
Oleg S. Gorbatyuk ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Inherited Retinal Degeneration

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.

Assessment of inner retinal oxygen metrics and thickness in a mouse model of inherited retinal degeneration

2021 ◽  
Vol 205 ◽  
pp. 108480
Author(s):  
Mansour Rahimi ◽  
Sophie Leahy ◽  
Nathanael Matei ◽  
Norman P. Blair ◽  
Shinwu Jeong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinal Degeneration ◽  
Inherited Retinal Degeneration

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.

scholarly journals The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies

2021 ◽  
Vol 22 (13) ◽  
pp. 6975
Author(s):  
Burcin Özdirik ◽  
Tobias Müller ◽  
Alexander Wree ◽  
Frank Tacke ◽  
Michael Sigal
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Gut Microbiome ◽  
Sclerosing Cholangitis ◽  
Functional Characterization ◽  
Significant Risk ◽  
Pharmacological Agents ◽  
Experimental Mouse ◽  
Biliary Malignancies ◽  
End Stage

Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.

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