scholarly journals Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia

2006 ◽  
Vol 116 (2) ◽  
pp. 386-394 ◽  
Author(s):  
T. Tolmachova
Keyword(s):  
Retinal Pigment Epithelium ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Conditional Knockout ◽  
Conditional Knockout Mouse

scholarly journals Retinal Pigment Epithelium Defects Accelerate Photoreceptor Degeneration in Cell Type–Specific Knockout Mouse Models of Choroideremia

2010 ◽  
Vol 51 (10) ◽  
pp. 4913 ◽  
Author(s):  
Tanya Tolmachova ◽  
Silene T. Wavre-Shapton ◽  
Alun R. Barnard ◽  
Robert E. MacLaren ◽  
Clare E. Futter ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Degeneration ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals Easi-CRISPR for creating knock-in and conditional knockout mouse models using long ssDNA donors

2017 ◽  
Vol 13 (1) ◽  
pp. 195-215 ◽  
Author(s):  
Hiromi Miura ◽  
Rolen M Quadros ◽  
Channabasavaiah B Gurumurthy ◽  
Masato Ohtsuka
Keyword(s):  
Mouse Models ◽  
Knockout Mouse ◽  
Conditional Knockout ◽  
Conditional Knockout Mouse

scholarly journals Does murine spermatogenesis require WNT signalling? A lesson from Gpr177 conditional knockout mouse models

2016 ◽  
Vol 7 (6) ◽  
pp. e2281-e2281 ◽  
Author(s):  
Su-Ren Chen ◽  
J-X Tang ◽  
J-M Cheng ◽  
X-X Hao ◽  
Y-Q Wang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Knockout Mouse ◽  
Wnt Signalling ◽  
Conditional Knockout ◽  
Conditional Knockout Mouse

scholarly journals Ultrastructural alterations in the retinal pigment epithelium and photoreceptors of a Stargardt patient and three Stargardt mouse models: indication for the central role of RPE melanin in oxidative stress

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5215 ◽  
Author(s):  
Tatjana Taubitz ◽  
Alexander V. Tschulakow ◽  
Marina Tikhonovich ◽  
Barbara Illing ◽  
Yuan Fang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Electron Density ◽  
Mouse Models ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Superoxide Anions ◽  
Lysosomal Dysfunction ◽  
Lipofuscin Granules

Background Stargardt disease (SD) is characterized by the accumulation of the age-pigment lipofuscin in the retinal pigment epithelium (RPE) and subsequent neuroretinal degeneration. The disease leads to vision loss early in life. Here, we investigate age-dependent ultrastructural changes in three SD mouse models: albino Abca4-/- and pigmented Abca4-/- and Abca4-/-.Rdh8-/- mice. Since we found indications for oxidative stress primarily in albino SD mice, we tested RPE melanin for its antioxidative capabilities. Methods SD mouse eyes were investigated by light, fluorescence and electron microscopy and were compared to the respective albino and pigmented wild type mice and to a human donor SD eye. To confirm the role of RPE melanin in scavenging oxidative stress, melanin from S. officinalis as a standard and porcine RPE were tested for their capability to quench superoxide anions. Results Histological alterations indicative of oxidative stress and/or lysosomal dysfunction were present in albino Abca4-/- and Abca4-/-.Rdh8-/- mice. Retinal damage, such as inner segment rupture and pyknotic or free photoreceptor nuclei in the subretinal space and RPE vacuolization were exclusively found in albino Abca4-/- mice. Shortened and disorganized photoreceptor outer segments and dead RPE cells were found in albino Abca4-/- and Abca4-/-.Rdh8-/- mice, with earlier onset in albino Abca4-/- mice. Undegraded phagosomes and lipofuscin accumulation were present in the RPE of all three SD strains, but numbers were highest in Abca4-/-.Rdh8-/- mice. Lipofuscin morphology differed between SD strains: (melano-)lipofuscin granules in pigmented Abca4-/- mice had a homogenous electron density and sharp demarcations, while lipofuscin in albino Abca4-/- mice had a flocculent electron density and often lacked a surrounding membrane, indicating loss of lysosomal integrity. Young Abca4-/-.Rdh8-/- mice showed (melano-)lipofuscin granules with homogenous electron density, while in aged animals granules with flocculent electron density predominated. Both strains of pigmented SD mice had melanolipofuscin clusters as found in the human SD eye. Like melanin from S. officinalis, porcine RPE melanin can also quench superoxide anions. Discussion The presented pathologies in albino Abca4-/- and Abca4-/-.Rdh8-/- mice suggest oxidative stress and/or lysosomal dysfunction within the RPE. Since albino Abca4-/- mice have the earliest onset and severest damage and as absence of melanin and also melanin turnover with age are known to diminish RPEs anti-oxidative properties, we assume that RPE melanin plays a role in SD related damages. A lack of pathology in pigmented Abca4-/- mice due to lower stress levels as compared to the Abca4-/-.Rdh8-/- mice underlines this hypothesis. It is also supported by the finding that RPE melanin can quench superoxide anions. We therefore suppose that RPE melanin is important in retinal health and we discuss its role as an oxidative stress scavenger.

scholarly journals Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Müller glial cells

2019 ◽  
Vol 316 (1) ◽  
pp. C121-C133 ◽  
Author(s):  
Aditi Swarup ◽  
Ivy S. Samuels ◽  
Brent A. Bell ◽  
John Y. S. Han ◽  
Jianhai Du ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Pigment Epithelium ◽  
Glucose Transport ◽  
Glial Cells ◽  
Photoreceptor Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Conditional Knockout ◽  
Müller Glial Cells ◽  
Outer Segments

The retina is one of the most metabolically active tissues in the body and utilizes glucose to produce energy and intermediates required for daily renewal of photoreceptor cell outer segments. Glucose transporter 1 (GLUT1) facilitates glucose transport across outer blood retinal barrier (BRB) formed by the retinal pigment epithelium (RPE) and the inner BRB formed by the endothelium. We used conditional knockout mice to study the impact of reducing glucose transport across the RPE on photoreceptor and Müller glial cells. Transgenic mice expressing Cre recombinase under control of the Bestrophin1 ( Best1) promoter were bred with Glut1flox/flox mice to generate Tg-Best1-Cre:Glut1flox/flox mice ( RPEΔGlut1). The RPEΔGlut1 mice displayed a mosaic pattern of Cre expression within the RPE that allowed us to analyze mice with ~50% ( RPEΔGlut1m) recombination and mice with >70% ( RPEΔGlut1h) recombination separately. Deletion of GLUT1 from the RPE did not affect its carrier or barrier functions, indicating that the RPE utilizes other substrates to support its metabolic needs thereby sparing glucose for the outer retina. RPEΔGlut1m mice had normal retinal morphology, function, and no cell death; however, where GLUT1 was absent from a span of RPE greater than 100 µm, there was shortening of the photoreceptor cell outer segments. RPEΔGlut1h mice showed outer segment shortening, cell death of photoreceptors, and activation of Müller glial cells. The severe phenotype seen in RPEΔGlut1h mice indicates that glucose transport via the GLUT1 transporter in the RPE is required to meet the anabolic and catabolic requirements of photoreceptors and maintain Müller glial cells in a quiescent state.

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