scholarly journals Erratum: Corrigendum: The bacterial toxin CNF1 as a tool to induce retinal degeneration reminiscent of retinitis pigmentosa

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Viviana Guadagni ◽  
Chiara Cerri ◽  
Ilaria Piano ◽  
Elena Novelli ◽  
Claudia Gargini ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Bacterial Toxin

scholarly journals The bacterial toxin CNF1 as a tool to induce retinal degeneration reminiscent of retinitis pigmentosa

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Viviana Guadagni ◽  
Chiara Cerri ◽  
Ilaria Piano ◽  
Elena Novelli ◽  
Claudia Gargini ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Rho Gtpase ◽  
Bacterial Toxin ◽  
Postnatal Life ◽  
Rodent Models ◽  
Photoreceptor Degeneration ◽  
Large Animals ◽  
Surgical Treatments ◽  
Cytotoxic Necrotizing Factor 1

Abstract Retinitis pigmentosa (RP) comprises a group of inherited pathologies characterized by progressive photoreceptor degeneration. In rodent models of RP, expression of defective genes and retinal degeneration usually manifest during the first weeks of postnatal life, making it difficult to distinguish consequences of primary genetic defects from abnormalities in retinal development. Moreover, mouse eyes are small and not always adequate to test pharmacological and surgical treatments. An inducible paradigm of retinal degeneration potentially extensible to large animals is therefore desirable. Starting from the serendipitous observation that intraocular injections of a Rho GTPase activator, the bacterial toxin Cytotoxic Necrotizing Factor 1 (CNF1), lead to retinal degeneration, we implemented an inducible model recapitulating most of the key features of Retinitis Pigmentosa. The model also unmasks an intrinsic vulnerability of photoreceptors to the mechanism of CNF1 action, indicating still unexplored molecular pathways potentially leading to the death of these cells in inherited forms of retinal degeneration.

Short-term high-fat feeding exacerbates degeneration in retinitis pigmentosa by promoting retinal oxidative stress and inflammation

2021 ◽  
Vol 118 (43) ◽  
pp. e2100566118
Author(s):  
Oksana Kutsyr ◽  
Agustina Noailles ◽  
Natalia Martínez-Gil ◽  
Lucía Maestre-Carballa ◽  
Manuel Martinez-Garcia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Gut Microbiome ◽  
Cell Activation ◽  
High Fat ◽  
Short Term ◽  
Oxidative Markers ◽  
Degenerative Disorders ◽  
Inflammatory State

A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystrophic retinal degeneration 10 (rd10) mice, a model of retinitis pigmentosa, fed an HFD for 2 to 3 wk. Short-term HFD feeding impaired retinal responsiveness and visual acuity and enhanced photoreceptor degeneration, microglial cell activation, and Müller cell gliosis. HFD consumption also triggered the expression of inflammatory and oxidative markers in rd10 retinas. Finally, an HFD caused gut microbiome dysbiosis, increasing the abundance of potentially proinflammatory bacteria. Thus, HFD feeding drives the pathological processes of retinal degeneration by promoting oxidative stress and activating inflammatory-related pathways. Our findings suggest that consumption of an HFD could accelerate the progression of the disease in patients with retinal degenerative disorders.

scholarly journals Microglia dynamics in retinitis pigmentosa model: formation of fundus whitening and autofluorescence as an indicator of activity of retinal degeneration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenichi Makabe ◽  
Sunao Sugita ◽  
Michiko Mandai ◽  
Yoko Futatsugi ◽  
Masayo Takahashi
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Outer Nuclear Layer ◽  
Fundus Autofluorescence ◽  
Fundus Photography ◽  
Photoreceptor Outer Segments ◽  
Diagnostic Interpretation ◽  
Model Formation ◽  
Thinning Rate

Abstract In patients with retinitis pigmentosa (RP), color fundus photography and fundus autofluorescence (FAF) have been used to estimate the disease progression. To understand the origin and the diagnostic interpretation of the fundus color and FAF, we performed in vivo imaging of fundus color and FAF together with histological analyses of the retinal degeneration process using the RP model mice, rd10. FAF partly represented the accumulation of microglia in the photoreceptor outer segments. Fundus whitening suggested the presence of apoptotic cells, which spatiotemporally preceded increase in FAF. We observed two patterns of FAF localization, arcuate and diffuse, each indicating different pattern of apoptosis, wavy and diffuse, respectively. Diffuse pattern of apoptosis was suppressed in dark-raised rd10 mice, in which outer nuclear layer (ONL) loss was significantly suppressed. The occupancy of FAF correlated with the thinning rate of the ONL. Fractalkine, a microglia chemotactic factor, was detected in apoptotic photoreceptors, suggesting chemokine-induced recruitment of microglia into the ONL, which paralleled with accelerated ONL loss and increased FAF occupancy. Thus, we propose that the degree of photoreceptor apoptosis and the rate of ONL thinning in RP patients might be read from the fundus color and the FAF.

scholarly journals ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eun-Jin Lee ◽  
Priscilla Chan ◽  
Leon Chea ◽  
Kyle Kim ◽  
Randal J. Kaufman ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Mrna Levels ◽  
Photoreceptor Layer ◽  
Protein Levels ◽  
Unfolded Protein ◽  
Activating Transcription Factor ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractRetinitis Pigmentosa (RP) is a blinding disease that arises from loss of rods and subsequently cones. The P23H rhodopsin knock-in (P23H-KI) mouse develops retinal degeneration that mirrors RP phenotype in patients carrying the orthologous variant. Previously, we found that the P23H rhodopsin protein was degraded in P23H-KI retinas, and the Unfolded Protein Response (UPR) promoted P23H rhodopsin degradation in heterologous cells in vitro. Here, we investigated the role of a UPR regulator gene, activating transcription factor 6 (Atf6), in rhodopsin protein homeostasis in heterozygous P23H rhodopsin (Rho+/P23H) mice. Significantly increased rhodopsin protein levels were found in Atf6−/−Rho+/P23H retinas compared to Atf6+/−Rho+/P23H retinas at early ages (~ P12), while rhodopsin mRNA levels were not different. The IRE1 pathway of the UPR was hyper-activated in young Atf6−/−Rho+/P23H retinas, and photoreceptor layer thickness was unchanged at this early age in Rho+/P23H mice lacking Atf6. By contrast, older Atf6−/−Rho+/P23H mice developed significantly increased retinal degeneration in comparison to Atf6+/−Rho+/P23H mice in all retinal layers, accompanied by reduced rhodopsin protein levels. Our findings demonstrate that Atf6 is required for efficient clearance of rhodopsin protein in rod photoreceptors expressing P23H rhodopsin, and that loss of Atf6 ultimately accelerates retinal degeneration in P23H-KI mice.

Apoptosis, retinitis pigmentosa, and degeneration

1994 ◽  
Vol 72 (11-12) ◽  
pp. 489-498 ◽  
Author(s):  
Paul Wong
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Photoreceptor Cell ◽  
Retinal Cell ◽  
Current Evidence ◽  
Cell Degeneration ◽  
Genetic Lesion ◽  
Common Causes ◽  
Active Cell Death

The mechanism of photoreceptor cell death in different inherited retinal degenerations is not fully understood. Mutations in a number of different genes (such as rhodopsin, the beta subunit of cGMP phosphodiesterase, and peripherin) have been identified as the primary genetic lesion in different forms of human retinitis pigmentosa, one of the most common causes of inherited blindness. In all cases the manifestation of the disorder regardless of the specific primary genetic lesion is similar, resulting in photoreceptor cell degeneration and blindness. A recent hypothesis is that the active photoreceptor cell death, which is characteristic of these genetically distinct disorders, is mediated by a common induction of apoptosis. In the present review, the current evidence for active cell death during retinal cell death in several different rodent models of retinitis pigmentosa and retinal degeneration is examined.Key words: retinal degeneration, apoptosis, retinitis pigmentosa, clusterin, DNA fragmentation.

scholarly journals Dysmorphic Photoreceptors in a P23H Mutant Rhodopsin Model of Retinitis Pigmentosa Are Metabolically Active and Capable of Regenerating to Reverse Retinal Degeneration

2012 ◽  
Vol 32 (6) ◽  
pp. 2121-2128 ◽  
Author(s):  
D. C. Lee ◽  
F. R. Vazquez-Chona ◽  
W. D. Ferrell ◽  
B. M. Tam ◽  
B. W. Jones ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration
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