scholarly journals Optimization of In Vivo Confocal Autofluorescence Imaging of the Ocular Fundus in Mice and Its Application to Models of Human Retinal Degeneration

2012 ◽  
Vol 53 (2) ◽  
pp. 1066 ◽  
Author(s):  
Peter Charbel Issa ◽  
Mandeep S. Singh ◽  
Daniel M. Lipinski ◽  
Ngaihang V. Chong ◽  
François C. Delori ◽  
...  
2018 ◽  
Vol 10 (465) ◽  
pp. eaap8677 ◽  
Author(s):  
Chenchen Niu ◽  
Thazah P. Prakash ◽  
Aneeza Kim ◽  
John L. Quach ◽  
Laryssa A. Huryn ◽  
...  

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by cerebellar and retinal degeneration, and is caused by a CAG-polyglutamine repeat expansion in the ATAXIN-7 gene. Patients with SCA7 develop progressive cone-rod dystrophy, typically resulting in blindness. Antisense oligonucleotides (ASOs) are single-stranded chemically modified nucleic acids designed to mediate the destruction, prevent the translation, or modify the processing of targeted RNAs. Here, we evaluated ASOs as treatments for SCA7 retinal degeneration in representative mouse models of the disease after injection into the vitreous humor of the eye. Using Ataxin-7 aggregation, visual function, retinal histopathology, gene expression, and epigenetic dysregulation as outcome measures, we found that ASO-mediated Ataxin-7 knockdown yielded improvements in treated SCA7 mice. In SCA7 mice with retinal disease, intravitreal injection of Ataxin-7 ASOs also improved visual function despite initiating treatment after symptom onset. Using color fundus photography and autofluorescence imaging, we also determined the nature of retinal degeneration in human SCA7 patients. We observed variable disease severity and cataloged rapidly progressive retinal degeneration. Given the accessibility of neural retina, availability of objective, quantitative readouts for monitoring therapeutic response, and the rapid disease progression in SCA7, ASOs targeting ATAXIN-7 might represent a viable treatment for SCA7 retinal degeneration.


2015 ◽  
Vol 56 (4) ◽  
pp. 2423 ◽  
Author(s):  
Hammurabi Bartuma ◽  
Sandra Petrus-Reurer ◽  
Monica Aronsson ◽  
Sofie Westman ◽  
Helder André ◽  
...  

2019 ◽  
Vol 137 (6) ◽  
pp. 603 ◽  
Author(s):  
Hongxin Song ◽  
Ethan A. Rossi ◽  
Qiang Yang ◽  
Charles E. Granger ◽  
Lisa R. Latchney ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenichi Makabe ◽  
Sunao Sugita ◽  
Michiko Mandai ◽  
Yoko Futatsugi ◽  
Masayo Takahashi

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.


2006 ◽  
Vol 14 (15) ◽  
pp. 6713 ◽  
Author(s):  
Laure S. Fournier ◽  
Vincenzo Lucidi ◽  
Kirill Berejnoi ◽  
Theodore Miller ◽  
Stavros G. Demos ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Kaung Htet Aung ◽  
Hua Liu ◽  
Zongwen Ke ◽  
Shuang Jiang ◽  
Jianhua Huang

2009 ◽  
Vol 14 (2) ◽  
pp. 024017 ◽  
Author(s):  
Xiao Han ◽  
Harvey Lui ◽  
David I. McLean ◽  
Haishan Zeng

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