Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa

1998 ◽  
Vol 4 (8) ◽  
pp. 967-971 ◽  
Author(s):  
Alfred S. Lewin ◽  
Kimberly A. Drenser ◽  
William W. Hauswirth ◽  
Shimpei Nishikawa ◽  
Douglas Yasumura ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Rat Model ◽  
Autosomal Dominant ◽  
Photoreceptor Cells ◽  
Transgenic Rat ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Transgenic Rat Model

scholarly journals Erratum: Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa

10.1038/2077 ◽  
1998 ◽  
Vol 4 (9) ◽  
pp. 1081-1081 ◽  
Author(s):  
Alfred Lewin ◽  
Kimberly Drenser ◽  
William Hauswirth ◽  
Shimpei Nishikawa ◽  
Douglas Yasumura ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Rat Model ◽  
Autosomal Dominant ◽  
Photoreceptor Cells ◽  
Transgenic Rat ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Transgenic Rat Model

scholarly journals In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa

2016 ◽  
Vol 24 (3) ◽  
pp. 556-563 ◽  
Author(s):  
Benjamin Bakondi ◽  
Wenjian Lv ◽  
Bin Lu ◽  
Melissa K Jones ◽  
Yuchun Tsai ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Rat Model ◽  
Gene Editing ◽  
Autosomal Dominant ◽  
Retinal Dystrophy ◽  
Autosomal Dominant Retinitis Pigmentosa

scholarly journals Binocular Benefit Following Monocular Subretinal AAV Injection in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa (adRP)

2021 ◽  
Author(s):  
Chulbul M Ahmed ◽  
Michael T Massengill ◽  
Cristhian J Ildefonso ◽  
Ping Zhu ◽  
Hong Li ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Photoreceptor Cells ◽  
Pcr Analysis ◽  
Western Blots ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Retinal Structure ◽  
Rho Mutation ◽  
And Function ◽  
Sd Oct

Autosomal dominant retinitis pigmentosa (adRP) is frequently caused by mutations in RHO, the gene for rhodopsin. In previous experiments in dogs with the T4R mutation in RHO, an AAV2/5 vector expressing both an shRNA directed to human and dog RHO mRNA and an shRNA-resistant human RHO cDNA (AAV-RHO820-shRNA820) prevented retinal degeneration for more than 8 months following injection. To confirm that this same vector could protect the retinas of a different species and bearing a different RHO mutation, we injected mice transgenic for human P23H RHO at postnatal day 30 in one eye. For nine months, we monitored their retinal structure using spectral-domain optical coherence tomography (SD-OCT) and retinal function using electroretinography (ERG). We compared these to P23H RHO transgenic mice injected with AAV-GFP. Though retinas continued to thin over time, compared to control injected eyes, AAV-RHO820-shRNA820 slowed the loss of photoreceptor cells and decreased ERG amplitudes in AAV-RHO820-shRNA820 eyes during the nine-month study period. Unexpectedly, we also observed preservation of retinal structure and function in the untreated contralateral eyes of AAV-RHO820-shRNA820 treated mice. PCR analysis and western blots provided evidence that a low amount of vector from injected eyes was present in uninjected eyes.

scholarly journals A rat model for retinitis pigmentosa with rapid retinal degeneration enables drug evaluation in vivo

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Chisato Inoue ◽  
Tamaki Takeuchi ◽  
Akira Shiota ◽  
Mineo Kondo ◽  
Yuji Nshizawa
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Rat Model ◽  
Photoreceptor Cell ◽  
Photoreceptor Cells ◽  
Therapeutic Agents ◽  
Transgenic Rat ◽  
Cell Degeneration ◽  
Rat Strain

Abstract Background Although retinitis pigmentosa (RP) is most frequently studied in mouse models, rats, rabbits, and pigs are also used as animal models of RP. However, no studies have reported postnatal photoreceptor cell loss before complete development in these models. Here, we generated a transgenic rat strain, named the P347L rat, in which proline at position 347 in the rhodopsin protein was replaced with leucine. Results A pathological analysis of photoreceptor cells in the P347L rat model was performed, and drugs with potential use as therapeutic agents against RP were investigated. The data clearly showed rapid degeneration and elimination of the outer nuclear layer even before the photoreceptor cells were fully established in P347L rats. To test the usefulness of the P347L rat in the search for new therapeutic agents against RP, the effects of rapamycin on RP were investigated in this rat strain. The findings suggest that rapamycin promotes autophagy and autophagosomal uptake of the rhodopsin that has accumulated abnormally in the cytoplasm, thereby alleviating stress and delaying photoreceptor cell death. Conclusions In this RP model, the time to onset of retinal degeneration was less than that of previously reported RP models with other rhodopsin mutations, enabling quicker in vivo evaluation of drug efficacy. Administration of rapamycin delayed the photoreceptor cell degeneration by approximately 1 day.

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