AAV-mediated lysophosphatidylcholine acyltransferase 1 (Lpcat1) gene replacement therapy rescues retinal degeneration in rd11 mice.

@article{Dai2014AAVmediatedLA,
  title={AAV-mediated lysophosphatidylcholine acyltransferase 1 (Lpcat1) gene replacement therapy rescues retinal degeneration in rd11 mice.},
  author={Xufeng Dai and Juanjuan Han and Yan Qi and Hua Zhang and Lue Xiang and Jineng Lv and Jie Li and Wen-tao Deng and Bo Chang and William W. Hauswirth and Ji-Jing Pang},
  journal={Investigative ophthalmology \& visual science},
  year={2014},
  volume={55 3},
  pages={
          1724-34
        }
}
PURPOSE The retinal degeneration 11 (rd11) mouse is a newly discovered, naturally occurring animal model with early photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration. The rd11 mice carry a spontaneous mutation in the lysophosphatidylcholine acyltransferase 1 (Lpcat1) gene. Here, we evaluate whether gene replacement therapy using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can arrest retinal degeneration and restore retinal function in this… Expand
Effects of Subretinal Gene Transfer at Different Time Points in a Mouse Model of Retinal Degeneration
TLDR
It is found that gene therapy was more effective against RD when exposure to light was limited before and after treatment, and long-term preservation of electroretinogram responses, and preservation of retinal structure is observed, indicating that early treatment followed by limited light exposure can improve gene therapy effectiveness for the eyes of rd11 mice. Expand
Intraperitoneal chromophore injections delay early-onset and rapid retinal cone degeneration in a mouse model of Leber congenital amaurosis.
  • Xufeng Dai, Xumin Jin, +5 authors Hao Chen
  • Medicine
  • Experimental eye research
  • 2021
TLDR
The findings suggest that early 11cRAL treatment is useful for restoring retinal function and rescuing morphology in the rd12 mouse model, and the early-onset and rapid cone degeneration can be delayed before gene therapy. Expand
Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells
TLDR
The results suggest that the LPCAT1-dependent production of saturated PC is critical for metabolic adaptation during photoreceptor maturation, and highlights the therapeutic potential of saturated fatty acid metabolism in photorecept cell degeneration-related retinal diseases. Expand
The Degeneration and Apoptosis Patterns of Cone Photoreceptors in rd11 Mice
TLDR
The key genes associated with apoptosis indicated that the degeneration and apoptosis of cone photoreceptors began at P14 of rd11 mice, which was a key point for gene therapy. Expand
Molecular screening of the LPCAT1 gene in patients with retinitis pigmentosa without defined mutations in known retinitis pigmentosa genes.
TLDR
No disease‑causing mutations in the LPCAT1 gene were identified, indicating that L PCAT1 either does not confer a genetic predisposition to RP, or that the incidence of mutations in LPCat1 is particularly rare in patients with RP. Expand
Long-term retinal cone rescue using a capsid mutant AAV8 vector in a mouse model of CNGA3-achromatopsia
TLDR
AAV8 with capsid Y-F and T-V mutations may be one of the most effective AAV vectors for long-term treatment in a naturally occurring mouse model of CNGA3 achromatopsia. Expand
CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING
TLDR
Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations, and high diagnostic yields are obtained. Expand
The Frequency-Response Electroretinogram Distinguishes Cone and Abnormal Rod Function in rd12 Mice
TLDR
It is shown, for the first time, that frequency-response ERGs can effectively distinguish cone- and rod-driven responses in the rd12 mouse, and is another simple and valid method for evaluating the respective contributions of retinal rods and cones. Expand
Intravenous injection of l‐aspartic acid &bgr;‐hydroxamate attenuates choroidal neovascularization via anti‐VEGF and anti‐inflammation
TLDR
It is identified that intravenous injection of L‐ABH significantly attenuates CNV by laser injury without negative effect on retinal function and visual behavior. Expand
A Novel In Vivo Model of Focal Light Emitting Diode-Induced Cone-Photoreceptor Phototoxicity: Neuroprotection Afforded by Brimonidine, BDNF, PEDF or bFGF
TLDR
It is concluded that LIP results in rod and cone-Photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 34 REFERENCES
Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice
TLDR
It is shown that the rd11 mouse mutant and its allelic strain, B6-JR2845, exhibit rapid photoreceptor dysfunction, followed by degeneration of both rods and cones, adding another dimension to an essential role for LPCAT1 in retinalPhotoreceptor homeostasis. Expand
AAV-mediated gene therapy for retinal degeneration in the rd10 mouse containing a recessive PDEbeta mutation.
TLDR
These data demonstrate that P14 administration of AAV5-smCBA-PDEbeta can prevent retinal degeneration in rd10 mice, as reflected by significant structural, biochemical, electrophysiological, and behavioral preservation/restoration. Expand
Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse, a model of recessive retinitis pigmentosa.
  • J. Pang, X. Dai, +12 authors W. Hauswirth
  • Biology, Medicine
  • Molecular therapy : the journal of the American Society of Gene Therapy
  • 2011
TLDR
It is suggested that tyrosine-capsid mutant AAV vectors may be effective for treating other rapidly degenerating models of retinal degeneration and the first demonstration of long-term phenotypic rescue by gene therapy in an animal model of PDEβ-RP. Expand
Adenoviral-mediated gene transfer to retinal explants during development and degeneration.
TLDR
Retinal explants provide a rapid, efficient method to compare the transduction efficiency of adenoviral vector-mediated reporter gene delivery at different ages in normal and rd mice, and suggest efficient adenOVirus-mediated gene transfer is more attainable in developing or degenerating retina. Expand
Gene therapy rescues cone structure and function in the 3-month-old rd12 mouse: a model for midcourse RPE65 leber congenital amaurosis.
TLDR
The results support and extend those of the previous study that gene therapy can stop early cone degeneration, and provide proof that delayed treatment can restore the function and morphology of the remaining cones. Expand
AAV-mediated gene replacement, either alone or in combination with physical and pharmacological agents, results in partial and transient protection from photoreceptor degeneration associated with betaPDE deficiency.
TLDR
More efficient gene transfer tools than those used in this study should be explored to increase the effect of gene replacement and to design gene-based strategies that block the apoptotic pathways activated by βPDE deficiency. Expand
Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of RPE65 Leber congenital amaurosis.
  • J. Pang, B. Chang, +15 authors W. Hauswirth
  • Biology, Medicine
  • Molecular therapy : the journal of the American Society of Gene Therapy
  • 2006
TLDR
It is shown that gene therapy can restore normal vision-dependent behavior in a congenitally blind animal and all parameters of restored retinal health remained stable for at least 7 months. Expand
Self-complementary AAV-mediated gene therapy restores cone function and prevents cone degeneration in two models of Rpe65 deficiency
TLDR
It is established that a self-complimentary AAV5 vector can restore substantial visual function in two genetically distinct models of Rpe65 deficiency within 4 days of treatment, supporting continuation of current Leber's congenital amaurosis-2 clinical trials with an added emphasis on cone subtype analysis and early intervention. Expand
AAV-mediated gene therapy in mouse models of recessive retinal degeneration.
TLDR
This review focuses on the AAV-based gene therapy in mouse models of recessive retinal degenerations, especially those in which delivery of the correct copy of the wild-type gene has led to significant beneficial effects on visual function, as determined by morphological, biochemical, electroretinographic and behavioral analysis. Expand
Enhanced gene delivery to the neonatal retina through systemic administration of tyrosine-mutated AAV9
TLDR
Results show that a novel, double tyrosine mutant of AAV9 significantly enhanced gene delivery to the CNS and retina, and that gene expression can be restricted to rod photoreceptor cells by incorporating a rhodopsin promoter. Expand
...
1
2
3
4
...