UMMS Affiliation

Department of Ophthalmology and Visual Sciences; Horae Gene Therapy Center; Department of Microbiology and Physiological Systems; NeuroNexus Institute

Publication Date

2021-09-02

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Eye Diseases | Nervous System Diseases | Neuroscience and Neurobiology | Ophthalmology

Abstract

Purpose: Oxidative stress is a major factor underlying many neurodegenerative diseases. However, antioxidant therapy has had mixed results, possibly because of its indiscriminate activity. The purpose of our study was to determine if the human OXR1 (hOXR1) antioxidant regulatory gene could protect neurons from oxidative stress and delay photoreceptor cell death.

Methods: The cone-like 661W cell line was transfected to stably express the hOXR1 gene. Oxidative stress was induced by the addition of hydrogen peroxide (H2O2). Intracellular levels of reactive oxygen species (ROS), caspase cleavage, and cellular resistance to oxidative stress were determined and compared between the control and hOXR1 cells. For in vivo analysis, AAV8-hOXR1 was injected subretinally into the rd1 mouse model of retinal degeneration. Functional and structural integrity of the photoreceptors were assessed using electroretinography (ERG), histology, and immunofluorescence analysis.

Results: Expression of hOXR1 increased cellular resistance and reduced ROS levels and caspase cleavage in the 661W cell line after H2O2-induced oxidative stress. Subretinal injection of AAV8-hOXR1 in the rd1 mice improved their photoreceptor light response, expression and localization of photoreceptor-specific proteins, and delayed retinal degeneration.

Conclusions: Our results suggest that OXR1 is a potential therapy candidate for retinal degeneration. Because OXR1 targets oxidative stress, a common feature of many retinal degenerative diseases, it should be of therapeutic value to multiple retinal degenerative diseases.

Keywords

oxidative stress, gene therapy, retinal degeneration

Rights and Permissions

Copyright 2021 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

DOI of Published Version

10.1167/iovs.62.12.8

Source

Sahu B, Leon LM, Zhang W, Puranik N, Periasamy R, Khanna H, Volkert M. Oxidative Stress Resistance 1 Gene Therapy Retards Neurodegeneration in the rd1 Mutant Mouse Model of Retinopathy. Invest Ophthalmol Vis Sci. 2021 Sep 2;62(12):8. doi: 10.1167/iovs.62.12.8. PMID: 34505865; PMCID: PMC8434758. Link to article on publisher's site

Journal/Book/Conference Title

Investigative ophthalmology and visual science

Related Resources

Link to Article in PubMed

PubMed ID

34505865

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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