Related Experiment Video
Updated: Jul 6, 2026
Organotypic Retinal Explant Cultures from Macaque Monkey
Published on: August 24, 2022
Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice
Kouhei Hashizume1, Manabu Hirasawa, Yutaka Imamura
1Department of Ophthalmology, Inaida Laboratory, Keio University School of Medicine, 35-Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Abstract:
The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase (SOD1) in mice leads to many different phenotypes that resemble accelerated aging. The purpose of this study was to examine the morphology and physiology of the sensory retina in Sod1(-/-) mice. The amplitudes of the a- and b-waves of electroretinograms elicited by stimuli of different intensity were reduced in senescent Sod1(-/-) mice, and this reduction in amplitude was more pronounced with increasing age. Retinal morphometric analyses showed a reduced number of nuclei in both the inner nuclear cell layer and outer nuclear cell layer. Electron microscopy revealed swollen cells and degenerated mitochondria in the inner nuclear cell and outer nuclear cell layer of senescent Sod1(-/-) mice indicating necrotic cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed no significant differences in the number of apoptotic cells between Sod1(-/-) and wild-type mice, and activated caspase-3 could not be detected in the retina of Sod1(-/-) mice. In addition to the age-related macular degeneration-like phenotypes previously reported, Sod1(-/-) mice also present progressive retinal degeneration. Our results indicate that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated retinal degeneration.
Insights
Mice lacking superoxide dismutase 1 (SOD1) exhibit accelerated aging phenotypes, including progressive retinal degeneration. This study reveals SOD1 deficiency causes significant vision impairment and cell death in the retina, suggesting a model for studying oxidative stress-related eye diseases.
Area of Science:
- Biochemistry
- Neuroscience
- Ophthalmology
Background:
- Superoxide dismutase (SOD) enzymes are crucial for cellular antioxidant defense.
- Cu,Zn-superoxide dismutase (SOD1) deficiency in mice results in phenotypes mimicking accelerated aging.
- Previous research linked SOD1 deficiency to age-related macular degeneration-like conditions.
Purpose of the Study:
- To investigate the morphological and physiological changes in the sensory retina of mice lacking SOD1 (Sod1(-/-)).
- To determine the impact of SOD1 deficiency on retinal function and cellular integrity over time.
Main Methods:
- Electroretinography (ERG) to assess retinal function.
- Retinal morphometric analysis to quantify cell nuclei.
- Electron microscopy to examine cellular ultrastructure.
- Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and activated caspase-3 detection to evaluate cell death pathways.
Main Results:
- ERG a- and b-wave amplitudes were reduced in senescent Sod1(-/-) mice, worsening with age.
- Retinal morphometry revealed fewer nuclei in the inner and outer nuclear layers.
- Electron microscopy showed cell swelling and mitochondrial degeneration, indicative of necrosis, not apoptosis.
- No significant increase in apoptotic cells or activated caspase-3 was observed in Sod1(-/-) retinas.
Conclusions:
- Sod1(-/-) mice exhibit progressive retinal degeneration, characterized by functional decline and necrotic cell death.
- These findings extend beyond previously reported age-related macular degeneration-like phenotypes.
- Sod1(-/-) mice serve as a valuable model for elucidating mechanisms of reactive oxygen species-induced retinal degeneration.
