There are valid reasons to study DMSO in relation to Eye Health
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Dimethyl sulfoxide (DMSO) is a chemical compound known for its ability to scavenge hydroxyl radicals and penetrate the blood-brain barrier. These properties suggest its potential as a protective agent against oxidative damage in retinal degenerations. A study conducted by Sellers et al. explored the effects of systemic DMSO treatment on light-induced retinal degeneration (LIRD) in mice.
Study Design and Methodology
The researchers utilized Balb/c mice, which were divided into groups receiving either a vehicle (Dulbecco’s PBS) or DMSO at a dosage of 3.74 g/kg administered intraperitoneally. Following an overnight dark adaptation, the mice received a second injection and were then exposed to either bright, toxic light (5,000 lux) or dim light (50 lux) for four hours. To assess retinal function, electroretinograms (ERGs) were recorded three weeks post-exposure. Retinal morphology was evaluated using optical coherence tomography (OCT) and microscopy of plastic-embedded eye sections. Additionally, protein oxidation was indirectly measured by assessing tyrosine nitration levels through a nitrotyrosine ELISA.
Key Findings
1. Electroretinogram (ERG) Results:
- In vehicle-treated mice exposed to bright light, there was a significant suppression of ERG a-wave and b-wave amplitudes by 89.3% and 88.9%, respectively, compared to dim light controls.
- Conversely, DMSO-treated mice exposed to bright light exhibited minimal suppression of a-wave (9.6%) and b-wave (7.1%) amplitudes.
- Notably, there was no significant difference between the ERG amplitudes of DMSO-treated mice exposed to bright light and those of vehicle-treated mice under dim light conditions.
2. Retinal Morphology:
- Bright light exposure in vehicle-treated mice led to the loss of most outer nuclear layer nuclei and the degeneration of inner and outer segments.
- In contrast, DMSO-treated mice exposed to bright light maintained retinal morphology comparable to that of dim light controls, indicating a protective effect of DMSO against structural damage.
3. **Protein Oxidation:**
- Bright light exposure in vehicle-treated mice resulted in a 211.9% increase in tyrosine nitration, suggesting elevated oxidative stress due to LIRD.
- Surprisingly, DMSO treatment led to an increase in nitrotyrosine levels by 289% in dim light conditions and 338.6% in bright light conditions, indicating that DMSO treatment was associated with increased tyrosine nitration regardless of light exposure intensity.
Technical Explanation
Electroretinography (ERG) is a diagnostic test that measures the electrical activity of the retina in response to light stimuli. The a-wave reflects the function of photoreceptor cells, while the b-wave is associated with the activity of bipolar and Müller cells. A significant reduction in these wave amplitudes indicates impaired retinal function. Optical coherence tomography (OCT) is a non-invasive imaging technique that provides high-resolution cross-sectional images of the retina, allowing for the assessment of retinal layer integrity. Tyrosine nitration is a post-translational modification of proteins that occurs under oxidative stress conditions, serving as a biomarker for nitrosative stress. The nitrotyrosine ELISA quantitatively measures the levels of nitrotyrosine-modified proteins, providing an indirect assessment of oxidative damage.
Conclusions and Implications
The study demonstrated that DMSO provides significant protection against functional and structural retinal damage induced by bright light exposure in mice. However, the unexpected increase in tyrosine nitration levels with DMSO treatment suggests that its protective mechanism may not be due to its antioxidant properties. The authors propose that DMSO might induce a form of preconditioning, potentially through the induction of mild oxidative stress, which in turn confers protection against subsequent, more severe oxidative damage.
These findings open avenues for further research into the mechanisms by which DMSO exerts its protective effects in retinal degenerations. Understanding these mechanisms could lead to the development of novel therapeutic strategies for conditions characterized by oxidative retinal damage.
Study Design and Methodology
The researchers utilized Balb/c mice, which were divided into groups receiving either a vehicle (Dulbecco’s PBS) or DMSO at a dosage of 3.74 g/kg administered intraperitoneally. Following an overnight dark adaptation, the mice received a second injection and were then exposed to either bright, toxic light (5,000 lux) or dim light (50 lux) for four hours. To assess retinal function, electroretinograms (ERGs) were recorded three weeks post-exposure. Retinal morphology was evaluated using optical coherence tomography (OCT) and microscopy of plastic-embedded eye sections. Additionally, protein oxidation was indirectly measured by assessing tyrosine nitration levels through a nitrotyrosine ELISA.
Key Findings
1. Electroretinogram (ERG) Results:
- In vehicle-treated mice exposed to bright light, there was a significant suppression of ERG a-wave and b-wave amplitudes by 89.3% and 88.9%, respectively, compared to dim light controls.
- Conversely, DMSO-treated mice exposed to bright light exhibited minimal suppression of a-wave (9.6%) and b-wave (7.1%) amplitudes.
- Notably, there was no significant difference between the ERG amplitudes of DMSO-treated mice exposed to bright light and those of vehicle-treated mice under dim light conditions.
2. Retinal Morphology:
- Bright light exposure in vehicle-treated mice led to the loss of most outer nuclear layer nuclei and the degeneration of inner and outer segments.
- In contrast, DMSO-treated mice exposed to bright light maintained retinal morphology comparable to that of dim light controls, indicating a protective effect of DMSO against structural damage.
3. **Protein Oxidation:**
- Bright light exposure in vehicle-treated mice resulted in a 211.9% increase in tyrosine nitration, suggesting elevated oxidative stress due to LIRD.
- Surprisingly, DMSO treatment led to an increase in nitrotyrosine levels by 289% in dim light conditions and 338.6% in bright light conditions, indicating that DMSO treatment was associated with increased tyrosine nitration regardless of light exposure intensity.
Technical Explanation
Electroretinography (ERG) is a diagnostic test that measures the electrical activity of the retina in response to light stimuli. The a-wave reflects the function of photoreceptor cells, while the b-wave is associated with the activity of bipolar and Müller cells. A significant reduction in these wave amplitudes indicates impaired retinal function. Optical coherence tomography (OCT) is a non-invasive imaging technique that provides high-resolution cross-sectional images of the retina, allowing for the assessment of retinal layer integrity. Tyrosine nitration is a post-translational modification of proteins that occurs under oxidative stress conditions, serving as a biomarker for nitrosative stress. The nitrotyrosine ELISA quantitatively measures the levels of nitrotyrosine-modified proteins, providing an indirect assessment of oxidative damage.
Conclusions and Implications
The study demonstrated that DMSO provides significant protection against functional and structural retinal damage induced by bright light exposure in mice. However, the unexpected increase in tyrosine nitration levels with DMSO treatment suggests that its protective mechanism may not be due to its antioxidant properties. The authors propose that DMSO might induce a form of preconditioning, potentially through the induction of mild oxidative stress, which in turn confers protection against subsequent, more severe oxidative damage.
These findings open avenues for further research into the mechanisms by which DMSO exerts its protective effects in retinal degenerations. Understanding these mechanisms could lead to the development of novel therapeutic strategies for conditions characterized by oxidative retinal damage.