We're excited to share the findings from our latest research, published in our recent paper, which sheds new light on the pathomechanisms behind Neuromyelitis optica spectrum disorder (NMOSD). This autoimmune condition, primarily affecting the brain, optic nerves and spinal cord, has puzzled researchers for years, particularly when it comes to understanding why certain tissues are more vulnerable to damage than others.
You can find a short description of our main findings below or you can dig deeper and check out the whole paper here: https://doi.org/10.1016/j.expneurol.2024.114919.
The Role of Oxidative Stress in NMOSD
Oxidative stress is known to play a significant role in various autoimmune diseases, including NMOSD. This stress can compromise the integrity of the endothelial barrier, the crucial boundary between blood vessels and tissues. When this barrier is impaired, it may allow autoantibodies to migrate into sensitive areas like the brain and retina, causing the characteristic damage seen in NMOSD.
Our study aimed to explore whether the susceptibility of endothelial cells (the cells lining the blood vessels) to oxidative stress might differ between the brain and the retina, potentially explaining the tissue-specific vulnerability observed in NMOSD patients.
A Comparative Study: Brain vs. Retinal Endothelial Cells
To delve into this, we compared primary human brain microvascular endothelial cells (HBMEC) with primary human retinal endothelial cells (HREC). These cells were exposed to varying concentrations of oxidative stress-inducing hydrogen peroxide (H2O2). By observing the effects on cell growth, barrier integrity, and complement protein secretion, we aimed to determine how each cell type responds to oxidative stress.
Key Findings: Differential Responses to Oxidative Stress
Our results were fascinating. When exposed to oxidative stress, both cell types showed a short-term adaptive response. Interestingly, at a low concentration of H2O2 (100 μM), the brain endothelial cells' barrier function actually improved beyond that of untreated cells. However, as the oxidative stress increased (500 μM H2O2), the brain cells' barrier was more disrupted compared to the retinal cells.
We also looked at the secretion of complement proteins, which are part of the immune system. Both cell types secreted complement factors H (FH) and I (FI). While FH secretion remained stable, FI secretion decreased under higher oxidative stress, indicating a complex interaction between oxidative stress and immune responses.
Implications for NMOSD and Beyond
These findings provide crucial insights into why certain tissues may be more susceptible to damage in NMOSD. The brain and retina's differential responses to oxidative stress might help explain the selective vulnerability observed in this disease. Understanding these mechanisms could open new avenues for therapeutic strategies, potentially leading to more effective treatments for NMOSD and other autoimmune diseases affecting the eye and brain.
We're hopeful that this research will contribute to a better understanding of NMOSD and inspire further studies to explore novel treatment options. Stay tuned for more updates as we continue to unravel the complexities of autoimmune diseases and the complement system.
Hannah
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