Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 05, 2024 1 month, 1 week, 4 days, 16 hours ago
Ophthalmology Updates: Introduction to a Breakthrough
A groundbreaking study has recently revealed the potential of Peptain-1 in preventing retinal capillary degeneration, a leading cause of vision loss. This
Ophthalmology Updates news report delves into the study conducted by researchers from the University of Colorado, Aurora-USA, focusing on how Peptain-1 can protect against retinal damage.
Peptain-1 shows promise in preventing vision loss
Understanding Retinal Capillary Degeneration
Retinal capillary degeneration occurs when the blood vessels in the retina are damaged, leading to significant visual impairment. This damage is often due to ischemia/reperfusion (I/R) injury, which can occur in various conditions, including diabetic retinopathy. Diabetic retinopathy is a common complication of diabetes, affecting millions worldwide and leading to blindness if not properly managed.
Ischemia refers to the lack of blood flow and oxygen to the tissue, and reperfusion is the subsequent restoration of blood flow. While reperfusion is necessary, it can also cause additional damage due to the sudden influx of oxygen and inflammatory mediators. This dual-phase injury is particularly damaging to the delicate structures in the retina.
What is Peptain-1?
Peptain-1 is a 20-amino acid peptide derived from the core domain of αB-crystallin, a protein known for its protective effects on cells. Previous studies have shown Peptain-1's ability to protect retinal ganglion cells in glaucoma models. This new research extends these findings, demonstrating that Peptain-1 can also prevent the apoptosis (programmed cell death) of human retinal endothelial cells (HRECs) and protect retinal capillaries in mice subjected to I/R injury. αB-crystallin belongs to a family of small heat shock proteins that play a crucial role in maintaining cellular integrity under stress conditions. It acts as a molecular chaperone, helping to prevent protein aggregation and supporting cell survival pathways. Peptain-1 mimics these beneficial properties, making it a promising candidate for therapeutic interventions in retinal diseases.
The Study's Methods and Findings
The researchers conducted a series of experiments to test the effectiveness of Peptain-1. They treated HRECs with Peptain-1 and exposed them to a mixture of proinflammatory cytokines, which are known to induce cell death. The results showed that Peptain-1 significantly reduced apoptosis in these cells.
In the animal model, 12-week-old C57BL/6J mice were subjected to I/R injury by elevating intraocular pressure and then restoring it. Peptain-1 was injected into the eyes immediately after the injury and again after seven days. Fourteen days post-injury, the researchers observed that Peptain-1-treated mice had significantly less retinal capillary degeneration compared to those treated with a scrambled peptide or vehicle control.
Detailed Study Insights
ong>-Protecting Endothelial Cells: The study demonstrated that Peptain-1 effectively entered HRECs and blocked the apoptotic pathway activated by proinflammatory cytokines. This was evidenced by a reduction in cleaved caspase-3 levels, a marker of apoptosis, and fewer TUNEL-positive cells, which indicate DNA fragmentation due to cell death.
The researchers used western blotting techniques to measure the levels of cleaved caspase-3 in cell lysates. They found a significant increase in cleaved caspase-3 in cells treated with the cytokine mixture compared to untreated cells. However, cells treated with Peptain-1 showed a marked reduction in cleaved caspase-3 levels, highlighting its protective effect against cytokine-induced apoptosis.
-Distribution in the Retina: When injected intravitreally, Peptain-1 was found throughout the retinal vessels within hours, suggesting efficient penetration and distribution. This rapid dispersion is crucial for its protective effects in acute injury settings.
To visualize the distribution of Peptain-1, the researchers used a fluorescently labeled version of the peptide. Confocal microscopy images showed that Peptain-1 was present in the retinal blood vessels and surrounding tissues just four hours after injection. This quick and widespread distribution is essential for timely intervention in conditions like I/R injury.
-Inhibiting Retinal Degeneration: The retinal capillaries of Peptain-1-treated mice showed significantly fewer signs of degeneration post-I/R injury. The protective effect of Peptain-1 was attributed to its anti-apoptotic properties and its ability to reduce inflammation and oxidative stress in retinal cells.
The researchers assessed retinal capillary degeneration by counting the number of acellular capillaries, which are indicative of capillary dropout and vascular damage. Mice treated with Peptain-1 had a significantly lower number of acellular capillaries compared to those treated with scrambled peptides or vehicle controls. This finding underscores the potential of Peptain-1 in preserving retinal vascular integrity.
-Reducing Neuroinflammation: Another key finding was that Peptain-1 reduced microglial activation and proinflammatory cytokine levels in the retina following I/R injury. Microglial cells, when activated, can exacerbate retinal damage through the release of inflammatory mediators. By reducing this activation, Peptain-1 helps to preserve retinal structure and function.
Microglia are the resident immune cells of the central nervous system, including the retina. Upon injury, they become activated and can adopt a proinflammatory phenotype that contributes to further tissue damage. The study showed that Peptain-1 treatment reduced the number of activated microglia, as well as the levels of proinflammatory cytokines such as IL-1β and TNF-α, suggesting an anti-inflammatory role for Peptain-1.
Implications for Diabetic Retinopathy
Diabetic retinopathy is a major cause of vision loss in adults, characterized by progressive damage to the retinal blood vessels. Chronic hyperglycemia in diabetes leads to increased oxidative stress and inflammation, which in turn cause endothelial cell dysfunction and death. This study's findings suggest that Peptain-1 could be a valuable therapeutic agent for preventing the early stages of diabetic retinopathy by protecting retinal endothelial cells and reducing inflammation.
Diabetic retinopathy progresses through several stages, starting with mild non-proliferative abnormalities and potentially advancing to proliferative diabetic retinopathy, where new, fragile blood vessels form and pose a risk of hemorrhage. By intervening early in the disease process, treatments like Peptain-1 could help maintain retinal health and prevent the severe complications that lead to vision loss.
Conclusion
This study suggests that Peptain-1 holds significant potential as a therapeutic agent for preventing retinal capillary degeneration and neuroinflammation. The researchers believe that with further development, Peptain-1 could be used to treat early stages of diabetic retinopathy and other conditions characterized by retinal ischemia.
The findings of this study were published in the peer-reviewed journal: Frontiers in Cellular Neuroscience.
https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2024.1441924/full
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https://www.thailandmedical.news/news/american-doctors-warn-that-covid-19-can-cause-vision-loss
https://www.thailandmedical.news/news/breaking-mild-covid-causes-a-slow-progressing-eye-debilitating-condition-that-most-are-not-even-aware-of-till-it-s-too-late
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