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The Effect of Metformin Induced Activation on AMP-activated Protein Kinase on Retinal Light Damage

Himani Gubbi

Authors:  Himani Gubbi, Casey Keuthan, Lei Xu , John Ash

Faculty Mentor:  John Ash

College:  College of Medicine

Abstract

The retina is a complex tissue that houses photoreceptors crucial to the visual process. It is hypothesized that disruptions to the metabolism of the retina can cause photoreceptor degeneration. Previous literature has shown the importance of AMPK as an important regulator of cell metabolism in different cell types. We have previously shown that metformin, an activator of AMPK, can protect photoreceptors in models of retinal degeneration; however, the mechanism of this protection is unclear. This project further characterizes metformin in the protection of photoreceptors from light damage and investigates the neuroprotective role of two downstream metabolic regulators of AMPK, PGC1-α and PGC1-βthrough genetic knockout studies. For the metformin studies, BalbC mice were treated with metformin for one week before being exposed to damaging light for various time intervals after the last day of treatment. Optical coherence tomography (OCT) was performed to monitor retinal morphology after light damage. Retinal structure and function were also assessed in retinal-specific PGC-1 knockout mice in normal and light damage conditions. Together, this work provides more insight into the important metabolic processes of the retina and AMPK-mediated protection from retinal degeneration.

Poster Pitch

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Poster

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11 Responses
  1. Siri Ravuri

    This was a very informative poster presentation! I found the diagrams very helpful in how you stimulated the AMPK Pathways.

  2. Joseph Samman

    Interesting research Himani!

    I have no familiarity with biological sciences, so excuse my question if the answer is obvious…

    What kinds of applications might this research apply to? Do mice/rats have similar retinas to humans, or is this research primarily to gain understanding of some of the functions of the AMPK protiens?

    Thanks

  3. Himani Gubbi

    Hi Mr. Samman,

    Thank you! This research can have applications to human ophthalmology and potential treatments as the pathways that we are discussing, namely AMPK, can be translated into human metabolism as well. Mouse models are typically the first animals used to study potential retinal therapies because of their similar physiology to humans. Additionally, their well-studied genetics and protocols to genetically modify them, as we did for the PGC-1 mice, allow use to study the function of certain proteins in a controlled manner that can later be translated to humans. We hope that by studying drugs already used in humans, like metformin, we can understand human retinal function better and ways to protect it from degeneration. Please let me know if you have any more questions, thank you!

  4. Basil Hashimi

    Very insightful project! Previous knowledge serves me to understand that Metformin is a common medication known to be prescribed to those with Diabetes as it helps in maintaining blood sugar levels. I did not expect it to have an influence on retinal protection. I look forward to hearing more regarding your research in this field.