When you want to fix something in your home, you can go to the Internet and find instructions, and often videos, that explain how to repair whatever is broken. Wouldn’t it be nice if it were that easy when it comes to eye disease or injury. While there aren’t any YouTube video that explain how to cure age-related macular degeneration, and if there are, it would be best to view them with a skeptical eye. No pun intended. Research is underway at the National Eye Institute (NEI) and at the University of Pittsburgh using AI and biologics that show it is possible to use these tools to develop therapeutics to treat eye diseases and injury.
Digital Twin
Scientists at NEI developed a digital facsimile or twin of the retinal pigment epithelial (RPE) cells. This provides a new tool for studying how eye cells organize themselves when they are healthy and when disease affects them. The twin was made from RPE cells from induced pluripotent stem (iPS) cells created by the Allen Institute for Cell Science, in Seattle. The 3D image data for the cells were collected from close to 4,000 view cells using an automated confocal microscope.
For RPE cell to function properly, they require top-to-bottom polarity. The top, or apical, side faces photoreceptors, where they recycle worn out parts. The bottom, or basal part, of the cell faces the blood supply, where it receives oxygen and nutrients and removes waste.
Using the data from the images, scientist trained an artificial intelligence (AI) algorithm called Polarity Organization with Learning-Based Analysis for RPE Image Segmentation, or POLARIS to recognize cell structures, shape and volume. Label were assigned to different images and segmentation data were generated at different stages of cell development.
The researchers paid special attention to polarity by quantifying the size and shape of the cell, its organelles, and cytoskeletal structures, including 3D spatial localization at various stages of development. They discovered is that healthy RPE cells follow a predictable path when they develop into a polarized state.
The AI-driven atlas of polarized and non-polarized RPE cells gives scientists a reference for studying how diseases, like age-related macular degeneration affect RPE at the cellular and subcellular level. This digital twin provides a new tool, for therapeutic development and for studying other diseases that affect cell polarity.
“By combining AI with mathematical modeling, we’ve created a window into cellular processes that were previously hidden from view,” said the study’s first and a senior author, Davide Ortolan, Ph.D., NEI research follow. “This technology doesn’t just help us understand what’s happening in AMD, it gives us a platform to discover how to fix it.”
Living Eye Drop
When you get a cut or skin your knee, you put on some ointment and a bandage and the injury heals faster. Now you can do something similar with your eyes. Scientists at the University of Pittsburgh School of Medicine (Pitt) researchers have developed an experimental living eye drop that uses a bacterium that is in the eye to support corneal wound healing. The study, published in Cell Reports, demonstrated in mouse models that the microbe Corynebacterium mastitidis (C. mastitidis) can be genetically modified to secrete an anti-inflammatory medicine that promotes healing after a corneal injury.
Since tears wash medications away, treating diseases of the ocular surface diseases often required multiple applications of eye drops. Researchers at Pitt studied an alternative delivery method, by engineering C. mastitidis to continuously secrete cytokine interleukin10 (IL10), a small protein that regulates inflammation. Mice with scratched corneas were treated with this engineered bacterium experienced faster healing than those treated with unmodified bacteria or saline. When the IL10 receptor was blocked, the benefit was gone, which confirms the effect depended on the protein.
Researchers also created a version that releases human IL10. This improved wound closures in in lab-grown human corneal cells and reduced inflammatory signaling in immune cells. These finding suggest that engineered bacterium could be adapted for use in people.
The great thing about this approach is its flexibility. Researchers could engineer the bacterium to deliver different genes, cytokines, growth factors or other proteins in order to treat specific eye diseases. Of course, this is in the early stages of development. Still, it provides a pathway to explore whether or not engineered live biotherapeutics could be used to deliver anti-inflammatory or regenerative molecules to the eye.
Both of these projects show how research is uncovering innovative ways to potentially treat eye disease. Whether it is through the use of a digital twin or an engineered bacterium, scientists are gaining new knowledge, expanding treatment options and bringing hope to patients with eye disease.
Sources:
https://www.medschool.pitt.edu/news/pitt-scientists-engineer-living-eye-drop-support-corneal-healing