Understanding eye diseases is tricky enough. Knowing what causes them at the molecular level is even more confounding. Now, University of Iowa researchers have created the most detailed map to date of a region of the human eye long associated with blinding diseases, such as age-related macular degeneration. The high-resolution molecular map catalogs thousands of proteins in the choroid, which supplies blood and oxygen to the outer retina, itself critical in vision. By seeing differences in the abundance of proteins in different areas of the choroid, the researchers can begin to figure out which proteins may be the critical actors in vision loss and eye disease.
This molecular map now gives researchers clues why certain areas of the choroid are more sensitive to certain diseases, as well as where to target therapies and why. Before this, the medical community just didn’t know what was where.
What vision specialists know is many eye diseases, including age-related macular degeneration (AMD), are caused by inflammation that damages the choroid and the accompanying cellular network known as the retinal pigment epithelium (RPE). Yet they’ve been vexed by the anatomy. Why does it seem that some areas of the choroid-RPE are more susceptible to disease than others, and what is happening at the molecular level? The researchers set about to answer that question with nondiseased eye tissue donated by three deceased older individuals through the Iowa Lions Eye Bank. From there the team created a map that catalogs more than 4,000 unique proteins in each of the three areas of the choroid-RPE; the fovea, macula, and the periphery.
Why that’s important is now the researchers can see which proteins are more abundant in certain areas, and why. One such example is a protein known as CFH, which helps prevent a molecular cascade that can lead to AMD, much like a levee can keep flooding waters at bay. The UI researchers learned, though the map, that CFH is most abundant in the fovea. That helps, because now they know to monitor CFH abundance there; fewer numbers of the protein could mean increased risk for AMD, for instance.
Previous studies have compared the abundance of single proteins in the fovea, macula, and periphery. The UI choroid-RPE map corroborates findings from these studies, while also opening a whole, new avenue of research into thousands of proteins that may be involved in vision loss. The group likens it to a leap from the first topological drawings of a landscape to the detailed satellite images now seen.
The team were able to identify thousands of proteins simultaneously and develop a map that shows what are the patterns of proteins that make these regions unique. This has helped explain why certain genes are associated with macular degeneration, and helps point the medical community to new treatment targets.
Source: The University of Iowa
