Macular Degeneration is the leading cause of blindness in the western world (JRSM, 2006), and is notoriously difficult to treat due to the limited understanding of the retina. To aid this, researchers have “engineered a new model of the retina” (Haseltine, 2023), that will provide an amazing resource to test gene and specific protein therapies.

One of the clear lessons that over 100 years of macular study has taught us is that the irreversible process of macular degeneration occurs when nutrients from the bloodstream can no longer reach the photoreceptor cells in the eye. This applies to both dry and wet AMD but occurs in different ways depending on the ailment.

The crucial protein that scientists have sought to test in a more controlled environment is VEGF (Vascular Endothelial Growth Factor) (Haseltine, 2023). The growth of blood vessels is closely tied to this protein, and the researchers Song et al. hoped to create a 3D model of the retina, which could “emulate both wet and dry age-related macular degeneration, while investigating molecular changes in the eye”.

The researchers used stem cells to build the four cell structures found within the retina, creating an ideal testing environment. Not only were the cells first engineered into a cell culture with correct layers, but the scientists went further by then translating this structure into a working and fully testable three-dimensional model.

In order to test the effectiveness of their model, the scientists would now have to induce a state of macular degeneration. First, they attempted to induce dry age-related macular degeneration, by injecting a lipid and protein serum. The proteins successfully accumulated, similarly, to dry-macular degeneration. A similar test was successfully performed to demonstrate the inducement of wet macular degeneration.

Most amazingly, the scientists were able to test whether the model would respond to macular-degeneration medications, after being induced with the conditions. This was the final assessment of the accuracy of the model, and a wet-macular degeneration medication called Bevacizumab successfully “treated” the induced wet macular degeneration.

By engineering a 3D, working model in this way, scientists have given themselves the ideal environment to test and analyse Macular Degenerative Diseases at high-frequency, while providing quicker results that can be seen in real time.

This has the potential to be a huge breakthrough, as touched on by Dr William A. Haseltine:

“This study is a significant step forward in our understanding of macular degeneration and in our ability to study diseases that affect the retina. As scientists continue to develop more accurate models of optical structures, we may eventually uncover treatments to prevent age-related blindness altogether.”

Sources:

Francis PJ. Genetics of inherited retinal disease. J R Soc Med. 2006 Apr;99(4):189-91. doi: 10.1177/014107680609900417. PMID: 16574971; PMCID: PMC1420779.

Song, M.J., Quinn, R., Nguyen, E. et al. Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration. Nat Methods 20, 149–161 (2023). https://doi.org/10.1038/s41592-022-01701-1