New Study Uncovers Key Component in Age-Related Macular Degeneration, Paving the Way for Early Detection and Prevention
Age-related macular degeneration (AMD) is a common disease that affects aging individuals and is a leading cause of blindness in older adults. The good news is that blindness can be prevented if AMD is treated early. However, current treatment options are burdensome and expensive for patients and their families. Advanced AMD can only be treated in about 15% of cases by injecting medications directly into the eye.
Developing prevention or early detection tools could significantly improve the chances of avoiding advanced disease and help AMD patients maintain a better quality of life for longer. In pursuit of this goal, researchers from Vanderbilt University, along with investigators from the University of Alabama at Birmingham, the Delft University of Technology, University Hospital Bonn, and Molecular Horizon, collaborated to study the molecular pathways involved in the aging retina and the formation of deposits in the eye that confer a high risk for AMD.
Their groundbreaking research, published in the journal Frontiers in Ophthalmology, titled Lysolipids are prominent in subretinal drusenoid deposits, a high-risk phenotype in age-related macular degeneration, sheds light on a previously unknown component of AMD. The study delves into subretinal drusenoid deposits (SDD), also known as reticular pseudodrusen, which have recently been discovered to be strongly related to advanced AMD.
SDD, although indicative of an early stage of AMD, can affect the outcomes of treatments if not properly diagnosed. To gain a better understanding of SDD, the researchers used imaging mass spectrometry coupled with automated machine learning to analyze the molecular components. Additionally, they developed a nano-high-performance liquid chromatography tandem mass spectrometry method to analyze the lipids in small samples such as SDD in thin retina sections.
This study provides the most comprehensive data to date about the composition of SDD and identifies a salient component: lysolipids. Lysolipids are specialized molecules necessary for the synthesis and breakdown of cell membranes in retinal cells, particularly photoreceptors, which play a crucial role in vision initiation.
Furthermore, classic microscopy techniques revealed morphological details of the smallest and earliest lesions while identifying an enzyme important in the formation of lysolipids. The abundance of lysolipids in SDD suggests that lipid remodeling or degradation is involved in the formation of these deposits. This discovery not only offers important insights into SDD formation and function but also opens avenues to investigate additional molecular pathways critical to the development of AMD.
The successful collaboration among the research institutions was crucial for this study. The University of Alabama at Birmingham provided valuable histologic evaluation and access to freshly preserved human eye tissue, ensuring accurate microscopic and molecular analyses. Vanderbilt’s Mass Spectrometry Research Center (MSRC), equipped with cutting-edge technology, played a pivotal role in the sample processing and imaging mass spectrometry.
Delft University of Technology implemented automated machine learning strategies to analyze the vast amount of mass spectrometry data, while University Hospital Bonn and Molecular Horizons contributed additional tissue samples and data analysis tools, respectively.
Lead investigator Kevin Schey, a professor of biochemistry and deputy director of the MSRC, expressed his appreciation for the collaborative effort, stating that each team brought complementary skills and tools that made the study possible.
Moving forward, Schey and his team at Vanderbilt University will continue to delve into the mass spectrometry data and test hypotheses generated by this study. They also plan to improve their analytical chemistry methods to expand the available information about the early stages of AMD for the scientific community. Moreover, they hope that other researchers will investigate the biological mechanisms involved in deposit formation to find new ways to prevent or treat AMD.
In conclusion, this groundbreaking study uncovers an important component of age-related macular degeneration, providing valuable insights into the formation and function of subretinal drusenoid deposits. The researchers’ innovative approach and collaboration have paved the way for further investigations and potential advancements in early detection and prevention of AMD. This research brings hope to millions of older adults who wish to reduce the risk of vision loss and maintain their independence.
