The Potential Role of the Cell’s Sugar Coat in Age-Related Macular Degeneration

All cells in the human body are covered in a complex sugar coat, the glycocalyx. This molecular coat is crucial for cell-to-cell communication and immune surveillance. An underlying mechanism of age-related macular degeneration (AMD) is the dysregulation of the innate immune system. The glycocalyx is involved in regulating these systems. Currently, we don’t know the precise composition of the sugar coats on cells in the eye at the site where AMD occurs. We will characterize the glycocalyx of diseased and healthy eyes to test whether differences contribute to immunological consequences.

Glycans, the complex carbohydrates that form the “sugar coat” on the outside of cells, provide one of the first points of contact for cell-to-cell communication and define molecular patterns in each cell. Firstly, we will characterize the glycans of the retina using mass spectrometry. We will also map and quantify the distribution of sialic acid linkage using immunohistochemical methods utilizing sialoglycan recognition probes. Lastly, we hypothesize that modifications of these glycans will alter the interaction with CFH, we will test this by manipulating the glycans on iPS-RPE cell.

Glycans coat the outside of every single cell in the human body, they are essential for cell-to-cell communication, and yet we know very little about them in the human retina. We believe changes in glycosylation could be leading to dysregulation of the complement system and playing a role in AMD pathology.

This study will provide a greater understanding of glycocalyx related complement factor H regulation of the alternative complement system in the context of the human retina. The contribution of the glycocalyx to disease continues to be an often overlooked aspect of molecular pathology. Understanding changes that contribute to the onset of the disease can provide avenues to prevent or slow the onset.