A Multi-Faceted Approach to Preventing Macular Degeneration

Researchers from the University of Wisconsin-Madison are developing an interesting, multi-faceted approach to thwarting macular degeneration. The process leads to massive compromises in vision and, often, blindness among millions of people.

In a recent study published in Proceedings of the Natural Academy of Sciences, the Wisconsin team focused on protecting the retinal pigment epithelium (RPE). The RPE is a subretinal layer of cells that provides many necessary functions, and also protects the photoreceptor cells. When it becomes compromised, macular degeneration begins. This often occurs with an activation of the complement system, itself supposed to be a protective mechanism that kills disease cells, that instead begins to attack the RPE.

In order to thwart the complement attack, the researchers employed a one-two punch treatment: a protein called CD59 that inhibits complement from boring holes in the RPE cells, and lysosomes, which plug those holes once they exist. In studies on mice, the authors claim to “provide evidence for two protective responses occurring within minutes of complement attack.”

"CD59 prevents the final step of attack that forms the pore," lead author Aparna Lakkaraju says in a press release. "Once a pore forms, the cell can move a lysosome to close it."

In a furthering of the study’s goals, it identifies acid sphingomyelinase (ASMase) as an enzyme related to the buildup of cholesterol in the RPE. ASMase is seen to inhibit their proposed reparative process, but can itself be inhibited by certain antidepressants. The colleagues administered desipramine to mice, and found that it restored CD59 levels.

The researchers hope their multi-faceted study will provide the basis for research into pharmaceuticals that can prevent macular degeneration.