From hagfish to membrane: Modeling age-related macular degeneration

Bruch’s membrane is a layer in the retina that helps to regulate the exchange of biomolecules, nutrients, oxygen, fluids and metabolic waste between the retina and the general circulation. Bruch’s membrane gets thicker with age, and breakdown of the membrane is implicated in age-related macular degeneration (AMD). However, studying the connection between an aging Bruch’s membrane and deterioration caused by AMD is challenging in live subjects due to the slow progression of the disease and the complexity of isolating specific layers of the retina. Creating an in vitro model, or a model developed in a laboratory setting, of Bruch’s membrane that mimics both its healthy and aged states would help researchers understand the relationship between physical changes via aging and AMD. The ideal model should be smooth, nonporous and capable of supporting cell growth. It should also replicate the changes that occur with age in thickness, stiffness and permeability (leakiness).

Previous models of Bruch’s membrane have captured some of its properties but not all. The most common model is a plastic membrane called a Transwell, which supports cell culture in the retina but is much thicker and stiffer than the natural membrane and cannot easily replicate changes from aging. Other models partially represent Bruch’s membrane but are difficult to produce and/or lack certain crucial aspects required to study AMD.

Professor Elizabeth Vargis and her team from Utah State University have now successfully demonstrated that hagfish slime proteins can accurately replicate human Bruch’s membrane. The researchers were able to properly grow retinal cells on hagfish slime proteins and proved that the membrane mimics stages of aging and disease. They published their research in ACS Biomaterials Science & Engineering. “By using these models, scientists can better understand the role of Bruch’s membrane in the development of age-related eye diseases,” Vargis said. “This research provides an affordable and widely available option.”

Sources:

ScienceDaily, September 13, 2023; see source article E Rickabaugh et al, ACS Biomaterials Science & Engineering, 2023; 9 (8): 5051 DOI: 10.1021/acsbiomaterials.3c00411