Eyes may be a window into early Alzheimer’s detection

The eyes—specifically, the outer area of the retina—may provide a window into early detection of Alzheimer’s disease (AD) long before irreversible brain damage has occurred, according to new research from Houston Methodist. This discovery could dramatically change how the disease is diagnosed, monitored and treated.

“Retinal Müller glia alterations and their impact on ocular glymphatic clearance in an Alzheimer’s disease mouse model,” is online and will appear in an upcoming edition of the Journal of Alzheimer’s Disease. Led by Stephen Wong, Ph.D., the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering at Houston Methodist and director of T. T. & W. F. Chao Center for BRAIN, the study reveals how the peripheral retina (versus the central retina) could be a window into early diagnosis of AD.

“The eyes are indeed a window into the brain, but our study reveals that we have been looking at the wrong part of the window,” Wong said. “While most clinical eye exams focus on the central retina, the most critical early indicators of AD appear to be hidden at the periphery of the eye. By identifying these retinal changes that occur before the brain’s ‘plumbing’ system fails, doctors may eventually be able to use routine eye exams to catch and treat the disease years before memory loss begins.”

Cellular changes in the peripheral retina

The research was conducted in mouse models and revealed how Müller glia, or retinal support cells, respond in the earliest stages of the disease and undergo significant cellular and structural changes before other AD symptoms appear.

“Since the peripheral retina contains more glial cells than the central retina, we wanted to understand how these types of cells and blood vessels interact in different parts of the retina in early-stage AD,” said first author Glori Das, a graduate research assistant at the Wong Laboratory at Houston Methodist and an MD-Ph.D. student of Texas A&M School of Medicine.

Specifically, the researchers found that Aquaporin-4, a protein in the central nervous system that helps flush out metabolic waste, including AD-linked proteins, increases in the earliest stages of the disease. This shows up as stress in the peripheral retina, evidenced by the increased size and number of glial cells.

Implications for diagnosis and treatment

Wong said this is visual evidence that the body is working harder to maintain balance before the system eventually fails in later stages of the disease. He said this research could change how Alzheimer’s is diagnosed and monitored and could provide a new target for early-intervention drug development.

Wong also noted that a simple and noninvasive wide-field retinal imaging test versus expensive and invasive scans or other procedures could become a standard part of elder care during eye exams.

Additional study authors include Houston Methodist researchers Raksha Raghunathan, Lin Wang, Zhihao Wan, Matthew Vasquez and Hong Zhao. Zhao was the study’s co-corresponding author.