Researchers Discover the Missing Link in AMD Progression and Vision Loss

A study led by Dr. Nicolas Bazan, who holds the prestigious titles of Boyd Professor, the Ernest C. and Yvette C. Villere Chair for the Study of Retinal Degeneration, and serves as the Director of the Neuroscience Center of Excellence at the LSU Health New Orleans School of Medicine, proposes that age-related macular degeneration (AMD) has the effect of diminishing a vital fatty acid. This decline, in turn, hampers the formation of a group of protective molecules, ultimately diminishing the potential for repair.

Furthermore, this groundbreaking discovery may lead to new therapeutic possibilities for addressing AMD. The comprehensive findings of this research have been published in the journal Experimental Eye Research.

The study's findings indicate that age-related macular degeneration (AMD) leads to a reduction in docosahexaenoic acid (DHA) 22:6 in rod photoreceptor cells located in the peripheral retina. This reduction hinders the elongation of fatty acids required to produce very-long-chain polyunsaturated fatty acids (VLC-PUFAs). These VLC-PUFAs serve as the building blocks for elovanoids, which are bioactive chemical messengers derived from omega-3 very-long-chain polyunsaturated fatty acids.

Elovanoids, initially identified by the Bazan lab, have been demonstrated to restore damaged photoreceptor cells by repairing, remodeling, and regenerating healthy ones, thereby preserving the structural integrity. In cases of AMD, the diminished presence of these neuroprotective precursors for elovanoids in the peripheral retina results in uncompensated stress and cell loss.

"Biosynthetic fatty acid pathway insufficiencies may be a fundamental factor in the onset and progression of macular degenerative diseases leading to blindness," notes Dr. Bazan. "These findings open important immediate avenues for therapeutic exploration for AMD."

The research team also identified significant gender disparities in their findings. As per the National Institutes of Health, 66% of individuals affected by AMD are women. This higher prevalence of AMD in females is attributed to the influence of estrogen, which leads to elevated levels of DHA 22:6. However, as women age and experience a decline in estrogen levels, their DHA 22:6 levels also decrease, rendering them more susceptible to retinal degeneration.

"In AMD, the female retina loses peripheral rod VLC-PUFAs to about 33% less than in males, limiting elovanoid formation and its protective bioactivity," adds Bazan.

As reported by the Bright Focus Foundation, approximately 20 million people in the United States currently grapple with various forms of age-related macular degeneration. In 2019, an estimated 18 million individuals aged 40 and above were living with early-stage macular degeneration, while 1.49 million had progressed to late-stage macular degeneration. On a global scale, it is believed that around 200 million people are affected by AMD, a number projected to escalate to 288 million by the year 2040.

Age stands out as a significant risk factor for age-related macular degeneration. The likelihood of developing advanced age-related macular degeneration rises from 2% for those between the ages of 50 and 59 to nearly 30% for individuals over the age of 75. Moreover, the direct healthcare costs associated with visual impairment due to age-related macular degeneration in the United States, Canada, and Cuba are estimated at a staggering $98 billion.

Additional contributors to this study include Drs. William Gordon, Marie-Audrey Kautzmann, and Bok Kyoo Jun, in addition to Megan Cothern from LSU Health New Orleans' Neuroscience Center of Excellence and Dr. Zhide Fang from LSU Health New Orleans School of Public Health.

Reference

William C. Gordon et al, Rod-specific downregulation of omega-3 very-long-chain polyunsaturated fatty acid pathway in age-related macular degeneration, Experimental Eye Research (2023). DOI: 10.1016/j.exer.2023.109639