How Dietary Science is Revolutionizing Eye Health
Based on the ARVO 2021 Mildred Weisenfeld Award Lecture by Dr. Paul S. Bernstein
Imagine being a renowned eye specialist who can't stand the very vegetables that are considered crucial for eye health. This is the reality for Dr. Paul S. Bernstein, MD, PhD, of the University of Utah's Moran Eye Center, who delivered the prestigious 2021 Mildred Weisenfeld Award Lecture at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting. As a self-described "supertaster" who genetically rejects bitter dark green vegetables like broccoli and kale, Dr. Bernstein has turned this personal challenge into a professional mission to understand how nutrients benefit our eyes 1 .
His passion for ocular nutrition isn't about pushing unpleasant foods but about empowering patients with scientifically-backed dietary strategies that can prevent or delay blinding disorders. As Dr. Bernstein explains, "Nutrients that are naturally part of our daily diet can be an efficient and rational way to promote eye health and prevent or delay a variety of blinding disorders" 1 . This article explores the fascinating science behind how specific nutrients protect and enhance our vision, based on the groundbreaking research presented in Dr. Bernstein's award lecture.
Approximately 250 million people worldwide live with vision impairment, with up to 80% of cases being preventable or treatable through interventions including proper nutrition.
Through decades of research, Dr. Bernstein has identified a core principle: when the eye is specifically enriched with a nutrient, that nutrient likely has vital biological functions for vision. His work focuses on three key ocular-enriched nutrients that form the foundation of visual health 1 .
| Nutrient Category | Primary Functions in the Eye | Dietary Sources |
|---|---|---|
| Retinoids (Vitamin A) | Enables vision in dim light, supports retinal function | Liver, dairy products, orange fruits and vegetables |
| Carotenoids | Protects against blue light damage, enhances visual acuity | Kale, spinach, corn, orange peppers, eggs |
| Very-Long-Chain Polyunsaturated Fatty Acids (VLCPUFAs) | Maintain retinal structure, support cell membrane function | Fish, nuts, seeds, leafy greens |
Retinoids, commonly known as Vitamin A, represent the classic success story of ocular nutrition. The connection between certain foods and night vision has been recognized since antiquity, when people ate liver or specific fruits and vegetables to treat difficulty seeing in dim light.
The real breakthrough came in the 1930s and 1940s when Dr. George Wald identified a non-dietary metabolite of vitamin A called 11-cis-retinal as the retinoid responsible for capturing light in the vertebrate eye. This molecule forms the light-absorbing core of rhodopsin, the visual pigment in our rod cells that enables vision in low-light conditions 1 .
The second group of nutrients, carotenoids, includes lutein and zeaxanthin that accumulate in the macula—the central part of the retina responsible for sharp, detailed vision. These pigments act as natural blue light filters and antioxidants, protecting the delicate retinal tissues from phototoxic damage.
Dr. Bernstein's research has shown that higher levels of macular carotenoids are associated with reduced risk of age-related macular degeneration (AMD), the leading cause of vision loss in older adults 1 6 .
The third crucial group, very-long-chain polyunsaturated fatty acids (VLCPUFAs), are essential components of retinal cell membranes. They help maintain fluidity and flexibility of these membranes and play important roles in cellular signaling.
Diets rich in these healthy fats, particularly those from fish sources, have been linked to reduced risk of AMD and other retinal disorders 1 .
Dr. Bernstein's first major foray into ocular nutrition research began in 1981 when he entered Harvard Medical School as an MD-PhD student. He joined the laboratory of Dr. Robert R. Rando in the Department of Pharmacology, where he took on a project studying vitamin A metabolism in the vertebrate eye 1 .
Scientists already understood the basic outline of the visual cycle: when light strikes the 11-cis-retinal molecule in rhodopsin, it converts to all-trans-retinal, which then detaches from the protein. To regenerate visual pigment, this all-trans form must be converted back to 11-cis-retinal. There was just one problem: this conversion is thermodynamically unfavorable—meaning it requires energy. At thermal equilibrium, only 0.2% of any retinoid would naturally exist in the 11-cis form. Researchers hypothesized that a special enzyme must catalyze this reaction, but despite concerted efforts, no laboratory had detected this enzymatic activity 1 .
The isomerization of all-trans to 11-cis retinoids is thermodynamically unfavorable, requiring a specialized enzyme to drive the reaction forward despite natural equilibrium favoring the all-trans form.
Dr. Bernstein approached this problem methodically, first confirming that existing experimental approaches failed to detect isomerase activity. He then devised clever experiments using two known inhibitors of the visual cycle: diaminophenoxypentane (DAPP) and 4-methyl pyrazole (4-MP). These chemicals cause night blindness in humans by disrupting different parts of the visual cycle 1 .
Previous Understanding: Assumed to be all-trans-retinal
Dr. Bernstein's Contribution: Proved isomerization uses all-trans-retinol
Previous Understanding: Used 1-10% ethanol, destroying enzyme activity
Dr. Bernstein's Contribution: Reduced ethanol to 0.1%, preserved proteins
Previous Understanding: Unknown energy source for unfavorable reaction
Dr. Bernstein's Contribution: Identified retinyl ester hydrolysis as energy source
Previous Understanding: Unknown
Dr. Bernstein's Contribution: Later identified as RPE65, target of gene therapy
The implications of this discovery extended far beyond the laboratory. Nearly two decades later, other research groups identified the notoriously fastidious retinol isomerase as RPE65—which became the target for Luxturna, the first FDA-approved gene therapy for an inherited retinal disease 1 .
"There is a clear and logical progression of ocular nutrition research, starting with clinical observations and epidemiology to generate testable hypotheses. This is followed by laboratory-based biochemistry, physiology, and animal studies. Ultimately, it is desirable to do randomized, controlled human trials to provide reliable evidence and recommendations." - Dr. Paul S. Bernstein 1
Behind every vision research breakthrough lies an array of specialized research reagents that enable scientists to detect, quantify, and analyze biological molecules. These tools are indispensable for advancing our understanding of eye diseases and developing new treatments 3 5 .
| Reagent Type | Primary Function | Research Applications |
|---|---|---|
| Antibodies | Bind to specific proteins for detection and measurement | Identifying retinal disease biomarkers, tracking protein expression |
| siRNA | Silence specific genes to study their function | Studying gene function in retinal diseases, validating drug targets |
| Recombinant Proteins | Provide purified versions of naturally occurring proteins | Studying protein function, developing therapeutic interventions |
| Enzymes | Catalyze specific biochemical reactions | Supporting molecular biology techniques like PCR and DNA modification |
| Buffers and Dyes | Maintain stable pH and visualize biological structures | Creating optimal experimental conditions, staining cellular components |
The process of sourcing these reagents presents significant challenges for scientists. With hundreds of companies offering biological reagents and often incompatible data management systems, researchers can waste valuable time simply trying to identify and purchase necessary materials. Fortunately, new electronic resources are streamlining this process 5 .
Identifies appropriate reagents based on published studies
Compares prices across multiple vendors
Platform for scientific discussion and collaboration
Tools like Quartzy, LabFolder for efficient research management
Dr. Bernstein's four-decade journey in vision research demonstrates the transformative power of understanding how specific nutrients function in the human eye. From solving fundamental biochemical puzzles about how we see in dim light to developing practical nutritional strategies for preserving vision, his work embodies the translational potential of ocular nutrition research.
The principles he has established—that nutrients uniquely concentrated in the eye likely serve essential visual functions, and that dietary interventions can offer safe, affordable, and effective approaches to preventing blinding diseases—continue to guide the field forward. As research in this area advances, we move closer to a future where personalized nutritional strategies can help millions worldwide maintain their eyesight and quality of life 1 .
While the biochemistry is complex, the practical applications often involve foods readily available in our local markets or simple nutritional supplements, making eye health accessible to everyone.
What makes this science particularly compelling is its accessibility—while the biochemistry is complex, the practical applications often involve foods readily available in our local markets or simple nutritional supplements. The journey from laboratory discovery to real-world impact exemplifies how basic scientific research can ultimately empower individuals to take charge of their visual health through everyday choices.
As Dr. Bernstein's work continues to illustrate, sometimes the most profound medical advances come not from exotic new technologies, but from better understanding and harnessing the power of nutrients that have sustained human vision for millennia.