Zinc and Ocular Health: From Antiquity to Modern Times

Wide-Ranging Cellular Functions of Zinc

Although zinc was found to be essential to living organisms in 1869, the idea that zinc deficiency can occur in humans wasn’t established until much later. Pioneering work by Annada Prasad, and co-workers in 1961-63, identified zinc deficiency as the cause of dwarfism and hypogonism prevalent in Iranian men at the time. It was later found that phytate, a compound naturally occurring in the high cereal grain-diets of these men, greatly impaired the absorption of zinc, leading to deficiency and retarded growth.

Since then, zinc has gained considerable recognition of its role in human health, and extensive research has elucidated its structural, regulatory and catalytic functions. Zinc plays an important role in stabilizing the structure of proteins and cell membranes; is involved in regulating gene expression and cell signaling; and over 100 different depend on zinc to help catalyze chemical reactions.

Zinc is required for proper growth and development, reproduction, and neurological function. Zinc also acts as an intracellular signal molecule for immune cells, and is involved in many immunological processes. Evidence suggests that even marginal deficiencies of zinc contribute to the decline in immune function associated with aging.

The Role of Zinc in Ocular Health and AMD

Zinc serves important functions in the eye as well. It is needed to mobilize vitamin A from the liver to the eye, and several key enzymes in the chorioretinal complex require zinc. In the retina and retinal pigment epithelium, zinc is believed to interact with taurine and vitamin A, modify photoreceptor plasma membranes, regulate the light-rhodopsin reaction, and modulate the passage of a neural impulse across synapses.

Zinc is thought to play a part in the development of age-related macular degeneration (AMD) for several reasons. First, zinc is highly concentrated in the retinal pigment epithelium, a key area of the retina that is affected by AMD. Secondly, the retinal content of zinc has been shown to decrease with age, as have the activities of some zinc-dependent retinal enzymes.

Ophthalmic Use of Zinc Dates to Ancient Times

While the benefits of supplemental zinc came to the forefront with publication of the AREDS trial in 2001, it appears that a role for this mineral in ocular health is rooted in history.

Italian researchers recently analyzed disc-shaped tablets that were uncovered in a 2000 year-old shipwreck off the coast of Tuscany, and reported their findings in the Proceedings of the National Academy of Sciences. The zinc-containing supplements were found in the Pozzino, a ship that sank in the 2nd century B.C., and were preserved underwater in oxygen-free metal tins called pyxis. According to the researchers, the composition and form of the tablets are consistent with an ophthalmic use of zinc as described in several ancient texts – some dating back as far as 300 B.C.

AREDS 2 and Future Research Directions

In 1988, David Newsome and colleagues reported that zinc-treated patients with drusen or AMD had significantly less vision loss than those receiving a placebo – findings that led to the AREDS trial. AREDS then demonstrated that treatment with zinc alone slowed the progression to advanced stages in patients with intermediate stage AMD, and when combined with antioxidants not only slowed disease progression but also reduced vision loss. The results of AREDS 2, expected later this year, may reveal whether a lower dose of zinc (25 mg) is as effective as that assessed in the first trial (80 mg).

There remains much to learn about zinc’s role in AMD. The exact mechanism(s) by which zinc slows this disease is still unclear, for instance. How does zinc interact with genetic risk factors for AMD such as different variants of complement Factor H? These questions and more await further investigation.

References

1. Giachi G, et al. Ingredients of a 2,000-y-old medicine revealed by chemical, mineralogical, and botanical investigations. PNAS ePub Jan 7, 2013.
2. Grahn BH, et al. Zinc and the Eye. J Am Coll Nutr 20:1-6-118, 2001.
3. Haase H and Rink L. Review: The immune system and the impact of zinc during aging. Immunity Ageing 6:9, 2009.
4. Nan R, et al. Zinc Binding to the Tyr402 and His402 Allotypes of Complement Factor H: Possible Implications for Age-Related Macular Degeneration. J Mol Biol; 408: 714–35, 2011.
5. Newsome DA, et al. Oral zinc in macular degeneration. Arch Ophthalmol 106:192-8, 1988.