Antioxidants for Ocular Health

How these nutrients are proving beneficial for genetic eye disease.

by Dr. Car en Colitz, DVM, DACVO , P D an Dr. Terri M Calla, DVM, DACVO

Today’s dogs seem far more predisposed to cancer and other immune-mediated diseases than dogs in decades past. Conditions like these result from an excess of oxidative stress that cannot be counteracted by the endogenous antioxidant systems of the cells, or by the typical diet. The causes are likely numerous but certainly the quest for the perfect dog in a specific breed has led to many of the genetic diseases we see in veterinary medicine – and ophthalmology. The hybrid or designer breeds now popular are not immune even though the intent was to diminish the genetic issues; unfortunately, this did not entirely happen.

The most common genetic diseases we see in veterinary ophthalmology practice include cataracts, retinal degenerations and glaucoma. 1-3 Each breed or group of breeds likely have various mutation(s) that predispose that dog to one or more of these diseases. And unfortunately, you cannot change your genes. Thanks to the Dog Genome Project, the mutations for these diseases are already identified for some breeds, and many more will continue to be identified.

The new disciplines of nutrigenomics and nutrigenetics have helped cement nutrients as ways in which to modulate health. Nutrigenomics refers to genetic variation and its dietary response. 1 Nutrigenetics refers to the evolutionary aspects of diet and the role of nutrients in gene expression. 1 While the impact of diet and nutritional supplementation may not appear to affect inherited ophthalmic diseases in dogs, we might learn that genes that become involved in any of these diseases may be affected by what a dog eats. Likewise, this same concept of genetic variation and genenutrient interaction is important in drug metabolism and adverse reactions to drugs. 1 That said, an intake of certain nutrients may directly or indirectly modulate genes, including those that affect eye diseases.

Cataracts

While inherited cataracts in dogs are unlikely to be prevented or inhibited by nutriceutical supplementation, antioxidants will improve the environment of the lens cells and possibly reduce secondary sequellae to the ensuing oxidative stress caused by cataractogenesis. Some examples of nutrients shown to have aprotective effect on lens epithelial cells and/or cataract development include grapeseed extract, lutein/zeaxanthin, lycopene, zinc and coenzyme Q10.

Proanthocyanidins are powerful antioxidants found in grapeseeds, tea, nuts, pine bark and other plant extracts. They have a variety of effects, including free radical scavenging and anti-inflammatory, anti-viral and antimicrobial activities. They also potentiate the function of vitamins C and E. 5-7 A strain of rats (ICR/f) predisposed to hereditary cataracts due to lipid peroxidation were fed a diet containing grapeseed extract (GSE). Cataracts were slowed in progression and active glutathione (GSH) was higher in GSE-fed rats as compared to unsupplemented control rats. 2 Selenite-induced cataracts, a form of toxininduced cataract, were also significantly slowed or prevented by GSE. 3 In vitro studies on lens epithelial cells found that GSE reduced oxidative stress-induced reactive oxygen species production and attenuated stress-induced cell-signaling markers and NF-kB. 4, 5

Lutein and its coexistent isomer, zeaxanthin, are oxycarotenoids with two hydroxyl groups on either side of the molecule. They protect ocular tissues against photooxidative stress, quench and scavenge ultraviolet radiation-induced reactive oxygen species, inhibit lipid peroxidation, and filter blue light. 6 They are the only carotenoids found in the retina and lens (Bomser, unpublished results in dogs). 7 Lutein and zeaxanthin are potent antioxidants that inhibit lipid peroxidation. Though the literature strongly supports their role in protection against age-related cataracts in humans, there are no published reports investigating their inhibition of specific inherited or toxic cataracts in rodent models or other species. However, lutein and zeaxanthin may improve the lens environment during cataractogenesis through their antiinflammatory activity. 8 Cataractogenesis, regardless of the stage in dogs, causes inflammation 9, 10 and chronic uveitis can cause cataractogenesis. 11 Therefore, one can exacerbate the other.

Other plant extracts with protective effects against cataracts include lycopene and curcumin. Lycopene is a potent carotenoid found in tomatoes. Lycopene protects against selenite-induced cataracts as well as galactosemia-induced cataracts. 12, 13 Invitro, lens epithelial cells exposed to selenite improved antioxidant activity and glutathione levels when supplemented with lycopene, compared to unsupplemented control cells. Curcumin is the chief phenolic compound found in turmeric ( Curcuma longa). 14 Curcumin’s anti-inflammatory and antioxidant effects are due to its ability to induce antioxidant enzymes, decrease production of pro-inflammatory cytokines, sequester free radicals, inhibit neutrophil and macrophage function, and inhibit lipid peroxidation. 15-20 All cataractogenic processes have an imbalance in calcium, and curcumin may have anticataractogenic effects by preventing free radical-mediated accumulation of calcium in the lens. 21 Calcium (Ca 2+ ) is elevated in cortical, but not nuclear cataracts, 22 and excessive Ca 2+ can be detrimental to lens cells. Calcium is tightly regulated in the lens and its imbalance is associated with changes occurring during cataractogenesis. 23

Retinal diseases

Inherited degenerative or dystrophic retinal diseases have been a focus of research beginning in 1955. This research evaluated red Irish setters using the electroretinogram, 24 and was followed in 1965 by the description of a photoreceptor abiotrophy in the elkhound. 25 Since then, hundreds of publications have characterized and described the various forms of retinal dystrophy and degenerations in numerous breeds of dogs. With our improved understanding of gene cloning and the establishment of the Dog Genome Project, mutational analysis has identified specific mutations for these diseases in many breeds. As a result of this research, DNA testing is now available for 67 breeds so far.

Lutein and zeaxanthin selectively accumulate in the retina and lens. 3-5 Recovery of electroretinographic function in dogs with Progressive Retinal Atrophy (PRA) has been demonstrated following nutritional supplementation; these findings suggest the progression of canine PRA is inhibited by antioxidant supplementation, including lutein and zeaxanthin. 26 Regardless of the mutation causing retinal dystrophy or degeneration, there is cell death and oxidative stress. Since rods are the major source of oxygen utilization in the retina, their death results in deleterious oxygen levels and photoreceptor damage. 27, 28 Once the rods die, the cones gradually follow. It is hypothesized that cone death is due to oxidative damage possibly secondary to increased oxygen levels in the outer retina. 27, 28

A combination of antioxidants including alpha-tocopherol, ascorbic acid and alpha lipoic acid, reduced oxidative stress. Individually, alpha-tocopherol and alpha lipoic acid, both lipid soluble antioxidants, showed significant increases in cone numbers compared with the other groups. 27 Therefore, as long as enough cones survive in retinas with degenerative or dystrophic diseases, vision may be maintained or prolonged by the use of antioxidants.

Glaucoma

Oxidative stress is an important part of glaucoma. One theory is that an unstable ocular blood flow leads to repeated mild reperfusion events. 31 Elevations in intraocular pressure (IOP) damage retinal ganglion cells with secondary excitotoxicity and free radical generation. 32 Coenzyme Q10 has been shown to delay apoptosis in retinal ganglion cells resulting from high IOP. 33 Much of the information, thus far, pertains to humans with open angle glaucoma, and rodent models; therefore, confirmation of oxidative stress events and evaluation of the effects of antioxidants in canine glaucoma are warranted. Other antioxidants, including polyphenols (grapeseed extract) and EGCG (green tea extract), may help slow the progression of the damage occurring in glaucoma. 31

In summary, all diseases – including inherited ophthalmological conditions – have oxidative stress in their pathogenesis. The body’s numerous endogenous antioxidant systems fight the daily free radical damage that occurs with normal body functions, including digestion and metabolism and growth in young animals. However, an excess of oxidative stress, occurring with chronic lifelong situations such as inherited ophthalmic disease, depletes the endogenous antioxidant systems, and any antioxidants available from the diet. This likely exacerbates the progression of these diseases. Therefore, the use of antioxidant supplements as a complement to traditional therapy is likely beneficial.

Dr. Carmen Colitz is a board certified veterinary ophthalmologist with a PhD in Comparative and Experimental Medicine. She has extensive research experience involving antioxidants and how they affect eye health, particularly the lens. In addition, Dr Colitz discovered telomerase activity in cataracts and has over ten years research experience working in this field. Dr. Terri McCalla is a board certified veterinary ophthalmologist and owner of Animal Eye Care in Bellingham, Washington. Her research interest is in retinal pathology, and she has been in private specialty practice for over 20 years.

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