An in-depth look at cataract formation in dogs, and options for treatment.

Cataracts are common in older dogs. This article will look at the process behind their formation, along with integrative treatment options.

A close-up look at the lens

The “crystalline lens” is the living lens in host bodies. The adult crystalline lens is a unique structure; it lacks blood vessels and innervation yet is metabolically active. Because it is avascular, the lens must be bathed with aqueous humor to provide nutrients and remove waste products.

The lens can cause self-destruction of the eye, under the right circumstances. Proteins inside the lens are essentially “hidden” from the immune system, which means if lens proteins escape from the lens into the surrounding ocular fluid, the immune system can then detect them, misinterpret them as being foreign, and attack the eye. This is called lens-induced uveitis, common in canine eyes with any stage of cataract.

The lens is also unique in that it must change shape (accommodate) in order to optimally focus light. It is made up largely of special proteins called “crystallins”. In fact, the lens has the highest concentration of proteins in the body – over 40%. The oldest, or embryonic, lens tissue rests in the very center of the lens.

The lens is the only structure in the body that displaces cells inwards, rather than sloughing or shedding cells outwards. Early in life, the “nursery” or germinative lens epithelial cells, or LECs (which continuously migrate peripherally and mature to form overlapping layers of lens fiber cells), lie at the outermost aspect of the lens. The LECs live for the entire life of the host, or until cataract surgery removes the lens. New lens fiber cells are continually laid down as complex interlocking straps over the older ones. With time, the newer outer cells compress the older inner cells, resulting in increased density of the inner cells, which contributes to refraction of light.

Most proteins in the body only exist for a few hours to a couple of days. However, due to post-translational modifications, lens proteins become terminally modified and remain encased in the lens fiber cells. Therefore, they are immortal proteins as far as the host body is concerned; lens proteins must “live forever” and remain in an insoluble state in order to retain lens transparency and vision. In addition, the lens is exposed on a daily basis to profound oxidative stress caused by sunlight and also by endogenous and exogenous oxidative stressors, which challenge the antioxidant status of this most delicate and unique structure.

Cataracts or nuclear sclerosis

Clinically, a cataract is any opacity of the lens capsule or its cortex or nucleus, or any combination of these. In dogs, agerelated changes in the lenses begin to show after six years of age.^14-17 Nuclear sclerosis progresses gradually with time and, in most cases, vision is not clinically affected due to this change.

Many veterinarians mistakenly diagnose cataracts in aged dogs presenting with a history of reduced vision in dim light, when they actually have nuclear sclerosis and age-related (or senile) retinal degeneration, a slowly progressive loss of night vision common in aging dogs.^16,17 True nuclear sclerosis will not typically result in significant daytime vision loss, unless the dog is extremely old and therefore has extreme nuclear sclerosis.

Cataracts and antioxidants

Lens damage that causes cataracts is irreversible. Healthy lens fibers contain healthy transparent crystallin proteins. Unhealthy lens fibers contain crystallin proteins that are aggregating and becoming insoluble. Just as the clear protein in a raw egg turns white when cooked, as the proteins denature, clear lens proteins similarly turn white when the proteins inappropriately and permanently aggregate. Eggs cannot be unfried and cataracts cannot be reversed with conventional approaches. Holistic approaches can slow the progression and occasionally resolve small opacities.

In order to maintain its transparency and minimize the effects of oxidative stress, the lens has a variety of protective factors, including antioxidants and “chaperones”, to help keep the proteins soluble (and, therefore, the lens clear) as long as possible. Additionally, dogs with cataracts have been shown to possess lower glutathione and the antioxidant ascorbate than dogs without cataracts.^1-3

• A variety of nutritional antioxidants can complement the diet in order to enhance continuous regeneration of glutathione to its reduced state. These include vitamins C and E, selenium, bioflavonoids including carotenoids and polyphenols, coenzyme Q10, curcumin, and alpha lipoic acid.^4-7 Supplementation with these antioxidants would benefit canine breeds at risk for cataract formation, or in the early stages of cataract development. Even if cataracts progress in affected dogs, the antioxidants will make their eyes and bodies better candidates for cataract surgery.
• What else can be done to improve the chances of avoiding or slowing the onset of cataract formation? In humans, the quality of the diet affects the risk of age-related cataract formation. Aging lowers antioxidant levels throughout the body, including in the lens. By the age of 40 in humans, lens antioxidants are completely depleted; the analogous age in dogs is approximately five to six years, depending on the breed. Therefore, supplementing the diet with a variety of antioxidants known to be protective for the lens and against sunlight and other oxidative stressors may be helpful as well. While not yet researched in dogs, it is possible that a low fat grain-free diet that integrates colorful vegetables (which contain high levels of lutein and other carotenoids and flavonoids), along with excellent protein sources, may slow aging lens changes in dogs.
• Antioxidants such as vitamins C and E, lutein/ zeaxanthin and grapeseed extract have been shown to protect the lens against a variety of oxidative stressors. These antioxidants reduce reactive oxygen species, lessen lipid peroxidation, and therefore, decrease the risk of cataract development or progression.^8-10
• Lutein and zeaxanthin are oxycarotenoids or oxygenated carotenoids (i.e. xanthophylls) that selectively accumulate in the lens. Lutein may inhibit lipid peroxidation in both the lens and other ocular structures.¹¹ Research has shown that lutein and zeaxanthin supplementation in cultured lens epithelial cells protects lens lipids, proteins and DNA from oxidative damage, comparable to that of alpha-tocopherol (vitamin E).
• Grapeseed extract attenuates pathways associated with cataractogenesis including MAPK and PI3K. As has been shown in rodent models, there is potential for dietary modulation of these pathways to slow or inhibit cataract formation.^10,12,13

Progressive retinal atrophy

Progressive retinal atrophy (PRA) is an inherited disease affecting numerous breeds. Unlike genetic cataracts, many of the gene mutations causing PRA have been identified in a variety of breeds; DNA testing is available from Optigen® and the Animal Health Trust. Many dogs with PRA develop secondary toxic cataracts.

Supplementation with specific antioxidants that benefit retinal degeneration, including lutein/ zeaxanthin, Omega-3 fatty acids, vitamin E, zinc, coenzyme Q10, and green tea extract (EGCG), may slow or delay the progression of PRA. Even if cataracts do develop, the retinas would be optimally stabilized prior to cataract surgery, allowing for the return of optimal vision following surgery.

Causes of cataracts

The three leading causes of cataracts in dogs are:

1. Genetic predisposition
2. Cataracts secondary to diabetes mellitus
3. Toxic cataracts secondary to progressive retinal atrophy (PRA – see sidebar opposite).¹⁴

Other causes include:

– Excessive exposure to oxidative stressors (including ultraviolet radiation from sunlight, in addition to other forms of radiation)

– Normal aging changes

– Nutritional and metabolic imbalances

– toxins¹⁵

Trying to maintain healthy eyes (and especially healthy lenses) in spite of exposure to daily oxidative stress and aging involves multiple strategies. Therefore, when faced with cataracts of any cause, it may be next to impossible to avoid cataract progression and possible cataract surgery.

The diabetes connection

Diabetes mellitus is as prevalent in dogs as in humans; one in three dogs is estimated to become diabetic. As in humans, the obesity epidemic is the primary factor causing diabetes in dogs. Besides optimizing nutrition, losing weight, and getting proper daily exercise, daily insulin is needed in most patients to control hyperglycemia unless optimally treated with homeopathy or TCVM.  It is estimated that 68% to 75% of dogs with diabetes will develop cataracts within a year of diagnosis, despite the best of care.^18,19

Cataracts usually form very quickly, in both eyes simultaneously, causing lens-induced uveitis sometimes resulting in sterile endophthalmitis, glaucoma, absolute vision loss and removal of the eye(s), unless cataract surgery is performed as soon as possible. Once diabetes is diagnosed, support includes specific antioxidants, proper diet, homeopathy, TCVM and aldose reductase inhibitors. Inhibition of aldose reductase has been shown to prevent or delay diabetic cataract formation.²⁰

An ophthalmic drug is in development, in the form of an eyedrop called Kinostat™, which can significantly delay diabetic cataract progression in dogs by inhibiting aldose reductase.²¹ This eyedrop is not yet commercially available. However, aldose reductase activity can also be inhibited by using natural supplements including alpha lipoic acid, quercetin, rutin, and possibly turmeric.^22,23 Combining these with other antioxidants possessing strong anti-inflammatory, free radical-scavenging effects and lipid peroxidation inhibition, further help control oxidative stress. A recent study evaluating a commercially available antioxidant blend, OcuGLO^TM, showed that it significantly delayed cataract formation in diabetic dogs administered the supplement on a daily basis.²⁴

More about cataracts

What is important to understand is that once a cataract begins, many genes become activated or down-regulated in the LECs, and many are the same genes involved in neoplastic transformation. In addition, any stage of cataract can cause lens-induced uveitis, which further exacerbates cataract progression. The ultimate outcome is a progressing cataract. Many antioxidants including grapeseed extract, lutein, Omega-3 fatty acids, alpha lipoic acid, curcumin, and green tea extract (EGCG) possess anti-inflammatory properties and may be helpful in controlling this type of uveitis.^25,26

Thus far, there is no conventional medical means of clearing or curing an existing cataract that impairs vision. Anecdotally, homeopathic veterinarians have seen resolution of cataracts with careful prescription of the homeopathic medicines that match the constitution of the dog or cat.²⁷

N-Acetylcarnosine is a pro-drug of l-carnosine, which has been extensively studied in humans for age-related cataract.²⁸ A study evaluating the effect of N-acetylcarnosine in dogs with a variety of lens opacities, ranging from nuclear sclerosis to mature cataracts, showed no significant reduction of lens opacity in lenses with advanced cataracts.²⁹ Clinically, no board-certified veterinary ophthalmologist has witnessed success with these drops and sadly, many of the eyes “treated” with these drops progress to develop complications that do not allow surgery. Valuable time is lost in these dogs during which cataract surgery could have been performed, but instead, lens-induced uveitis relentlessly damages the eye.

Once a cataract is evident, referral to a veterinary ophthalmologist is recommended to most accurately diagnose ocular disease(s) and manage clinical and sub-clinical lens-induced uveitis. If the cataract progresses, only surgery to remove it will sufficiently address vision impairment. Careful monitoring for changes by veterinarians using homeopathy or TCVM, or frequent exams by a veterinary ophthalmologist, are recommended to avoid negative changes that can occur due to lens-induced uveitis.

References

¹Barros PS, Padovani CF, Silva VV, et al. “Antioxidant status of dog aqueous  humor after extracapsular lens extraction”. Braz J Med Biol Res 2003;36:1491-1494.

²Barros PSM, Angelotti AC, Nobre F, et al. “Antioxidant profile of cataractous English Cocker Spaniels”. Veterinary Ophthalmology 1999;2:83-86.

³Barros PS, Safatle AM, Queiroz L, et al. “Blood and aqueous humour antioxidants in cataractous poodles”. Can J Ophthalmol 2004;39:19-24.

⁴Milesi MA. “Oxidative stress, diseases and antioxidants”. Agro Food Industry Hi Tech 2006;17:6-9.

⁵Mandelker L. “Introduction to oxidative stress and mitochondrial dysfunction”. Vet Clin North Am Small Anim Pract 2008;38:1-30.

⁶Nordman T, Xia L, Bjorkhern-Bergman L, et al. “Regeneration of the antioxidant ubiquinol by lipoamide dehydrogenase, thioredoxin reductase and glutathione reductase”. Biofactors 2003;18:45-50.

⁷Raman T, Ramar M, Arumugam M, et al. “Cytoprotective mechanism of action of curcumin against cataract”. Pharmcol Rep 2016;68:561-569.

⁸Chandler HL, Colitz CMH. “Protection of canine lens epithelial cells from ultraviolet radiation induced apoptosis with grape seed extract”. 41st Annual Meeting of the American College of Veterinary Ophthalmologists 2010;422.

⁹Head KA. “Natural therapies for ocular disorders, part two: cataracts and glaucoma”. Altern Med Rev 2001;6:141-166.

¹⁰Barden CA, Chandler HL, Lu P, et al. “The effect of grape polyphenols on oxidative stress in canine lens epithelial cells”. Am J Vet Res 2008;69:94-100.

¹¹Xue C, Rosen R, Jordan A, et al. “Management of Ocular Diseases Using Lutein and Zeaxanthin: What Have We Learned from Experimental Animal Studies?” Journal of Ophthalmology 2015;2015:523027.

¹²Balu M, Sangeetha P, Murali G, et al. “Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats”. Brain Res Bulletin 2006;68:469-473.

¹³Williams DL. “Oxidation, antioxidants and cataract formation: a literature review”. Veterinary Ophthalmology 2006;9:292-298.

¹⁴Davidson MG, Nelms SR. “Diseases of the Canine Lens and Cataract Formation” In: Gelatt KN, Gilger BC,Kern TJ, eds. Veterinary Ophthalmology. 5 ed. Ames: John Wiley & Sons, Inc, 2013;1199-1233.

¹⁵Colitz CMH, Bomser JA, Kusewitt DF. “The Endogenous and Exogenous Mechanisms for Protection from Ultraviolet Irradiation in the Lens”. Int Ophthalmol Clinics 2005;45:141-155.

¹⁶Bellows J, Colitz CMH, Daristotle L, et al. “Common physical and functional changes associated with aging in dogs”. J Am Vet Med Assoc 2015;246:67-75.

¹⁷Bellows J, Colitz CMH, Daristotle L, et al. “Defining healthy aging in older dogs and differentiating healthy aging from disease”. J Am Vet Med Assoc 2015;246:77- 89.

¹⁸Beam S, Correa MT, Davidson MG. “A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases”. Vet Ophthalmol 1999;2:169-172.

¹⁹Wilkie DA, Gemensky-Metzler AJ, Colitz CMH, et al. “Spontaneous lens capsule rupture secondary to diabetes mellitus: Surgical outcome in canine eyes”. Vet Ophthalmol 2006;9:In press.

²⁰Kador PF, Akagi Y, Kinoshita JH. “The effect of aldose reductase and its inhibition on sugar cataract formation”. Metabolism 1986;35:15-19.

²¹Kador P, Webb TR, Bras D, et al. “Topical KINOSTAT™ ameliorates the clinical development and progression of cataracts in dogs with diabetes mellitus”. Veterinary Ophthalmology 2010;13:363-368.

²²Veeresham C, Rao AR, Asres K. “Aldose reductase inhibitors of plant origin”. Phytotherapy Research 2014;28:317-333.

²³Ou P, Nourooz-Zadeh J, Tritschler HJ, et al. “Activation of aldose reductase in rat lens and metal-ion chelation by aldose reductase inhibitors and lipoic acid”. Free Radic Res 1996;25:337-346.

²⁴Williams DL, Fitchie A, Colitz CMH. “An oral antioxidant formulation delaying and potentially reversing canine diabetic cataract: A placebo controlled masked pilot study”. International Journal of Diabetes and Clinical Research 2015;2:1-5.

²⁵Kidd PM. “Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts”. Altern Med Rev 2009;14:226-246.

²⁶Shoda H, Yanai R, Yoshimura T, et al. “Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in Association with Inhibition of Th1 and Th17 Cell Function”. PLoS One 2015;10:e0138241.

²⁷From cases by Drs. Betty Jo Black & Todd Cooney.

²⁸Babizhayev MA, Khoroshilova-Maslova IP, Kasus-Kacobi A. “Novel intraocular and systemic absorption drug delivery and efficacy of N-acetylcarnosine lubricant eye drops or carnicine biologics in pharmaceutical usage and therapeutic vision care”. Fundamental and Clinical Pharmacology 2012;26:644-678.

²⁹Williams DL, Monday P. The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study. Veterinary Ophthalmology 2006;9:311-316.