Protecting the Retina: Adjuncts to Glycemic Control‡
By Jeffery Anshel, O.D., FAAO and Kelly C. Heim, Ph.D.
Glucose homeostasis is a cornerstone of good health. When circulating glucose is not disposed and utilized properly, it can interact with cellular proteins, altering their structure and function. This process, known as glycation or glycosylation, is linked to the formation of reactive oxygen species and immune mediators known as cytokines. The blood vessels are particularly sensitive to all of these events– particularly the small and extremely delicate vasculature within the eye.1
The retina is the part of the eye that converts light into electrical impulses that make vision possible. For over 5 million American adults, blood glucose functionally affects the retina through biochemical interactions with the small blood vessels that supply it. According to the CDC, the number of individuals is expected to grow to approximately 16 million by 2050.
Fortuitously, the three major mechanisms underlying the effect of glucose on retinal vasculature (glycation, ROS and cytokine formation) complement the primary pharmacologic actions of several antioxidants, phytochemicals and essential fatty acids (Figure 1). Accordingly, animal and human research on these agents has shown efficacy in protecting the retina and supporting visual performance. While glycemic control and regular eye exams comprise the essential foundation of support, mounting evidence supports 6 specific nutritional strategies as effective adjuncts:‡
- Lutein and zeaxanthin. Individuals with high levels of lutein and zeaxanthin are more likely to sustain normal retinal function and related measurements such as visual acuity, contrast sensitivity, and macular fluid balance. In clinical studies, significant support has been evident after only 3 months of supplementation with lutein (6 mg/day) and zeaxanthin (0.5 mg/day) per day.2‡
- Alpha-lipoic acid (ALA). This powerful antioxidant quenches superoxide, a free radical that forms upon glucose exposure. More importantly, ALA directly moderates the protein glycation pathways in ocular tissues. Studies suggest that ALA also supports retinal capillary integrity through mitochondrial renewal, maintenance of endothelial cell populations, and moderation of vascular endothelial growth factor (VEGF), which regulates angiogenesis.3-5‡
- Curcumin. Curcumin is an antioxidant polyphenol that moderates the release of cytokines that circulate when plasma glucose is abundant.6,7 Like ALA, curcumin also targets VEGF.6 In a study of 77 patients, researchers evaluated Meriva®, a highly bioavailable phytosome preparation of curcumin. Subjects received 200 mg total curcuminoids per day while following a standard eye health management plan. Microcirculatory and clinical evaluations indicated significant support for vascular integrity, blood flow and visual acuity after only 4 weeks. No effects were observed in the group following the standard management plan alone.7‡
- Pycnogenol®. This polyphenol-rich extract of French maritime pine bark is well known for its protective effects on capillaries. To date, six clinical trials involving a total number of 1335 individuals, have evaluated its effects on the retina, and positive outcomes include retinal blood flow, vascular integrity, and visual performance.8 In a randomized controlled trial of 46 patients, Pycnogenol® provided significant support for healthy retinal thickness and fluid balance after 3 months. Blood flow in the central retinal artery changed from 34 to 44 cm/s in the Pycnogenol® group, with negligible effects in the control group. The most significant result was the change in visual acuity from 14/20 at baseline to 17/20 after only 2 months of supplementation. No significant changes were observed in the control group.9‡
- Resveratrol. Mechanistically similar to curcumin, resveratrol exerts multiple ocular health benefits.10 Preclinical studies indicate significant support for superoxide dismutase activity, moderation of cytokine expression, and maintenance of cell viability within the thin layers comprising the retina.11 Like curcumin, resveratrol is an antioxidant polyphenol with systemic metabolic benefits, maintaining healthy insulin and glucose responses to dietary fat and carbohydrate.‡
- Omega-3 essential fatty acids. EPA and DHA are essential for overall ocular health. DHA is a critical structural lipid and signaling molecule in retinal cell membranes, and preclinical studies show that DHA-rich diets maintain the structure, integrity and repair capacity of retinal capillaries.12-14 Proposed mechanisms of EPA include moderation of prostaglandin metabolism and VEGF activity.15‡
|Figure 1. How circulating glucose can affect the retina. Protein glycation,reactive oxygen species (ROS) formation and cytokine production are major underlying mechanisms. Dietary supplements target one or more processes.‡|
Seeing the big picture
While these modalities clearly support the retina, they concurrently address a critical underpinning—glucose homoeostasis. The systemic benefits of ALA, polyphenols and omega-3 fatty acids include support for insulin receptor function, glucose uptake by muscle, and vascular endothelial function. By virtue of coinciding ocular and systemic effects, these supplements, taken singly or in combination, can enhance the efficacy of any metabolic health protocol.‡
- Rask-Madsen C, King GL. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab (2013) 17(1):20-33.
- Hu BJ, Hu YN, Lin S, Ma WJ, Li XR. Application of lutein and zeaxanthin in nonproliferative diabetic retinopathy. Int J Ophthalmol (2011) 4(3):303-306.
- Kowluru RA, Odenbach S. Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes (2004) 53(12):3233-3238.
- Santos JM, Kowluru RA. Role of mitochondria biogenesis in the metabolic memory associated with the continued progression of diabetic retinopathy and its regulation by lipoic acid. Invest Ophthalmol Vis Sci (2011) 52(12):8791-8798.
- Nebbioso M, Pranno F, Pescosolido N. Lipoic acid in animal models and clinical use in diabetic retinopathy. Expert Opin Pharmacother (2013) 14(13):1829-1838.
- Aldebasi YH, Aly SM, Rahmani AH. Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways. Int J Physiol Pathophysiol Pharmacol (2013) 5(4):194-202.
- Steigerwalt R, Nebbioso M, Appendino G, et al. Meriva®, a lecithinized curcumin delivery system, in diabetic microangiopathy and retinopathy. Panminerva Med (2012) 54(1 Suppl 4):11-16.
- Schönlau F, Rohdewald P. Pycnogenol for diabetic retinopathy. A review. Int Ophthalmol (2001) 24(3):161-171.
- Steigerwalt R, Belcaro G, Cesarone MR, et al. Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther (2009) 25(6):537-540.
- Bola C, Bartlett H, Eperjesi F. Resveratrol and the eye: activity and molecular mechanisms. Graefes Arch Clin Exp Ophthalmol (2014) 252(5):699-713.
- Soufi FG, Mohammad-Nejad D, Ahmadieh H. Resveratrol improves diabetic retinopathy possibly through oxidative stress – nuclear factor κB – apoptosis pathway. Pharmacol Rep (2012) 64(6):1505-1514
- Yee P, Weymouth AE, Fletcher EL, Vingrys AJ. A role for omega-3 polyunsaturated fatty acid supplements in diabetic neuropathy. Invest Ophthalmol Vis Sci (2010) 51(3):1755-1764.
- Arnal E, Miranda M, Johnsen-Soriano S, et al. Beneficial effect of docosahexanoic acid and lutein on retinal structural, metabolic, and functional abnormalities in diabetic rats. Curr Eye Res (2009) 34(11):928-938.
- Tikhonenko M, Lydic TA, Opreanu M, et al. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function. PLoS One (2013) 8(1):e55177.
- SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res (2005) 24(1):87-138.