ARTICLE

The Relationship between Visual Performance and Macular Pigment in Non-diseased Eyes

BY K MEAGHER, JM NOLAN, S BEATTY

ision is one of the fundamental hand, refers to the ability of the visual the sensitivity of the brain to receive them. tools with which we interact system to discern the foreground from the Rod cells, of which there are with the world around us, and background, and is measured at a variety of approximately 90 million in the , good vision allows us to enjoy spatial frequencies (target sizes), and rests contain an called rhodopsin, which is so many aspects of life to the on the ability of the to discern activated under conditions of low levels of full. Ophthalmologists, by virtue of their objects of differing luminance within our incident light (as little as six photons), and pVrofession, are only too aware of the threat field of view. For example, we can easily these cells are therefore useful for low light to vision that ophthalmic pathology can distinguish a medium-sized object at low conditions or nightvision. Cones are represent. As a consequence, however, the contrast (i.e. a grey object in front of a white necessary for fine detailed vision, colour variability in visual performance and background), yet smaller-sized objects perception and visual resolution (acuity), experience in the normal eye has been require a greater degree of contrast with the and require greater amounts of incident light necessarily overlooked, as have measures to background if they are to be perceived. to be activated.The three types of cones, optimise vision in the absence of ocular Contrast sensitivity declines with known as S, M and L cones, contain pathology. increasing age [1,2] and poor contrast differing , which alter the spectral The variability in visual performance in the sensitivity is associated with reduced absorption properties of the photopigments. non-diseased eye is largely attributable to function related to vision, and this is reflected S-cone cells are activated bythe shorter differences in visual perception which are in difficulty with everyday tasks such as ‘blue’ wavelengths (approximately <470nm) subject to the respective and interactive reading, distinguishing traffic lights and road and are thus blue light sensitive, while M- influences of environment, anatomy and age. signage. Of note, CS, as a measure of visual cone cells are activated by medium The optical (blue light filtering), anatomic performance, is more reflective of a subject’s wavelengths (<530nm) and are green (central retinal) and biochemical (antioxidant) visual functioning than is VA, whether in a sensitive. The final type, L-cone cells, are properties of macular pigment (MP) are ideal diseased or in a healthy eye [3]. activated by the longer wavelengths of the to optimise vision in the normal eye and to visual spectrum (<560nm), thereby maintain effective physiological functionality The neurophysiological process of explaining their constituent photopigments’ of the visual system into old age. vision sensitivity to red. MP is composed of three carotenoids, The visual experience is created through a Beyond each cone’s primary colour lutein (L), zeaxanthin (Z) and meso - wide array of neurobiological processes. sensitivity, or spectrum absorption range, all zeaxanthin (MZ), to the exclusion of all other Photoreceptors in the inner layers of the three cone types are partially sensitive to the carotenoids in the diet and serum. MZ is the retina, known as rod and cone cells, contain other two spectral ranges. This allows dominant carotenoid in the epicentre of the photopigments within their cellular ganglion cells to compare the stimulation of macula, while Z and L are the dominant membranes, which convert the incident light the cones, which results in the visual carotenoids in the mid-periphery and (visible electromagnetic radiation) into perception of a wide spectrum of colours periphery of the macula, respectively. ‘electrical’ signals. Rod and cone (and not solely red, blue and green). photopigments are similar, in that they Measures of visual function consist of retinene bound (with both ends of degradation / Visual function, and the experience it results the molecule) to proteins, or opsins. death in for the subject, is a composite of a wide In order to produce a signal, the retinene The ultra-structural cellular composition of array of optical and neurophysiological must be activated by incident light, which photoreceptors, required for the necessarily processes, which are the result of an converts the retinene from 11-cis-retinal to sensitive nature of both rod and cone cells, exquisitely specialised and evolved visual 11-trans-retinal, detaching one end of the confers a susceptibility to oxidatively- system, and which can be reflected in a retinene molecule from the opsin, thus induced cell death. Reactive oxygen species plethora of psychophysical measures of initiating a nerve pulse or signal. The (ROS) are the inevitable by-products of visual performance, including object retinene then reverts to 11-cis-retinal and oxygen metabolism, and are therefore recognition, colour discrimination and depth re-binds to the opsin, to begin over anew. generated in large quantities in the human perception (to name but a few). These signals are compared and processed retina, a tissue which has the highest Visual acuity (VA), for example, is the by retinal ganglion cells and transmitted to oxygen metabolism in the mammalian world most commonly employed tool to assess the occipital cortex via the optic nerve, [4]. However, ROS production in tissue is spatial vision by eye care professionals, and where they are interpreted and converted increased further when irradiated with light, is a measure of the resolving power of the into a visual experience. Visual resolution especially short wavelength (high energy) eye at 100% contrast. (acuity) is a measure that is a direct light such as visible blue light. Indeed, the Contrast sensitivity (CS), on the other correlate of the strength of these signals and threshold for retinal injury is one thousand ARTICLE

times lower for blue light than for orange resulting in a bluish tinge or edge to an light (thereby limiting light-induced light under ambient conditions [4]. image, a phenomenon known as CA andone generation of ROS) and MP’s powerful ROS- Furthermore, the photoreceptor outer which adversely impacts CS. neutralising capacity, suggest that it is these segment membranes contain MP’s pre-receptoral filtration of blue light properties that limit age-related degradation polyunsaturated fatty acids (PUFAs) in very attenuates CA by reducing the amount of of photoreceptors, with a consequential and high concentrations, which, because of their defocused blue light incident upon the retina, parallel preservation of visual function into electron-dense molecular structures, are thereby optimising CS and enhancing visual old age [14]. susceptible to oxidation. As a result, a performance and experience [6,8]. Again, cytotoxic chain reaction ensues, thereby optimisation of visual function, in terms of Conclusion damaging the photoreceptors by depletion of CS under photopic and mesopic conditions, High levels of MP attenuate the adverse membrane PUFAs, in addition to is best achieved following supplementation impact of CA and light scatter on visual perpetuating the production of ROS. with a formulation containing all three of performance, because of the optical Reactive oxygen species, because of their MP’s constituent carotenoids (L, Z and MZ; properties of the pigment’s constituent inherent instability (free radicals, for Macushield™) [7]. carotenoids. Further, the biochemical example, contain one unpaired electron) and properties of L, Z and MZ are important for regardless of whether they are generated as Non-optical visual benefits of optimal physiological functionality of the a result of high oxygen metabolism or macular pigment neurobiological components of the visual irradiation with blue light, damage DNA, system, and appear to be important in the lipids, proteins and other important Neural efficiency maintenance of this system into old age. components essential for cellular functions. The functionality of the macular carotenoids is not limited to pre-receptoral light filtration Optical visual benefits of macular or anti-oxidant capacity, nor are these pigment compounds located exclusively in retinal Take home message tissue. Research has shown that L and Z – Augmentation of macular pigment Glare accumulate in the occipital and frontal (MP), and optimisation of its spatial Clinically, there are two types of glare, cortices, where they are the predominant profile, is best achieved following referred to as glare discomfort and glare xanthophylls [9], and where they are supplementation with a formulation that contains all three of MP’s disability. Discomfort glare is caused by thought to play an important role on gap constituent carotenoids (L, Z, and intense environmental light sources that junction communication [10] and in the MZ; Macushield ™). cause distraction and / or discomfort, such maintenance of neuronal membrane − L, Z and MZ are powerful as headlights of oncoming cars. integrity, thereby contributing to the antioxidants, and because they exert Glare disability is the result of light scatter, conditions required to optimise physiological this effect synergistically, the where the incident light is scattered by functionality of neural tissue, sometimes maximum collect antioxidant activity atmospheric particles (e.g. oxygen, nitrogen, referred to as neural efficiency [11]. Indeed, of MP requires the presence of all aerosols, etc) and / or by internal ocular the observed vision-enhancing effect of three of MP’s constituent structures (i.e. the lens and cornea). Short supplementation with a formulation carotenoids. wavelength (blue) light scatters to a greater containing all three macular carotenoids (L, − MP absorbs short wavelength (blue) extent than other wavelengths, and the Z and MZ; Macushield™) precedes visible light at a prereceptoral level, scattered light therefore superimposes a significant augmentation of MP, suggesting thereby attenuating chromatic bluish screen or ‘veil’ over the retinal image, that the observed benefits are not wholly aberration and minimising the adverse impact of scattered (mainly thereby increasing the increments of and solely attributable to the optical blue) visible light on the retinal luminance required to discern the foreground properties of MP, and that optimisation of image (known as veiling luminance). from the background. This phenomenon, neural efficiency may be playing a role [7]. − Optimum contrast sensitivity, under termed veiling luminance, therefore impairs mesopic and under photopic Age related decline in visual function CS and results in loss of visual resolution, conditions, is achieved following and is perceived by the subject as a loss of While retinal exposure to oxygen and light is supplementation with a formulation fine detail and distance perception. desirable, necessary and inevitable, the containing all three of MP’s As a consequence of MP’s pre-receptoral cumulative and adverse impact of lifelong constituent carotenoids (L, Z, and filtration of blue light, the adverse impact of exposure to their deleterious effects MZ; Macushield ™). veiling luminance on CS can be minimised, contributes to the observed age-related − Glare disability (reduced visual and CS therefore optimised [5,6]. decline in CS and retinal sensitivity, even in performance under glare conditions) Furthermore, it has recently been shown the absence of disease [12]. is ameliorated following that supplementation with a formulation One means of limiting such oxidative supplementation with a formulation containing all three of MP’s containing all three macular carotenoids (L, injury is through the effects of ROS- constituent carotenoids (L, Z, and Z, and MZ; Macushield TM ), in normal scavenging compounds, known as MZ; Macushield ™); subjects, results in enhanced CS (both antioxidants, which attenuate ROS-induced − MP limits oxidatively-induced mesopic and photopic) and alleviates the cell degradation [13]. Antioxidants are photoreceptor cell death, thereby impact of glare disability [7]. known to work synergistically, and include preserving retinal sensitivity (youthful enzymes (e.g. glutathione peroxidase) and a vision) into old age. Chromatic aberration variety of compounds that cannot be − The biochemical properties of L, Z Chromatic aberration (CA) is the result of the synthesised de novo by mammals (e.g. and MZ are important for optimal differential extent to which short, medium vitamins C and E, lutein, zeaxanthin and physiological functionality of the and long wavelengths are refracted by the meso-zeaxanthin, amongst others). neurobiological components of the eye. Short wavelength (blue) light is MP, composed of L, Z and MZ, visual system, and appear to be refracted to a greater extent than the other accumulates at the macula to the exclusion important in the maintenance of this visible wavelengths, and is therefore of all other carotenoids found in serum and system into old age. myopically defocused by 1.2 dioptres, diet. MP’s pre-receptoral filtration of blue References overleaf ARTICLE

References Katie Meagher 1. Elliott DB. Contrast sensitivity decline with ageing: a neural or optical Postgraduate Researcher, Macular Pigment Research Group, phenomenon? Ophthalmic Physiol Opt 1987; 7(4) :415-9. Department of Chemical and Life Sciences, 2. Tang Y, Zhou Y. Age-related decline of contrast sensitivity for Waterford Institute of Technology, second-order stimuli: earlier onset, but slower progression, than for first-order stimuli. J Vis 2009; 9(7) :18. Waterford, Ireland. 3. Charalampidou S, Loughman J, Nolan J, et al. Prognostic indicators and outcome measures for surgical removal of symptomatic nonadvanced cataract. Arch Ophthalmol 2011; 129(9) :1155-61. 4. Beatty S, Koh HH, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000; 45(2) :115-34. Dr John M Nolan 5. Stringham JM, Hammond BR. Macular pigment and visual Principal Investigator, Macular Pigment Research Group, performance under glare conditions. Optom Vis Sci Department of Chemical and Life Sciences, 2008; 85(2) ;82-8. Waterford Institute of Technology, 6. Hammond BR Jr, Wooten BR, Engles M, Wong JC. The influence of Waterford, Ireland. filtering by the macular carotenoids on contrast sensitivity measured under simulated blue haze conditions. Vision Res 2012; 63 :58-62. Dr Nolan is funded by the European Research Council (ERC), 7. Loughman J, Beatty S, Howard A, et al. Effect of carotenoid supplementation on macular pigment optical density and visual and the Howard Foundation. performance in normal observers: the Most Vision Trial. 2012. 8. Renzi LM, Hammond BR. The effect of macular pigment on heterochromatic luminance contrast. Exp Eye Res 2010: 91(6) :896-900. Professor Stephen Beatty 9. Craft NE, Haitema TB, Garnett KM, et al. Carotenoid, tocopherol, Consultant Ophthalmic Surgeon, and Director, and concentrations in elderly human brain. J Nutr Health Macular Pigment Research Group, Aging 2004; 8(3) :156-62. Department of Chemical and LifeSciences, 10. Stahl W, Sies H. Effects of carotenoids and retinoids on gap Waterford Institute of Technology, junctional communication. Biofactors 2001; 15(2-4) :95-8. Waterford, Ireland. 11. Zimmer JP, Hammond BR Jr. Possible influences of lutein and zeaxanthin on the developing retina. Clin Ophthalmol 2007; 1(1) :25-35. 12. Hepsen IF, Uz E, Sogut S, et al. Early contrast sensitivity loss and oxidative damage in healthy heavy smokers. Neurosci Res Comm Correspondence: Katie Meagher, Macular Pigment Research Group, 2003; 32(2) :123-33. Chemical and Life Sciences, Waterford Institute of Technology, Cork Road, Waterford. 13. Li B, Ahmed F, Bernstein PS. Studies on the singlet oxygen Email: [email protected] scavenging mechanism of human macular pigment. Arch Biochem Biophys 2010; 504(1) :56-60. Declaration of conflicting interest: Dr Nolan and Professor Beatty do consultancy work for 14. Snodderly DM, Hammond BR, Wooten BR. Preservation of visual nutraceutical companies, in a personal capacity, and as directors of Nutrasight Consultancy Limited. sensitivity of older subjects: association with macular pigment density. Invest Ophthalmol Vis Sci 1998; 39(2) :397-406.