The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

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The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Fundamental statistics in psychology and education.

Clinics in Developmental Medicine

Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins

OBJECTIVES: To assess the relationship between a broad range of vision functions and measures of physical performance in older adults. DESIGN: Cross-sectional study. SETTING: Population-based cohort of community-dwelling older adults, subset of an on-going longitudinal study. PARTICIPANTS: Seven hundred eighty-two adults aged 55 and older (65% of living eligible subjects) had subjective health measures and objective physical performance evaluated in 1989/91 and again in 1993/95 and a battery of vision functions tested in 1993/95. MEASUREMENTS: Comprehensive battery of vision tests (visual acuity, contrast sensitivity, effects of illumination level, contrast and glare on acuity, visual fields with and without attentional load, color vision, temporal sensitivity, and the impact of dimming light on walking ability) and physical function measures (self-reported mobility limitations and observed measures of walking, rising from a chair and tandem balance). RESULTS: The failure rate for all vision functions and physical performance measures increased exponentially with age. Standard high-contrast visual acuity and standard visual fields showed the lowest failure rates. Non-standard vision tests showed much higher failure rates. Poor performance on many individual vision functions was significantly associated with particular individual measures of physical performance. Using constructed combination vision variables, significant associations were found between spatial vision, field integrity, binocularity and/or adaptation, and each of the functional outcomes. CONCLUSIONS: Vision functions other than standard visual acuity may affect day-to-day functioning of older adults. Additional studies of these other aspects of vision and how they can be treated or rehabilitated are needed to determine whether these aspects play a role in strategies for reducing disability in older adults.

Is vision function related to physical functional ability in older adults

Objectives: To assess driving self-restriction (vision related and nonvision related) in relation to vision test performance of older adults.



Design: Cross-sectional study.



Setting: Population-based cohort of community-dwelling older adults.



Participants: Six hundred twenty-nine current drivers aged 55 and older had driving behavior, health, and physical function assessed and vision function tested in 1993–95.



Measurements: Self-report of driving restriction as vision or non-vision related and performance on a comprehensive battery of vision tests (visual acuity; contrast sensitivity; effects of illumination level, contrast, and glare on acuity; visual fields with and without attentional load; color vision; temporal sensitivity; and the effect of dim light on walking ability).



Results: Demographic, health, and functional characteristics differed significantly between restrictors and nonrestrictors but not between vision- and nonvision-related restrictors. Controlling for potential confounding, only vision-related driving self-restriction was significantly associated with reduced performance on nonstandard measures of acuity. Poor depth perception was significantly associated with restriction for both vision- and nonvision-related reasons. Poor performance on attentional visual field tests, analyzed individually and in combination with standard field tests, was not associated with driving self-restriction.



Conclusion: Older adults with early changes in spatial vision function and depth perception appear to recognize their limitations and restrict their driving even if they do not acknowledge the visual impairment as the cause for restriction. Poor visual attention, a risk factor for crashes, may not be recognized. Additional studies of driving self-restriction in relation to risk factors for crashes in older adults may help refine this strategy of reducing driving-related injury and death.

Vision and driving self-restriction in older adults.

The hypothesis was tested that the yellow macular pigment protects the human fovea from retinal neural damage caused by visible-light exposure over a lifetime. The sensitivities of the short-wavelength-sensitive-cone (S-cone) pathways and a long-wavelength-sensitive pathway were assessed across the central retina in a young group (average age, 23 years) and an older group (average age, 67 years) of normal healthy observers. No statistically significant difference was found at any retinal locations between the groups for the measures of long-wavelength sensitivity. However, the older group showed a significant differential loss of S-cone sensitivity across the retina compared with the younger group, with more loss of sensitivity at nonfoveal locations than at the fovea. This differential loss across the retina cannot be accounted for by yellowing of the crystalline lens, since lens effects are present equally at all retinal eccentricities. This result supports the hypothesis that the macular pigment protects the foveal area from light damage.

Short-wavelength-sensitive-cone sensitivity loss with aging: a protective role for macular pigment?

Visual evoked potentials were recorded in response to spatiochromatic stimuli modulated in different directions in cone-activation color space from subjects with congenital and acquired color defects. This technique was effective for detection and classification of both mild and severe forms of congenital deficits. Results suggest that the visual evoked potential is useful for early identification of color abnormalities in acquired deficits such as diabetes and that it is sensitive enough to detect regional retinal losses of sensitivity (e.g., as in central serous choroidopathy). The spatiochromatic visual evoked potential provides a systematic and sensitive indication of different color-vision anomalies.

Application of the spatiochromatic visual evoked potential to detection of congenital and acquired color-vision deficiencies

Purpose. To assess a broad range of vision functions in a large older population, to investigate the impact of vision function loss on visual performance measures, and to determine whether low contrast vision measures can predict future loss of visual acuity. Methods. A large battery of vision functions, including spatial vision measures, glare tests, visual fields, stereopsis, color vision, temporal sensitivity, reading performance, and face recognition, was administered to a population of 900 community-living older observers (mean age, 75.5 years; SD, 9.3 years; range, 58 to 102 years). A subsample (N = 596) was retested on average 4.4 years later (SD, 1.0 years). Results. Each vision function is affected differentially by aging. Some functions show little change with age (e.g., standard clinically measured high contrast visual acuity), whereas others demonstrate drastic losses with increasing age. For the oldest age group (>90 years), vision function losses ranged from 1.2 times worse than young observers (critical flicker/fusion frequency) to 18 times worse than young observers (low contrast acuity in glare). Visual performance measures, such as reading or face recognition, are also significantly affected by aging even in those with intact visual acuity. The results demonstrate that low contrast vision functions can successfully predict subsequent loss of high contrast visual acuity. Conclusion. Nonstandard vision function measures show significant losses with age that cannot be predicted by standard clinical measures. Measures of low contrast vision function allow clinicians to identify and monitor those patients at high risk for future vision loss.

Gunilla Haegerstrom-Portnoy

Papers

Is vision function related to physical functional ability in older adults

Vision and driving self-restriction in older adults.

Short-wavelength-sensitive-cone sensitivity loss with aging: a protective role for macular pigment?

Application of the spatiochromatic visual evoked potential to detection of congenital and acquired color-vision deficiencies

The Glenn A. Fry Award Lecture 2003: Vision in elders--summary of findings of the SKI study.