Nutritional manipulation of primate retinas. IV. Effects of n−3 fatty acids, lutein, and zeaxanthin on S-cones and rods in the foveal region

Leung, Ivan; Sandstrom, Marita M.; Zucker, Charles L.; Neuringer, Martha; Snodderly, D. Max

doi:10.1016/j.exer.2005.03.009

Cited by 32 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27,28 Our own pilot work showed that fixation had no effects on measurement of xanthophylls. 28 Following perfusion, the retinas were dissected into three retinal areas: a 4 mm diameter circular punch centered on the fovea, the surrounding 4-8 mm annulus, and a portion of peripheral retina. Brain tissue was dissected from the dorsolateral frontal cortex/frontal pole, the occipital cortex, the cerebellum and the pons.…”

Section: Methodsmentioning

confidence: 92%

“…The same monkeys were used in a series of studies that examined the effect of xanthophyll-free diets and L and Z supplementation on macular pigment optical density, retinal xanthophyll levels measured by HPLC and the morphology of the retinal pigment epithelium and photoreceptors, as well as retinal sensitivity to blue light damage. 3,5,26-28 The details of the duration and method of supplementation were described in Johnson et al 3 …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

Vishwanathan

Neuringer

Snodderly

et al. 2013

Nutritional Neuroscience

Self Cite

132

120

View full text Add to dashboard Cite

Objectives Xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain tissue. The objective of the study was to evaluate the relationship between retinal and brain levels of these xanthophylls in non-human primates. Methods Study animals included rhesus monkeys reared on diets devoid of xanthophylls that were subsequently fed pure lutein or pure zeaxanthin (both at 3.9 μmol/kg*d, n=6/group) and normal rhesus monkeys fed a stock diet (0.26 μmol/kg*d lutein and 0.24 μmol/kg*d zeaxanthin, n=5). Retina (4 mm macular punch, 4-8 mm annulus and periphery) and brain tissue (cerebellum, frontal cortex, occipital cortex and pons) from the same animals were analyzed by reverse phase HPLC. Results Lutein in the macula and annulus were significantly related to lutein levels in the cerebellum, occipital cortex and pons, both in bivariate analysis and after adjusting for age, sex and n–3 fatty acid status. In the frontal cortex the relationship was marginally significant. Macular zeaxanthin was significantly related to zeaxanthin in the cerebellum and frontal cortex, while the relationship was marginally significant in the occipital cortex and pons in a bivariate model. Discussion An integrated measure of total macular pigment optical density, which can be measured noninvasively, has the potential to be used as a biomarker to assess brain lutein and zeaxanthin status.

show abstract

Section: Methodsmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

Vishwanathan

Neuringer

Snodderly

et al. 2013

Nutritional Neuroscience

Self Cite

132

120

View full text Add to dashboard Cite

show abstract

“…The macular pigment mainly consists of the retinal carotenoids lutein and zeaxanthin (Wustemeyer et al, 2003;Neuringer et al, 2004;Johnson et al, 2005;Leung et al, 2005;Barker et al, 2011;Lima et al, 2016). Its absorption spectrum lays between 400 and 540 nm with a peak at 460 nm.…”

Section: Fluorescence Lifetimes Of Retinal Fluorophores Ex Vivomentioning

confidence: 99%

Fluorescence lifetime imaging ophthalmoscopy

Dysli

Wolf

Zinkernagel

2017

Acta Ophthalmologica

View full text Add to dashboard Cite

a b s t r a c tImaging techniques based on retinal autofluorescence have found broad applications in ophthalmology because they are extremely sensitive and noninvasive. Conventional fundus autofluorescence imaging measures fluorescence intensity of endogenous retinal fluorophores. It mainly derives its signal from lipofuscin at the level of the retinal pigment epithelium. Fundus autofluorescence, however, can not only be characterized by the spatial distribution of the fluorescence intensity or emission spectrum, but also by a characteristic fluorescence lifetime function. The fluorescence lifetime is the average amount of time a fluorophore remains in the excited state following excitation. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is an emerging imaging modality for in vivo measurement of lifetimes of endogenous retinal fluorophores. Recent reports in this field have contributed to our understanding of the pathophysiology of various macular and retinal diseases.Within this review, the basic concept of fluorescence lifetime imaging is provided. It includes technical background information and correlation with in vitro measurements of individual retinal metabolites. In a second part, clinical applications of fluorescence lifetime imaging and fluorescence lifetime features of selected retinal diseases such as Stargardt disease, age-related macular degeneration, choroideremia, central serous chorioretinopathy, macular holes, diabetic retinopathy, and retinal artery occlusion are discussed. Potential areas of use for fluorescence lifetime imaging ophthalmoscopy will be outlined at the end of this review.

show abstract

“…Vertical sections from the central calotte that crossed near the foveal depression, and from the temporal and nasal calottes, were used for morphometry using methods and strategy as in previous work (e.g., La Vail et al, 2000;Hare et al, 2004;Leung et al, 2005). Contiguous fields, extending from the central retina into the far superior and inferior retina, were imaged at ϫ10 magnification with a camera (Olympus BH2; Olympus America, Melville, NY) attached to a microscope (Leica DFC480; Leica Microsystems, Bannockburn, IL).…”

Section: Necropsy and Histopathologymentioning

confidence: 99%

Safety in Nonhuman Primates of Ocular AAV2-RPE65, a Candidate Treatment for Blindness in Leber Congenital Amaurosis

et al. 2006

View full text Add to dashboard Cite

Leber congenital amaurosis (LCA) is a molecularly heterogeneous disease group that leads to blindness. LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV-RPE65 vector. Human ocular gene transfer trials are being considered. Our safety studies of subretinal AAV-2/2. RPE65 in RPE65 -mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses. We now test the hypothesis that there can be vectorrelated toxicity to the normal monkey, with its human-like retina. Good Laboratory Practice safety studies following single intraocular injections of AAV-2/2. RPE65 in normal cynomolgus monkeys were performed for 1-week and 3-month durations. Systemic toxicity was not identified. Ocular-specific studies included clinical examinations, electroretinography, and retinal histopathology. Signs of ocular inflammation postinjection had almost disappeared by 1 week. At 3 months, electroretinography in vector-injected eyes was no different than in vehicle-injected control eyes or compared with presurgical recordings. Healed sites of retinal perforation from subretinal injections were noted clinically and by histopathology. Foveal architecture in subretinally injected eyes, vector or vehicle, could be abnormal. Morphometry of central retina showed no photoreceptor layer thickness abnormalities occurring in a dose-dependent manner. Vector sequences were present in the injected retina, vitreous, and optic nerve at 1 week but not consistently in the brain. At 3 months, there were no vector sequences in optic nerve and brain. The results allow for consideration of an upper range for no observed adverse effect level in future human trials of subretinal AAV-2/2. RPE65. The potential value of foveal treatment for LCA and other retinal degenerations warrants further research into how to achieve gene transfer without retinal injury from surgical detachment of the retina. KeywordsLeber congenital amaurosis, blindness, mutated dogs, retina, injection, dogs and safety data with rAAV-2/2.RPE65. Questions about systemic and retinal toxicity are asked in a nonhuman primate, the only mammal with a foveate retina like that of humans, to determine whether there is sufficient safety to initiate human clinical trials.

show abstract

Nutritional manipulation of primate retinas. IV. Effects of n−3 fatty acids, lutein, and zeaxanthin on S-cones and rods in the foveal region

Cited by 32 publications

References 36 publications

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

Fluorescence lifetime imaging ophthalmoscopy

Safety in Nonhuman Primates of Ocular AAV2-RPE65, a Candidate Treatment for Blindness in Leber Congenital Amaurosis

Contact Info

Product

Resources

About