ABSTRACT
Rare, nondietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are uniquely found in the retina and a few other vertebrate tissues. These special fatty acids play a clinically significant role in retinal degeneration and development, but their physiological and interventional research has been hampered because pure VLC-PUFAs are scarce. We hypothesize that if Stargardt-3 or age-related macular degeneration patients were to consume an adequate amount of VLC-PUFAs that could be directly used in the retina, it may be possible to bypass the steps of lipid elongation mediated by the retina's ELOVL4 enzyme and to delay or prevent degeneration. We report the synthesis of a VLC-PUFA (32:6 n-3) in sufficient quantity to study its bioavailability and functional benefits in the mouse retina. We acutely and chronically gavage fed wild-type mice and Elovl4 rod-cone conditional knockout mice this synthetic VLC-PUFA to understand its bioavailability and its role in visual function. VLC-PUFA-fed wild-type and Elovl4 conditional knockout mice show a significant increase in retinal VLC-PUFA levels in comparison to controls. The VLC-PUFA-fed mice also had improvement in the animals' visual acuity and electroretinography measurements. Further studies with synthetic VLC-PUFAs will continue to expand our understanding of the physiological roles of these unique retinal lipids, particularly with respect to their potential utility for the treatment and prevention of retinal degenerative diseases.
Subject(s)
Eye Proteins/genetics , Fatty Acids, Unsaturated/metabolism , Membrane Proteins/genetics , Retina/metabolism , Retinal Degeneration/metabolism , Animals , Biological Availability , Disease Models, Animal , Fatty Acids, Unsaturated/genetics , Fatty Acids, Unsaturated/pharmacology , Humans , Mice , Mice, Knockout , Retina/pathology , Retinal Degeneration/diet therapy , Retinal Degeneration/genetics , Retinal Degeneration/pathology , Visual Acuity/geneticsABSTRACT
Accumulation of bisretinoids such as A2E and its isomer iso-A2E is thought to mediate blue light-induced oxidative damage associated with age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). We hypothesize that increasing dietary intake of the macular carotenoids lutein and zeaxanthin in individuals at risk of AMD and STGD1 can inhibit the formation of bisretinoids A2E and iso-A2E, which can potentially ameliorate macular degenerative diseases. To study the beneficial effect of macular carotenoids in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (Abca4-/-)/ß,ß-carotene-9',10'-oxygenase 2 (Bco2-/-) double knockout (KO) mice that accumulate elevated levels of A2E and iso-A2E in the retinal pigment epithelium (RPE) and macular carotenoids in the retina. Abca4-/-/Bco2-/- and Abca4-/- mice were fed a lutein-supplemented chow, zeaxanthin-supplemented chow or placebo chow (~2.6 mg of carotenoid/mouse/day) for three months. Visual function and electroretinography (ERG) were measured after one month and three months of carotenoid supplementation. The lutein and zeaxanthin supplemented Abca4-/-/Bco2-/- mice had significantly lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow and improved visual performance. Carotenoid supplementation in Abca4-/- mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual function compared to the control diet group. There was a statistically significant inverse correlation between carotenoid levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Supplementation with retinal carotenoids, especially zeaxanthin, effectively inhibits bisretinoid formation in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Dioxygenases/genetics , Gene Expression Regulation , Lutein/pharmacokinetics , Macular Degeneration/drug therapy , Retinal Pigment Epithelium/drug effects , Zeaxanthins/pharmacokinetics , ATP-Binding Cassette Transporters/biosynthesis , Animals , Dioxygenases/biosynthesis , Disease Models, Animal , Electroretinography , Macular Degeneration/metabolism , Macular Degeneration/physiopathology , Mice, Inbred C57BL , Mice, Knockout , Retinal Pigment Epithelium/metabolism , Vision, Ocular/drug effectsABSTRACT
COVID-19 has altered many aspects of everyday life. For the scientific community, the pandemic has called upon investigators to continue work in novel ways, curtailing field and lab research. However, this unprecedented situation also offers an opportunity for researchers to optimize and further develop available field methods. Camera traps are one example of a tool used in science to answer questions about wildlife ecology, conservation, and management. Camera traps have long battery lives, lasting more than a year in certain cases, and photo storage capacity, with some models capable of wirelessly transmitting images from the field. This allows researchers to deploy cameras without having to check them for up to a year or more, making them an ideal field research tool during restrictions on in-person research activities such as COVID-19 lockdowns. As technological advances allow cameras to collect increasingly greater numbers of photos and videos, the analysis techniques for large amounts of data are evolving. Here, we describe the most common research questions suitable for camera trap studies and their importance for biodiversity conservation. As COVID-19 continues to affect how people interact with the natural environment, we discuss novel questions for which camera traps can provide insights on. We conclude by summarizing the results of a systematic review of camera trap studies, providing data on target taxa, geographic distribution, publication rate, and publication venues to help researchers planning to use camera traps in response to the current changes in human activity.
ABSTRACT
COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.
Subject(s)
Animal Migration , Animals, Wild , COVID-19 , Mammals , Quarantine , Animals , Humans , Animals, Wild/physiology , Animals, Wild/psychology , COVID-19/epidemiology , Mammals/physiology , Mammals/psychology , MovementABSTRACT
Purpose: Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel modality to investigate the human retina. This study aims to characterize the effects of age, pigmentation, and gender in FLIO. Methods: A total of 97 eyes from 97 healthy subjects (mean age 37 ± 18 years, range 9-85 years) were investigated in this study. This study included 47 (49%) females and 50 males. The pigmentation analysis was a substudy including 64 subjects aged 18 to 40 years (mean age 29 ± 6 years). These were categorized in groups A (darkly pigmented, 8), B (medium pigmented, 20), and C (lightly pigmented, 36). Subjects received Heidelberg Engineering FLIO and optical coherence tomography imaging. Retinal autofluorescence lifetimes were detected in two spectral channels (short spectral channel [SSC]: 498-560 nm; long spectral channel [LSC]: 560-720 nm), and amplitude-weighted mean fluorescence lifetimes (τm) were calculated. Additionally, autofluorescence lifetimes of melanin were measured in a cuvette. Results: Age significantly affected FLIO lifetimes, and age-related FLIO changes in the SSC start at approximately age 35 years, whereas the LSC shows a consistent prolongation with age from childhood. There were no gender- or pigmentation-specific significant differences of autofluorescence lifetimes. Conclusions: This study confirms age-effects in FLIO but shows that the two channels are affected differently. The LSC appears to show the lifelong accumulation of lipofuscin. Furthermore, it is important to know that neither gender nor pigmentation significantly affect FLIO lifetimes. Translational Relevance: This study helps to understand the FLIO technology better, which will aid in conducting future clinical studies.