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    Home > Biochemistry News > Biotechnology News > Metabolomics helps to study the effect of omega-3 polyunsaturated fatty acids on inhibiting the development of myopia

    Metabolomics helps to study the effect of omega-3 polyunsaturated fatty acids on inhibiting the development of myopia

    • Last Update: 2022-08-30
    • Source: Internet
    • Author: User
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    Article title: Dietary ω-3 polyunsaturated fatty acids are protective for myopia
    Published Journal: PNAS
    Published Time: October 2021
    Impact Factor: 11.
    025
    Cooperative Client: Wenzhou Medical University Affiliated Eye and Optometry Hospital
    Baiqu Bio-Services: Free Fatty Acid Target Metabolism Omics Detection

    Research Background
    The proportion of myopia population in the world is increasing, and myopia is becoming an important public health problem in modern society
    .
    At present, the commonly used methods for controlling myopia include behavioral intervention, drug intervention and optical intervention, but these methods have their limitations
    .
    In search of a safe and accessible method for myopia control and prevention, this paper first evaluates the ability of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) as supplements to inhibit the development of myopia in different animal models, and then looks at DHA and EPA.
    Effects on choroidal blood flow (ChBP) and scleral hypoxia and effects on hypoxic cultured human scleral fibroblasts (HSFs), and finally to investigate the effect of omega-3 PUFAs supplementation on close-work-induced ChBP in human healthy subjects declining impact
    .


    Results
    01 Daily gavage of omega-3 PUFAs attenuates the development
    of myopia in guinea pigs and mice , Axial Length (AL) and Radius of Corneal Curvature (RCC) were measured to evaluate the effect of ω-3 PUFAs on the development of myopia in guinea pigs and mice
    .
    Form deprivation-induced myopia (FDM) guinea pigs were given omega-3 PUFAs for 2 weeks, and the diopter, VCD and AL were significantly smaller than those in the control group (Figure 1 AC); negative lens-induced myopia (LIM) guinea pigs were given omega-3 PUFAs orally Post-refraction and AL were also significantly decreased (Fig.
    1D-F); in FDM mice, the refraction after gavage with omega-3 PUFAs was 28.
    1% lower than that in the olive oil-gavage group (Fig.
    1G-I) 
    .
    These results indicate that daily gavage of omega-3 PUFAs can significantly inhibit the development of form deprivation myopia and negative lens-induced myopia in guinea pigs and mice
    .
     
    Figure 1.
    Effects of daily gavage of omega-3 PUFAs on diopter, VCD and AL in guinea pigs and mice
     
    02 Parabulbar injection of DHA alleviates the development of myopia
    in guinea pigs In FDM guinea pigs, placebo, 0.
    1% atropine and different concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were injected adjacent to the eyeball, and the diopter was measured.
    , ACD, LT, VCD, AL and RCC, to evaluate the effect of parabulbar injection on the development of myopia in guinea pigs
    .
    After 2 weeks of injection, the high-dose DHA group had a 35.
    3% lower degree of myopia progression compared with the control group, and at the same time had a significant inhibitory effect on VCD and AL, and the high-dose DHA group had a similar inhibitory effect as 0.
    1% atropine (Figure 2A-C).

    .
    The high-dose EPA group showed the same trend as 0.
    1% atropine in inhibiting the increase of FDM, VCD and AL, but there was no significant difference with the control group (Fig.
    2D-F)
    .
    These results indicate that DHA can significantly inhibit the development of FDM in guinea pigs
    .
     
    Figure 2.
    Effects of daily parabulbar injections of DHA and EPA on the development of myopia in FDM guinea pigs
     
    03 Changes of DHA and EPA contents before and after gavage of omega-3 PUFAs The DHA and EPA levels in
    the serum, sclera and retina of form-deprived guinea pigs were determined by gas chromatography-mass spectrometry to understand the changes of DHA and EPA
    .
    After 2 days of form deprivation, the content of DHA and EPA in serum and sclera decreased, and the content of DHA and EPA in retina increased; after 1 week of form deprivation, there was no significant difference in DHA and EPA in serum, sclera and retina (Figure 3)
    .
    After 3h administration of ω-3 PUFAs, serum DHA and EPA contents continued to increase; sclera DHA content increased significantly, but EPA content did not change significantly; retinal DHA and EPA content did not change significantly (Figure 4)
    .
    These results showed that DHA and EPA levels were abnormal in serum, sclera and retina during the development of myopia in guinea pigs
    .
     
    Figure 3.
    Changes of DHA and EPA levels in serum, sclera and retina of form deprived guinea pigs 
     
    Figure 4.
    Changed levels of DHA and EPA in serum, retina and sclera after gavage of omega-3 PUFAs in form-deprived guinea pigs.


    04 omega-3 PUFAs inhibited the decrease in choroidal blood flow in the development of myopia-scleral hypoxia cascade
    by optical coherence tomography ( OCT; Fig.
    5A) and OCT angiography (OCTA; Fig.
    5B) techniques to observe changes in choroidal thickness (ChT) and ChBP in guinea pigs after gavage and parabulbar injection
    .
    Both ChT and ChBP were significantly decreased in guinea pigs after form deprivation and negative lens induction; the decrease in ChT and ChBP was inhibited after gavage with ω-3 PUFAs (Fig.
    5C-F)
    .
    Parabulbar injection of DHA significantly inhibited the decline in ChT and ChBP (Fig.
    5G-J)
    .


    The decrease of ChBP caused scleral hypoxia and the up-regulation of HIF-1α protein expression.
    In order to detect the role of ω-3 PUFAs in this process, the scleral HIF-1α protein level was measured after gavage and parabulbar injection
    .
    The increase in scleral HIF-1α in form deprivation (FD-T) guinea pigs was inhibited after gavage of ω-3 PUFAs (Fig.
    5K, L)
    .
    Similar inhibition was observed after parabulbar injection of DHA and EPA (Fig.
    5M, N)
    .
     
    Figure 5.
    Effects of ω-3 PUFAs on ChT, ChBP and scleral HIF-1α protein levels in guinea pigs
     
    05ω-3 PUFAs can antagonize hypoxia-induced transdifferentiation of HSFs.
    HSFs
    affect scleral extracellular matrix (ECM) remodeling and the development of myopia.
    By studying the hypoxia response of HSFs in vitro, the potential of DHA and EPA on ECM remodeling was explored.
    influence
    .
    Under hypoxia, HIF-1α protein content increased, 1α type 1 collagen level decreased, and α-smooth muscle actin (α-SMA) content increased in HSFs (Figure 6)
    .
    DHA and EPA inhibited the hypoxia-induced decrease in collagen level and increase in α-SMA level (Fig.
    6A, CD)
    .
    These results suggest that DHA and EPA can inhibit myofibroblast transdifferentiation and restore collagen levels in HSFs under hypoxia
    .
     
     
    Figure 6.
    Effects of DHA and EPA on the hypoxic response of HSFs
     
    06ω-3 PUFAs can alleviate the decrease in human ChBP induced by continuous close work.

    The choroid of healthy human subjects after close work was measured, and it was found that before omega-3 PUFAs supplementation, excessive close work resulted in choroidal vascular index and vascular lumen.
    The area was significantly decreased and the phenomenon of choroidal vascular ischemia was increased; the decrease in choroidal vascular index was significantly attenuated after ω-3 PUFAs supplementation (Fig.
    7D-F)
    .
    These results suggest that close work leads to a decline in ChBP in humans, a decline that can be ameliorated by omega-3 PUFAs
    .

    Figure 7.
    Effects of omega-3 PUFAs on the human choroid after close work
     
    Conclusion
    Animal model experiments showed that ω-3 PUFAs inhibited the progression of myopia in guinea pigs and mice, and also inhibited the changes in choroidal structure, vascular system and sclera protein content
    .
    Changes induced by omega-3 PUFAs are critical for inhibiting scleral fibroblast transdifferentiation, maintaining normal scleral ECM remodeling, and inhibiting the development of myopia
    .
    In healthy human subjects, oral administration of omega-3 PUFAs attenuates the reduction in choroidal blood flow in the human eye caused by continuous near work and may have a protective effect on human vision
    .
    Both animal and human findings suggest that omega-3 PUFAs hold promise as an effective, safe, and convenient potential drug to control the progression of myopia
    .


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