Diabetic retinopathy 2015 paper summary

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    (Carmel et al. 2015) “Role the receptor for advan

    glycation endproducts (RAin retinal vasodegeneratipathology during dia"etes

    mic

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    $ia"etic retinopathy and R

    • %rea&do'n of %R%

    • euronalglial dysfunction

    • Role of in*ammation

     innate immune cells• Retina innate immune cells  microglia and +

    • ,attern recognition receptors  RA!

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    !perimental procedure

    • Control ondia"etic 3 RA! /  Citrate "u

    • $ia"etic 6 3 RA! /  strepto7ocin

    • 8nduced at 12 'ee&s and hyperglycaemia con9days after in:ection in mice

    • lucometric analysis of tail pric& "lood sampl

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    !periment 1 RA! deletie4ects on retinal vasopermea

    • ;asopermea"ility assessed < 'ee&s after indudia"etes

    • Al"umin lea&age from retinal vasculature asse

    measure of %R% "rea&do'n

    • %R% ("lood retinal "arrier) assessed in cryose

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    Graph of albumin leakage from retinal blood vessels

    *p

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    !periment 2 Role of RA

    retinal vascular leucostas

    • =eucostasis assessed  *uorophorecon:ugateconcanavalinA

    •um"er of leucocytes counted

    • After < 'ee&s of dia"etes leucocytes adheren"lood vessels measured

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    Graph showing extent of retinal vascular leucostas*p

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    !periment > Assessment dia"etes related glial and neu

    dysfunction

    • Astrocytes and end feet of +uller cells  residimmune cells

    • lial responses measured using ?A, stainingdia"etic for 2< 'ee&s

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    Graph showing expression of GFAP in retinal Mul***p

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    !periment

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    Graph of total microglial cells***p

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    Graphs of activated (black bars) and resting (whmicroglia labelled with F4!" after #$ and $4

    *p

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    Conclusion

    • -tudy sho'ed dia"etic RA! / mice are protected frothe &ey early stage lesions of dia"etic retinopathy

    • ,rovided protection against vascular leucostasis andvasopermea"ility

    •,rotected from microglial activation after 12 'ee&s of d

    • Resident innate immune cells of retina  +uller glia andia"etic upregulation a"sent under RA! deletion

    • RA! involved in many vasodegenerative aspects of diaretinopathy suggesting a role for RA!