July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Mechanisms underlying early-stage changes in retina function after experimental induction of sustained dyslipidemia
Author Affiliations & Notes
  • Peter Koulen
    Ophthal/Vision Research Ctr, University of Missouri-Kansas City, Kansas City, Missouri, United States
    Biomedical Sciences, University of Missouri – Kansas City, School of Medicine, Kansas City, Missouri, United States
  • Christa Montgomery
    Ophthal/Vision Research Ctr, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • Heather Johnson
    Ophthal/Vision Research Ctr, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • Thomas Johnston
    Ophthal/Vision Research Ctr, University of Missouri-Kansas City, Kansas City, Missouri, United States
    Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • Footnotes
    Commercial Relationships   Peter Koulen, None; Christa Montgomery, None; Heather Johnson, None; Thomas Johnston, None
  • Footnotes
    Support  NIH grants AG027956, RR027093, EY022774 and EY027005; departmental challenge grant by Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3579. doi:
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      Peter Koulen, Christa Montgomery, Heather Johnson, Thomas Johnston; Mechanisms underlying early-stage changes in retina function after experimental induction of sustained dyslipidemia. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3579.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The study was designed to quantify retina function in a mouse model of chemically induced, sustained dyslipidemia, thereby dissecting the contribution of dyslipidemia to the pathogenesis of retinopathy in the context of one isolated component of metabolic syndrome.

Methods : Fifteen male C57BL/6Crl mice were divided into three groups. The triblock copolymer, Poloxamer 407 (P-407), was delivered to mice at 14.5% w/w and a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (“P-407 SQ” group) or intraperitoneally (“P-407 IP” group), whereas saline was administered at the same rate to control mice using only the subcutaneous route of administration. Total cholesterol (TC) and true triglyceride (TG) levels were quantified from plasma spectrophotometrically using enzyme-based colorimetric assays. Retina function was determined using Ganzfeld flash electroretinography (ERG).

Results : At 32 days, TC for the P-407 IP group was significantly elevated compared to saline controls (169.4±16.5 mg/dl, 0.001<P<0.01). TG levels for both the P-407 SQ (59.3±22.4 mg/dl, 0.01<P<0.05) and P-407 IP groups (67.7±18.0 mg/dl, 0.001<P<0.01) were significantly elevated relative to controls. Electroretinography demonstrated a very significant decline in the b/a ratio (1.80±0.11, P<0.01) for the P-407 IP group. The b/a ratio exhibited a moderate, significant correlation with TC levels (r = -0.4425, P=0.0392) and a strong, very significant correlation with TG levels (r = -0.6190, P=0.0021).

Conclusions : Delivery of P-407 via osmotic mini-pump resulted in the sustained, significant elevation of plasma TC and TG levels. This elevation in plasma lipid levels was correlated with a decline in inner retinal function similar to that observed in other forms of visual impairment originating from retina dysfunction. This mouse model of chemically induced, sustained dyslipidemia, therefore, can be used to delineate the specific contribution of dyslipidemia to pathological changes of the retina in the context of metabolic syndrome.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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