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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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).
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).
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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