Mechanisms Underlying Early-Stage Changes in Visual Performance and Retina Function After Experimental Induction of Sustained Dyslipidemia

Visual and retinal function was measured in a mouse model of chemically induced, sustained dyslipidemia to determine the contribution of dyslipidemia to the pathogenesis of retinopathy in the context of metabolic syndrome. Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P...

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Published in:Neurochemical research 2018-08, Vol.43 (8), p.1500-1510
Main Authors: Montgomery, Christa L., Johnson, Heather M., Johnston, Thomas P., Koulen, Peter
Format: Article
Language:English
Subjects:
Acuity
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cholesterol
Cholesterol - blood
Correlation
Dyslipidemia
Dyslipidemias - blood
Dyslipidemias - chemically induced
Dyslipidemias - complications
Electroretinograms
Electroretinography
Electroretinography - drug effects
Electroretinography - methods
Frequency dependence
Male
Metabolic disorders
Metabolic syndrome
Mice
Mice, Inbred C57BL
Neurochemistry
Neurology
Neurosciences
Organic chemistry
Original Paper
Oxidative stress
Pathogenesis
Poloxamer - administration & dosage
Poloxamer - toxicity
Retina
Retina - physiology
Retinopathy
Triglycerides - blood
Vision Disorders - blood
Vision Disorders - chemically induced
Vision Disorders - etiology
Visual acuity
Visual perception
Visual stimuli
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description Visual and retinal function was measured in a mouse model of chemically induced, sustained dyslipidemia to determine the contribution of dyslipidemia to the pathogenesis of retinopathy in the context of metabolic syndrome. Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P-407), 14.5% w/w was delivered at a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (P-407 SQ) or intraperitoneally (P-407 IP) to P-407-treated mice, 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. Optomotor responses to stimuli of varying spatial frequency or contrast were used to measure visual acuity and contrast sensitivity. Retinal 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 
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Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P-407), 14.5% w/w was delivered at a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (P-407 SQ) or intraperitoneally (P-407 IP) to P-407-treated mice, 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. Optomotor responses to stimuli of varying spatial frequency or contrast were used to measure visual acuity and contrast sensitivity. Retinal 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. 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Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P-407), 14.5% w/w was delivered at a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (P-407 SQ) or intraperitoneally (P-407 IP) to P-407-treated mice, 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. Optomotor responses to stimuli of varying spatial frequency or contrast were used to measure visual acuity and contrast sensitivity. Retinal 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. 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Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P-407), 14.5% w/w was delivered at a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (P-407 SQ) or intraperitoneally (P-407 IP) to P-407-treated mice, 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. Optomotor responses to stimuli of varying spatial frequency or contrast were used to measure visual acuity and contrast sensitivity. Retinal 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.]]></abstract><cop>New York</cop><pub>Springer US</pub><pmid>29860619</pmid><doi>10.1007/s11064-018-2563-2</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0428-4288</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acuity
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cholesterol
Cholesterol - blood
Correlation
Dyslipidemia
Dyslipidemias - blood
Dyslipidemias - chemically induced
Dyslipidemias - complications
Electroretinograms
Electroretinography
Electroretinography - drug effects
Electroretinography - methods
Frequency dependence
Male
Metabolic disorders
Metabolic syndrome
Mice
Mice, Inbred C57BL
Neurochemistry
Neurology
Neurosciences
Organic chemistry
Original Paper
Oxidative stress
Pathogenesis
Poloxamer - administration & dosage
Poloxamer - toxicity
Retina
Retina - physiology
Retinopathy
Triglycerides - blood
Vision Disorders - blood
Vision Disorders - chemically induced
Vision Disorders - etiology
Visual acuity
Visual perception
Visual stimuli
title Mechanisms Underlying Early-Stage Changes in Visual Performance and Retina Function After Experimental Induction of Sustained Dyslipidemia
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