Abstract
Purpose :
The study was designed to quantify retina function in a genetic mouse model of diabetes, in which sustained dyslipidemia was induced chemically. The goal of the study was to identify if dyslipidemia in the presence of hyperglycemia resulted in either a synergistic, or merely additive, exacerbation of retinopathy in the context of the two most clinically-relevant components or features of the metabolic syndrome.
Methods :
Two cohorts of mice, C57BL/6 and C57BL/KsJ-db/db mice were divided into two groups each. One group of each strain received the triblock copolymer, poloxamer 407 (P-407), administered by intraperitoneal injection (“P-407” and “P-407 db/db” groups) with saline as a control in the remaining two groups (“saline” and “db/db” groups). Blood glucose, total cholesterol (TC) and total triglyceride (TG) levels were quantified using enzyme-based colorimetric assays. Retina function was measured using electroretinography (ERG) and visual acuity was determined behaviorally.
Results :
TC and TG levels were normal in both saline controls and db/db mice, but were significantly elevated in the P-407 group (P<0.05), while levels of the same lipids were further elevated in the P-407 db/db group when compared to the P-407 group levels (P<0.0001). ERG measurements of scotopic retina function showed a significant decline in the b/a wave ratio of the P-407 and db/db groups and a further reduction for the P-407 db/db group when compared to controls (P<0.01). Similarly, behavioral assessment of the optomotor reflex indicated reduced visual acuity for both the P-407 and db/db groups and was further reduced in the P-407 db/db group when compared to either the P-407 or the db/db groups (P<0.001).
Conclusions :
Dyslipidemia in the presence of hyperglycemia synergistically exacerbated disease severity of diabetic retinopathy. P-407 administration significantly elevated plasma TC and TG levels in wild-type and diabetic mice (db/db), but the resulting hyperlipidemia was more significantly pronounced in the diabetic mice. While elevated plasma lipid and blood glucose levels were individually correlated with a decline in retinal function, the combination of both exacerbated retina dysfunction. This model of combined hyperglycemia and dyslipidemia can be used to dissect individual contributions of features of the metabolic syndrome to the pathogenesis of diabetic retinopathy.
This is a 2021 ARVO Annual Meeting abstract.