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Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina
Jeremy Y Yu1, Timothy J Lyons2
1Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
Abstract:
Clinical epidemiological studies have revealed relatively weak, yet statistically significant, associations between dyslipidemia/dyslipoproteinemia and diabetic retinopathy (DR). Recent large interventional studies, however, demonstrated an unexpectedly robust efficacy of fenofibrate on the development of DR, possibly independent of plasma lipids. To unify the apparent discrepancies, we hypothesize that plasma lipoproteins play an indirect but important role in DR, contingent on the integrity of the blood-retina-barrier (BRB). In retinas with an intact BRB, plasma lipoproteins may be largely irrelevant; however, important effects become operative after the BRB is impaired in diabetes, leading to lipoprotein extravasation and subsequent modification, hence toxicity to the neighbouring retinal cells. In this hypothesis, BRB leakage is the key, plasma lipoprotein concentrations mainly modulate its consequences, and fenofibrate has intra-retinal actions. This review summarizes our current knowledge of the direct effects and mechanisms of modified lipoproteins on retinal cells and their potential contribution to the pathogenesis of DR.
Insights
Dyslipidemia is weakly linked to diabetic retinopathy (DR), but fenofibrate shows strong efficacy. This suggests lipoproteins indirectly impact DR by damaging retinal cells after blood-retina barrier breakdown in diabetes.
Area of Science:
- Ophthalmology
- Endocrinology
- Lipid Metabolism
Background:
- Clinical studies show weak associations between dyslipidemia and diabetic retinopathy (DR).
- Fenofibrate demonstrates significant efficacy in preventing DR development, independent of lipid levels.
- Existing data present a discrepancy regarding the role of lipoproteins in DR pathogenesis.
Purpose of the Study:
- To reconcile the observed discrepancies regarding dyslipidemia and DR.
- To propose a hypothesis on the indirect role of lipoproteins in DR pathogenesis.
- To review the effects of modified lipoproteins on retinal cells and their contribution to DR.
Main Methods:
- Literature review of clinical epidemiological studies and interventional trials.
- Analysis of the proposed hypothesis on the role of the blood-retina barrier (BRB).
- Summary of current knowledge on modified lipoprotein effects on retinal cells.
Main Results:
- Dyslipidemia's association with DR is statistically significant but weak.
- Fenofibrate's efficacy suggests mechanisms beyond plasma lipid reduction.
- A hypothesis is proposed where BRB integrity is crucial for lipoprotein's role in DR.
Conclusions:
- Plasma lipoproteins may indirectly contribute to DR pathogenesis.
- BRB impairment in diabetes allows lipoprotein extravasation and toxicity.
- Fenofibrate may exert intra-retinal actions, influencing DR progression.
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