Lyons 0111

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Apolipoprotein in Diabetic Retinopathy

Principal Investigator: Timothy Lyons, MD, FRCP

Objectives:

To discern associations between plasma apolipoprotein subclasses in Type 1 diabetes compared to healthy controls and to investigate if certain apolipoprotein subclasses contribute to Diabetic Retinopathy (DR) in type 1 diabetes through exploring cell-apolipoprotein interactions in cultured retinal capillary cells.

Rationale:

Retinal capillary injury is characteristic of DR. Dyslipidemia (both quantitative and qualitative) is implicated. We previously defined associations of detailed lipoprotein characteristics, including nuclear magnetic resonance (NMR) (size-based) subclass analysis, with retinopathy in Diabetes Control and Complications Trial (DCCT). We also demonstrated that exposure of retinal capillary cells to glycated and oxidized lipoproteins, as found in diabetes, stimulates altered signaling, gene expression, and apoptosis, potentially contributing to DR. Apolipoprotein-based subclass analysis has never been performed in Type 1 diabetes, nor related to retinopathy status or to other lipoprotein characterizations. The interactions between subclasses and cultured retinal capillary cells are unknown.

Hypotheses:

Apolipoprotein-based lipoprotein subclass profiles associated with Type 1 diabetes may determine susceptibility to DR.

Specific Aims:

1. To determine differences in apolipoprotein-based lipoprotein profiles in Type1 diabetic patients versus healthy controls.

2. To investigate relationship between apolipoprotein-based profiles and other lipoprotein characteristics (conventional lipid profiles, NMR), inflammatory markers.

3. To explore effects of individual apolipoprotein-defined subclasses, isolated from fresh blood samples, on retinal capillary pericytes.

Methods:

Patients will be recruited from the patient cohort attending our diabetes clinics. All methods for apolipoprotein subclass determination and data analysis are in place.

Participant Inclusion Criteria:

Participant Compensation:

Contact Information:

Yong “Jeremy” Wu. (405) 271-5896 X 48466 or yong-wu@ouhsc.edu

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