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Theses, Ph.D


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Successfully submitted for the award of PhD.


The macula is a specialised part of the retina responsible for detailed central and colour vision. The carotenoids lutein, zeaxanthin and meso-zeaxanthin are uniquely concentrated in the inner and central layers of the primate macula, where they are collectively known as macular pigment (MP). Macular pigment confers potent antioxidant and anti-inflammatory effects in the eye. Many studies have suggested that these carotenoids are lower in age-related macular degeneration (AMD) and that increased levels of MP may confer protection against AMD, especially the late form of the disease. Research is now beginning to focus on MP optical density (MPOD) and carotenoid intake in diabetes mellitus, a condition which similar to AMD, is known to cause oxidative damage and inflammation in the retina. Methods The optical density of MP was measured in a group of participants with diabetes (Type 1 and Type 2) and findings compared with normal healthy controls. A comprehensive review was performed to investigate the putative causal mechanisms and metabolic perturbations associated with lower MP in diabetes. Surrogate biomarkers for the prediction of low MP in participants with Type 2 diabetes and older adults free of ocular pathology, including clinical [blood pressure], plasma [lipoproteins, inflammatory markers] and anthropometric [waist (cm), hip (cm), height (cm), weight (kg)] parameters, were investigated and identified as part of a large randomly selected sample from the Republic of Ireland (as part of The Irish Longitudinal Study on Ageing [TILDA]). 2 Results The optical density of MP was lower among Type 2 diabetes subjects (0.33 ± 0.21) compared with Type 1 subjects (0.49 ± 0.23) and normal controls (0.48 ± 0.35) (p= 0.01). A comprehensive review of MP and diabetes, Type 2 diabetes, in particular, revealed that MP may become depleted through at least four possible causal mechanisms in this condition including overweight/obesity, dyslipidaemia, oxidative stress and inflammation. Research performed on the TILDA cohort confirmed that participants with Type 2 diabetes had significantly lower MPOD compared with non diabetic controls (p=0.047). In-depth analysis on this Type 2 diabetes cohort revealed that MP was significantly lower in diabetes participants who were deficient in plasma vitamin D (/L) (p=0.006); who had a raised triglyceride (TG) over high density lipoprotein (HDL) ratio (TG/HDL) [>1.74 mmol/L; p=0.039]; who had hypertension (p=0.043); who were current smokers (p=0.022); or who had cataracts (p=0.049). Among older adults who were free of ocular pathology (i.e. AMD, glaucoma, diabetes, pre-diabetes), MPOD was significantly lower among participants with an elevated waist circumference (WC) (p=0.034), those who had low plasma HDL (p=0.038), those with a raised plasma TG/HDL ratio (p=0.003) and those with a raised total cholesterol (TC) over HDL ratio (TC/HDL) (p=0.030). Conclusion Overall, our findings suggest that individuals with Type 2 diabetes have lower MP relative to healthy controls. The metabolic correlates associated with Type 2 diabetes, in particular, i.e. oxidative stress, inflammation, overweight/obesity and dyslipidaemia, may have important implications for MPOD in the retina. Surrogate biomarkers associated with lower MP in Type 2 diabetes include low plasma levels of 3 vitamin D (25(OH) D), dyslipidaemia (i.e. raised TG/HDL ratio), hypertension, cataracts and smoking. While an altered lipoprotein profile (i.e. low HDL, raised TG/HDL ratio, raised TC/HDL ratio), may affect the transport, uptake, and stabilisation of carotenoids in the retina of older adults free of ocular pathology, it appears that WC is a more robust predictor of lower MPOD in this patient cohort. However, its effect size appears to be small and therefore its clinical applicability is questionable.

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