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George Heaton, Ben Davis, Lisa Turner, Shereen Nizari, Li Guo, M Francesca Cordeiro; Curcumin formulations for retinal diagnosis of Alzheimer’s disease . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2264.
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© ARVO (1962-2015); The Authors (2016-present)
Alzheimer's Disease (AD) is a devastating neurodegenerative disease.There is strong evidence to suggest that a gradual process of pathogenic accumulation of amyloid-β peptide, the primary constituent of senile plaques, occurs 10-20 years prior to symptomatic manifestation. Curcumin, the active ingredient in turmeric, is a natural fluorophore that binds with high affinity to amyloid-β and is well tolerated in humans at high concentrations. As such, using curcumin as a robust method for detecting AD associated amyloid changes is an attractive prospect. However, curcumin’s extremely low water-solubility (0.0004mg/ml) and rapid intestinal and hepatic metabolism dramatically limit its utility for oral dosage or injection. Nano-carriers such as micelles represent a means to overcome this hurdle. In this poster we present an optimised micelle formulation and freeze-drying protocol. By constructing formulations that permit effective CNS drug delivery, curcumin can bind to neurotoxic amyloid β42 associated with AD pathogenesis. Fluorescing curcumin signals can be subsequently captured through retinal imaging. We report that, following intravenous administration of curcumin-micellar solution, there is a significantly elevated retinal spot count in TASTPM transgenic murine AD model compared to age-matched wt. controls.
Micelles were prepared using thin-film lipid hydration and characterized using absorbance spectroscopy and dynamic light scattering. TASTPM transgenic mice (n=6) & age-matched 14-month C57 (n=8) were given curcumin systemically. Retinal images were acquired under general anaesthetic using an cSLO and analysed for spots via systematic blinded manual counts.
An optimised protocol produced micelles with encapsulation efficiency of 91.27±3.17%, with z-average: 21.22-23.29 and PDI: 0.032-0.169, formulations appeared homogenous over 24 hours and amenable to freeze-drying with stability at resuspension after 5 weeks. Retinal spot counts reveal a significant difference between TASTPM and age matched wild-type controls.<br /> C57: x̄= 87.625, σx̅ = 27.266, TASTPM: x̄= 145.67, σx̅ = 49.842, (P 0.02 > 0.015.)
This data offers a preliminary proof of concept study for non-invasive retinal diagnosis of AD through the use of retinal imaging. Retinal screening may represent a promising avenue towards the solution to the AD biomarker quandary.
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