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Daniel Hill, Vy Luong, Li Guo, M Francesca Cordeiro; In vivo Fluorescent Labelling of Retinal Amyloid Beta with Intranasal Curcumin to Detect Alzheimer’s Disease Pathology. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4072 – F0036.
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© ARVO (1962-2015); The Authors (2016-present)
A possible gateway to effective disease-modifying intervention for Alzheimer’s disease (AD) is starting treatment pre-symptomatically, facilitated by early-detection. Retinal amyloid beta (Aβ) deposition – reported to predate symptoms by over a decade – has been the subject of experiments investigating the Aβ binding compound curcumin, with controversial findings, partly attributable to the variable absorption from oral administration. Using a novel DMSO-based nasally-applied route of curcumin delivery, we hypothesised that a higher in vivo fluorescent retinal spot-count (using confocal laser scanning ophthalmoscopy) could be used to differentiate transgenic AD model mice from healthy controls, in addition to demonstrating ex vivo Aβ antibody colocalisation with curcumin.
A total of 10 triple transgenic (3xTg) AD model mice (Jackson labs) and 10 C57 control animals (Jackson labs), aged 2-6 months, were investigated. 10 µL of DMSO-based curcumin formulation was administered intranasally to awake animals. Animals’ eyes were imaged using a confocal laser scanning ophthalmoscope at baseline (before curcumin administration) and 2 hours after curcumin, under gas anaesthesia. Whole retinal mounts were immunolabelled for Aβ with the 6E10 antibody, which was fluorescently labelled with a secondary antibody. Colocalisation of nasally delivered curcumin and 6E10 antibody was studied using fluorescent microscopy.
3xTg animals appeared to have more curcumin staining than controls in vivo. Using a one-way between-subjects ANOVA, a significant (p<0.05) effect of transgenic status on spot count was found, revealing that 3xTg animals showed significantly more spots than, and could be differentiated from, healthy animals. Furthermore, histology revealed that curcumin colocalises with 6E10 antibody in the retina.
Intranasally administered curcumin appears to label retinal Aβ, and the resulting fluorescent spots can be used to identify disease state in young transgenic and healthy mice. These results suggest that such an approach may warrant further development and investigation for the early detection of AD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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