**Acknowledgements**

wolfberry can alleviate the Aβinduced degenerative process by promoting survival signals, suppressing ER stress, reducing glutamate excitotoxicity [103]-[107]. In rat glaucoma model, wolfberry shows its beneficial effects on the retina based on suppressing neurodestructive factors, modulating the inflammatory responses [108], and up regulating the expression of protective chaperone – crystallin [109]. The neuroprotective effects of wolfberry shared between AD and glaucoma further strengthen our hypothesis that knowledge obtained from

On the other hand, retina can be a promising platform to investigate the efficacy of any potential drugs on different neuronal cells. In the study of rat chronic glaucomatous model, immunotherapy with a potential agent such as β-secretase inhibitor, Congo Red or Aβ antibody successfully reduced Aβ-induced RGC apoptosis by suppressing further Aβ aggregation and inhibiting the enzymatic activity of amyloidogenesis [81]. In APPswe/PS1ΔE9 mice, following MOG45D-loaded dendritic cells immunization, Aβ−plaque burden in the

In a recent study using APPswe/PS1ΔE9 mice with five days of systemic administration of curcumin, the results showed that there is a age-dependent correlation between plaque deposition in the retina and the brain, and increased accumulations over the course of disease progression [52]. This is the very first prove that Aβ plaques in the retina pre‐ cede the existence of brain plaques. The Aβ plaques can be detected as early as 2.5 months of age in the retina but Aβ plaques in the brain exists at the age of 5 months, which is about 2 months later [110]. Curcumin is a natural and safe fluorochrome that binds and labels Aβ plaques [111], [112]. In a six-month randomized, placebo-controlled, doubleblind, pilot clinical trial in AD patients, there was no significant side effects even when

Early sign of AD symptoms in the brain can hardly be detected. With the use of curcumin, retinal degeneration may be the most important site to be studied in early AD pathology. Future development of high-resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies can be achieved non-invasively through direct imaging of the retina. Progression of therapy is possible to be visualized qualitatively in a sense that one can monitor the changes of a particular neuronal cell [114], [115]. Quantitative examination of the disease stages have been performed by assessing the ratio of apoptosis to necrosis using fluorescence counts of respective dyes [74]. Even more, a high spatial resolution of images with a high signal-to-noise ratio ranging from 3:1 to 10:1 can be achieved with the imaging of the retina [114], [115]. The merits of non-invasive retinal imaging can provide investigators a solid support for assessing pathological status as well as developing and refining therapeutic strategies. Considering the potential of direct optical imaging of the retina, especially the Aβ plaques deposition in the retina labeled by curcumin, retinal degeneration in early AD is the

window of monitoring disease progression as well as effectiveness of treatment.

With all the findings we pointed out in this review, we can formulate our working hypothesis for researchers: increase in the level of Aβ or hyperphosphorylated tau protein may be the copathological factors of glaucoma leading to progressive neurodegeneration in the retina.

the brain can be transferred to the study of the retina.

168 Glaucoma - Basic and Clinical Aspects

retinas was reduced as effective as that in the brain [52].

patients took curcumin at the dose of 4 g/day [113].

Research in this laboratory is partly supported by HKU Alzheimer's Disease Research Network under Strategic Research Theme on Healthy Aging. The authors declare that we do not have competing interest in this review.
