**Acknowledgements**

decreased ONL, INL, and GCL thickness was also observed [86]. In STZ-induced murine models, Sasaki et al. [87] demonstrated changes in oxidative stress-related factors (increase of ROS, extracellular signal-regulated kinase activation, and depletion of brain-derived neurotrophic factor), retinal morphological changes (reduction of IPL, INL, and ganglion cells), and visual functions (decrease of oscillatory potentials in ERG, indicating dysfunction of neurons in inner retina). Likewise, lutein supplements (0.1 mg wt/wt) restored all the diabetes-induced damages in the retina [87]. Similarly, supplements containing lutein, zeaxanthin, omega-3 fatty acids, and other nutrients demonstrated protective effects on progression of DR in STZ-induced diabetic rats. Decreased ROS level, mitochondrial DNA damage, and inflammatory factors such as VEGF, IL-1β, and NF-κB, as well as reduction of retinal apoptosis, abnormal capillaries formation were demonstrated in treatment group compared with placebo control group. Furthermore, nutrient supplements ameliorated decreased amplitudes of a- and b-wave in ERG, suggesting prevention of retinal functions

Wolfberry, a Chinese traditional fruit consumed for eye protection, is high in zeaxanthin (176 mg/100 g) and lutein (5 mg/100 g). In db/db mice, wolfberry elevated lutein and zeaxanthin levels in retina and liver, attenuated mitochondrial dysfunction and endoplasmic reticulum stress caused by hyperglycemia-induced oxidative stress, and restored retinal structure abnormalities [89, 90]. Furthermore, Lutein and zeaxanthin was able to protect cultured ARPE-19 cells from a high glucose challenge through the similar mechanisms, suggesting wolfberry's protection effects were at least partly due to high contents of lutein and

Lutein, synthesized in plants but not in mammals, is absorbed and highly accumulated in the macula. The uneven distribution of lutein is thought to afford a distinct function in the retina. Up to now, numerous epidemiological studies have demonstrated that higher levels of lutein in diet and plasma are correlated with lower risk of AMD, especially the late stage of AMD. Randomized and controlled clinical trials such as AREDS2 have reported that supplementation of lutein alone or with other nutrients leads to the increase of MPOD, improvement of visual functions, and decreased risk of progression to advanced AMD, especially the wet AMD. Laboratory experimental data also indicate that lutein can protect impaired retina by filtering blue light, attenuating oxidative stress and inflammation, and enhancing neuroprotection. However, the optimal dose of lutein, the best ratio of lutein and other antioxidants, therapeutic effects at different stages of AMD, adverse effects with even longer intake of lutein supplements in high dose, and the relationship between MPOD and AMD at different phases need to be further investigated in future studies. Although there are several studies assessing the effects of lutein on DR in clinical trials and laboratory experiments, further evaluations to fully understand its protective role in DR

in diabetic rats with DR [88].

186 Progress in Carotenoid Research

zeaxanthin [89].

**6. Conclusions**

are necessary.

This work is supported by the Project of Dominant Discipline Construction in Universities of Shaanxi Province-Basic Medicine, Shaanxi Province, China awarded to Xi'an Medical University and Health and Medical Research Fund, Hong Kong (03142256) awarded to Amy C.Y. Lo.
