The results identify a select group of flavonoids that protect RPE cells from oxidative-stress-induced death with a high degree of potency and low toxicity. Many of these flavonoids also induce the expression of phase-2 detoxification proteins which could function to provide additional protection against oxidative stress. This select group of flavonoids and the foods that contain high levels of these compounds may have some clinical benefit for patients with retinal diseases associated with oxidative stress.

This report to our knowledge is the first description of the spatial distribution of A2E in the human RPE by imaging mass spectrometry. These data demonstrate that the accumulation of A2E is not responsible for the increase in lipofuscin fluorescence observed in the central RPE with aging.

These results suggest that certain flavonoids can function as potent and effective neuroprotective agents for retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non–image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs’ photoresponses. We discovered three functional ipRGC subtypes with distinct sensitivities and responses to light. The response of one ipRGC subtype appeared to depend on exogenous chromophore supply, and this response is conserved in both human and mouse retinas. Rods and cones also provided input to ipRGCs; however, each subtype integrated outer retina light signals in a distinct fashion.

Purpose Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. In the present study, we determined whether eriodictyol-induced phase II protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress. Methods We analyzed the ability of eriodictyol to activate Nrf2 and induce the phase II proteins, heme-oxygenase (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO-1), and the cellular antioxidant glutathione, (GSH). We performed cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1. We compared cell survival after short-term and long-term eriodictyol treatment and tested the mechanism of protection using a dominant negative Nrf2 and an shRNA specific for HO-1. Results We demonstrate that eriodictyol induces the nuclear translocation of Nrf2, enhances the expression of HO-1 and NQO-1, and increases the levels of intracellular glutathione. We show that ARPE-19 cells that overexpress HO-1 or NQO-1 are more resistant to oxidative stress-induced cell death than control cells. We demonstrate that eriodictyol induces long-term protection that is significantly greater than its short-term protection, and this effect is correlated temporally with both the activation of Nrf2 and the induction of phase II enzymes. We demonstrate that this effect can be blocked with the use of a dominant negative to Nrf2 and an shRNA specific to HO-1. Conclusions These findings indicate the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury.