## 4 Discussion
Besides, the eye surface may also suffer from photo-oxidative damage, and a battery of enzymatic and non-enzymatic antioxidants are present in the anterior segment of the eye to protect its structure from such damage [46]. Human corneal epithelial cells in vitro are damaged and lose viability after exposure to blue light, and such damage could be attenuated by blue light-filtering lenses [47]. Along the same line, [PERSON] and colleagues demonstrated that photooxidative damage was worsened in presence of hyperosomalic stress (as it happens in dry eye patients), thus resulting in increased inflammation and disturbed mitochondrial membrane potential, finally turning on the cell antioxidant response based on the glutathione system. Therefore, it was suggested that patients with dry eye disease could be even more sensitive to the toxicity of blue-light [48]. In fact, from a clinical perspective, it has been reported that the use of spectacles equipped with lenses able to block 50% of blue light could improve visual acuity in dry eye patients [49]. Interestingly, the irradiation source is also critical for the toxic effects on the eye. The radiation produced from organic light-emitting diodes (OLEDs) has been shown to be less toxic to ocular surface and retinal cells than the light coming from common light-emitting diodes (LEDs), most likely because of a higher blue-wavelength energy irradiated by LEDs [50]. Finally, in a mouse model, it has been shown that over-exposure to blue-violet light could cause oxidative damage and the apoptosis of corneal cells, leading to increased inflammation of the ocular surface and eventually eye dryness [12]. Intriguingly, the toxic effects of irradiation by high frequency blue light could be counteracted by lower frequency red light. It has been shown that red light irradiation stimulates mitochondrial function and increases the proliferation of human corneal epithelial cells (HCE2) in vitro, thus suggesting a possible prophylactic treatment to protect the ocular surface of dry eye patients [51]. Photo-oxidative cellular damage is closely related to a dramatic increase of ROS. Therefore, the protective efficacy of the two well-known eye-specific natural antioxidants, lutein and astaxanthin, has been here investigated. Lutein is a carotenoid with a chemical structure that gives the molecule the ability to absorb blue-violet light somewhat more efficiently than astaxanthin [52]. It has been demonstrated both in vitro and in vivo that lutein can protect the retina not only from photo-oxidative damage but also from inflammation by reducing cytokine expression levels and oxidative stress-induced apoptosis in photoreceptors [53; 54; 55]. A double-blind, placebo-controlled clinical study investigated the effects of lutein and zeaxanthin on glare disability, showing that daily supplementation with these two xanthophylls resulted in their significant increase in serum levels and in the macular region, with a parallel improvement in chromatic contrast and recovery from photostress [56]. Astaxanthin is another carotenoid, found in _Haematococcus pluvialis_, _Chloella zofingiensis_, _Chlorococcus_ and _Phaffia rhodozyma_, having anti-tumor, anti-diabetic and anti-inflammatory properties [17]. Astaxanthin, having a structure similar to lutein, can also absorb the short visible wavelengths, even though with a somewhat lower efficiency with respect to lutein. Nonetheless, astaxanthin may protect the retina from photodamage by attenuating the apoptosis of retinal ganglion cells and reducing oxidative stress [57; 58]. In fact, it is known that astaxanthin may inhibit blue-violet light LED-induced cell apoptosis and exert its protective activity through the activation of the Nrf-ARE pathway, thus increasing the expression of phase II antioxidant enzymes such as NADPH quinine oxidoreductase 1 (NQO1) and heme-oxygenase-1 (HO-1) [59; 60; 61].