Health Benefits of Polyphenols and Carotenoids in Age-Related Eye Diseases

Table 2

Effects of some polyphenols on age-related eye diseases in animals.

Polyphenols	Natural source/dose/period	Cell type/animal model	Effects in chronic eye diseases	Ref
Anthocyanins	Grape skin; Asamurasaki-2 (AS2) (Japanese black rice) and chikushi-akamochi-2 (CH2) (Japanese red rice)	Sprague Dawley (SD) rat lens organ culture system	Inhibits selenite-induced cataractogenesis; Inhibitory activities for lens opacity	[79]
	Bilberry	Retinal pigment epithelium (RPE) cells	Inhibits AMD; Exhibited antioxidant activity of variable efficiency at 9 anthocyanins tested; Cells exhibited a resistance to the membrane permeabilization that occurs because of the detergent-like action of A2E	[80]
	Blueberry; STZ, 60 mg/kg; and blueberry anthocyanins at 20, 40, and 80 mg/kg were given orally, 12 weeks	Rat retinas, male rats, 5 groups; Streptozotocin-induced diabetic SD rats	It can protect retinal cells from diabetes-induced oxidative stress and inflammation, and this may be regulated through Nrf2/HO-1 signaling	[83]
	Bilberry (Vaccinium myrtillus) extract 100 mg/kg, orally, 6 weeks	Streptozotocin-induced diabetic SD rats	Prevention of diabetic retinopathy using a dietary bilberry supplement	[84]
	Seed coat of black soybean 50 mg/kg daily, orally, for 1, 2, and 4 weeks after intraperitoneal injection of N-methyl-N-nitrosourea (MNU)	Animal model of retinal degeneration; N-methyl-N-nitrosourea-induced RD rats	Reduce retinal degeneration; Anthocyanins (black soybean seeds) can protect retinal neurons from MNU-induced structural and functional damages, suggesting that it may be used as supplement to modulate RD	[85]
	Maqui berry (Aristotelia chilensis)	Murine photoreceptor cells (661 W)	Suppress the light-induced photoreceptor cell death by inhibiting ROS production; the inhibition of phosphorylated-p38 may be involved in the underlying mechanism	[86]
	Dried cornelian cherry (Cornus mas L.) polar, iridoid-polyphenol-rich fraction 1 kg of fresh fruit: 4.0 g anthocyanin of pure loganic acid; Each animal was given 0.7% loganic acid or polyphenolic fraction, intraconjunctival administration of 1 drop (50 μL)	New Zealand white rabbits, aged between 6-12 months, were used: 7 males and 7 females	Intraocular pressure (IOP)—hypotensive effect for loganic acid (0.7%)—could be compared with the widely ophthalmologically used timolol; 25% decrease in IOP was observed within the first 3 hours of use	[87]
EGCG	Green tea leaf extract (Camellia sinensis); In vivo, cataract was induced in 9-day-old rat pups by a single subcutaneous injection of sodium selenite; The treated pups were injected GTL extract intraperitoneally prior to selenite challenge and continued for 2 consecutive days thereafter; Cataract incidence was evaluated on the 16th postnatal day by slit lamp examination	Enucleated rat lenses	Inhibits selenite-induced cataractogenesis; Green tea possesses significant anticataract potential and acts primarily by preserving the antioxidant defense system	[91]
	Intraperitoneal (25 mg/kg) intraocular (5 μL of 200 μM)	Rat retinal neurons	Glaucoma prevention; It provides protection to retinal neurons from oxidative stress and ischemia/reperfusion	[93]
	20 and 40 mM	Animal models	Significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models; Treatment and prevention of ocular angiogenic diseases: age-related macular degeneration, diabetic retinopathy, and corneal neovascularization	[95]
	Nontoxic optimal concentration of EGCG used for the treatment of HCECs in vitro was 10 μg/mL IL-1β, IL-6, IL-8, and TNF-α and was significantly inhibited in inflamed HCECs treated with 10 μg/mL EGCG and 0.1% () HA (E10/HA) vs that in inflamed HCECs treated with either EGCG or HA alone	Rabbit DES model	Topical treatment with AT plus E10/HA increased tear secretion, reduced corneal epithelial damage, and maintained the epithelial layers and stromal structure; The corneas of the E10/HA-treated rabbits showed fewer apoptotic cells, lower inflammation, and decreased IL-6, IL-8, and TNF-α levels; In conclusion, we showed that AT plus E10/HA had anti-inflammatory and mucoadhesive properties when used as topical eye drops and were effective for treating DES in rabbits	[98]
Ginkgo biloba	5 μg of GBE, 4 times daily, for 14 days	Rabbits aged 7 weeks	Suppressed steroid-induced IOP elevation; it seems to prevent the adverse effects of DEX on TM cells	[100]
Quercetin	Quercetin 10 μM	Rat lens	Cataract prevention	[110]
	The expression levels of BDNF, NGF, TrkB, synaptophysin, Akt, Bcl-2, cytochrome c, and caspase-3 using Western blotting techniques with and without QCT treatments were quantitated and compared with those of nondiabetic rats; ELISA technique was used to determine the level of BDNF; Caspase-3 activity and the level of glutathione were analyzed by biochemical methods	Diabetic rat retina	Significant increase in the level of neurotrophic factors and inhibited the level of cytochrome c and caspase-3 activity; The level of an antiapoptotic protein Bcl-2 was augmented; It may protect the neuronal damage in diabetic retina by ameliorating the levels of neurotrophic factors and by inhibiting the apoptosis of neurons; Quercetin suitable therapeutic agent to prevent neurodegeneration in diabetic retinopathy	[112]
Quercetin and resveratrol	0.01% QCT, 0.1% RES, 0.01% RES (QCT + RES), or vehicle was topically applied	Desiccating stress (DS) mouse model	Reduced corneal staining in DS-exposed mice	[116]	QCT	<10^-3; <0.05
			IL-1α tear concentration was reduced by QCT, RES, and compared to mice		<0.05, 0.01, and 0.01
			CD4^+ T cells increased in recipients of DS-exposed mice and were lower in recipients of QCT- and RES-treated mice		<0.05, <0.05
			The anti-inflammatory effect of QCT, RES, and on DED experimental model suggests that their topical application could be used for DED treatment
	25 mg/kg/day quercetin by intraperitoneal injection daily, 2 months	Ccl2/Cx3cr1 double knockout (DKO) mice	Does not improve the retinal AMD-like lesions in the Ccl2/Cx3cr1 (due to its insufficient suppression of the inflammatory and apoptosis pathways in the eye)	[113]
	Quercetin 33.63 mg/kg/day and chlorogenic acid	Pigmented rabbits	AMD prevention; Its alleviating retinal degeneration	[115]	<0.05
Resveratrol	40 mg/kg; 3 groups: (1) normal saline—% 5 ethanol injected i.p. on postpartum day 10; (2) Na selenite—30 nmol/g body wt. injected s.c. on day 10; and (3) Na selenite—s.c. on day (40 mg/kg) i.p. on days 10-13	48 SD rat lens	Inhibits selenite-induced cataractogenesis; It suppressed selenite-induced oxidative stress and cataract formation in rats	[117]
	25 μM in DMSO, from Sigma, Saint Louis, MO	Porcine TM cells	Preventing or delaying of the abnormalities of the TM	[119]
	4 months oral resveratrol administration (5 mg/kg/day)	Streptozotocin-induced diabetic Wistar rats	Therapeutic supplement to prevent from diabetic retinopathy; It improves diabetic retinopathy possibly through the oxidative stress—nuclear factor kappa B—apoptosis pathway	[120]
	1 month after the 5th injection of streptozotocin or buffer—20 mg/kg, daily, for 4 weeks, and all mice were killed 2 months after the injections	Streptozotocin-induced diabetic C57BL/6 mice	Prevent diabetic retinopathy; It decreases vascular lesions and VEGF induction in mouse retinas of early diabetes	[121]
	10 mg/kg 30 days	24 streptozotocin-induced diabetic Wistar albino male rats	Prevent diabetic retinopathy; RSV suppressed the expression of eNOS, which is actively involved in the inflammation and healing process in chronic diabetes	[122]
	5 mg/kg per day for 4 months	Streptozotocin-induced diabetic Wistar albino male rats	Prevent diabetic retinopathy; Long-term resveratrol administration has beneficial anti-inflammatory properties in a rat model of diabetes	[123]
	5 and 10 mg/kg/day, 1 to 7 months	Diabetic rat retina	Prevent diabetic retinopathy; Significantly alleviated hyperglycemia and weight loss in diabetic rats; Downregulated mRNA and protein expression of GLAST and GS in diabetic rat retina was prevented	[124]