Table 4.

Studies Evaluating the Effects of Carotenoids on in vitro Models of Diabetic Retinopathy

	Author Year	Cell Lines	Carotenoids	Effects on Diabetic Retinopathy
1	Hwang, 201849	ARPE-19	Lutein	Decrease ROS levels Decrease SA-b-gal activity Increase expression and protein level of SIRT1
2	Yang, 201750	BV-2 N9	Crocin	Decrease intracellular ROS and nitrites levels Decrease expression of iNOS and COX-2 Decrease IL-1β and TNF-α levels Decrease expression of CD11b and Iba-1 Activate the PI3K/Akt signaling pathway
3	Baccouche, 201751	PRC	Astaxanthin	Enhance mitochondrial dehydrogenase activity Reduce cell apoptosis Increase positive rhodopsin photoreceptors Increase parvalbumin-positive neurons Increase NCAM positive cells
4	Umigai, 201252	HRMEC HUVEC	Crocetin	Inhibit VEGF-induced cell proliferation and migration Inhibit VEGF-induced p38 MAPK activation Decrease expression of vascular endothelial cadherin Suppress tube-like structure formation
5	Tang, 201140	ARPE-19	Zeaxanthin Lutein	Decrease ROS levels Enhance FOXO3, SOD, and thioredoxin activity Activate the AMPK signaling pathway
6	Sun, 201153	ARPE-19	Astaxanthin Lutein	Decrease ROS, RNS, and MDA levels Suppress carboxymethyllysine formation Inhibit AGE-induced cell proliferation Inhibit AGE-induced overexpression of VEGF and MMP-2
7	Kowluru, 200942	HRMEC	β-carotene	Decrease lipid peroxide levels Inhibit caspase-3 activity

Abbreviations: BV-2, microglial cells; N9, microglial cells; PRC, primary retinal cells; HRMEC, human retinal microvascular endothelial cells; HUVEC, human umbilical vein endothelial cells; ARPE-19, human adult retinal pigment epithelial cell; ROS, reactive oxygen species; RNS, reactive nitrogen species; SA-b-gal, senescence-associated b-galactosidase; SIRT1, silent information regulator 2; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; IL-1β, interleukin 1 beta; TNF-α, tumor necrosis factor alpha; PI3K/Akt, phosphoinositide-3-kinase-protein kinase/protein kinase B; NCAM, neural cell adhesion molecule; VEGF, vascular endothelial growth factor; p38 MAPK, p38 mitogen-activated protein kinases; AMPKα, AMP-activated protein kinase alpha; FOXO3α, forkhead O transcription factor 3 alpha; SOD, superoxide dismutase; AGE, advanced glycation end products; MDA, malondialdehyde; MMP-2, matrix metalloproteinase-2.