Table 3.

Studies Evaluating the Effects of Carotenoids on Retinal Tissue of Diabetic Animal Models

	Author, Year	Animal Models	Carotenoids	Effects on Diabetic Retinopathy
1	McClinton, 201935	STZ-induced diabetic rat	Carotenoid-rich diet	Aggravate a- and b-wave amplitude in electroretinography Aggravate a-, OP- and b-wave latency in electroretinography
2	Sharavana, 201736	STZ-induced diabetic rat	Lutein	Increase GSH levels and SOD activity Decrease carbonyl and MDA levels Decrease expression of VEGF and VEGF receptor Decrease co-receptor and transcription factor of VEGF receptor Decrease hypoxia-inducible factor Prevent RGC loss and maintain INL thickness
3	Yeh, 201637	STZ-induced diabetic rats	Astaxanthin Lutein	Decrease 8-OHdG, nitrotyrosine and acrolein levels Enhance hemeoxygenase, peroxiredoxin and thioredoxin activity Decrease NF-kB levels Decrease MCP-1, fractalkine and ICAM-1 levels Prevent RGC loss and maintain TR, IPL, INL, and ORL thickness Restore b-wave amplitude in electroretinography
4	Kowluru, 201438	STZ-induced diabetic rats	Lutein, zeaxanthin-rich diet	Decrease ROS and increase total antioxidant capacity Decrease VEGF, NF-kB, IL-1β levels Reduce mitochondrial DNA damages Reduce capillary cell apoptosis Restore a- and b-wave amplitude in electroretinography
5	Yu, 201339	Transgenic diabetic mice	Zeaxanthin, Lutein-rich wolfberry diet	Enhance expression of TFAM and PCG-1 Decrease expression of hypoxia-inducible factor, VEGF and HSP60 Enhance expression of AMPK
6	Tang, 201140	Transgenic diabetic mice	Zeaxanthin, Lutein, Cryptoxanthin-rich wolfberry diet	Enhance expression of thioredoxin, SOD and FOXO3α Decrease BiP, PERK, ATF6, caspase-3 and caspase-12 levels Enhance activation of AMPK Suppress capillary-like structure formation Decrease disorganized nuclear distribution in the ONL Prevent RGC loss and restore RPL and INL thinking
7	Sasaki, 201041	STZ-induced diabetic mice	Lutein-rich diet	Decrease ROS levels Increase BDNF and synaptophysin levels Inhibit activation of ERK signaling pathway Reduce cell apoptosis and caspase-3 levels Prevent RGC loss and maintain INL and IPL thickness Restore OP amplitude in electroretinography
8	Kowluru, 200943	Alloxan-induced diabetic rats	β-carotene-containing supplement	Decrease NF-kB levels Decrease expression of iNOS Decrease lipid peroxides, nitrotyrosine and NO levels
9	Kowluru, 200942	Alloxan-induced diabetic rats	β-carotene-containing supplement	Decrease lipid peroxides Inhibit activation of caspase-3
10	Arnal, 200944	STZ-induced diabetic rats	Lutein	Decrease MDA and nitrotyrosine levels Enhance glutathione peroxidase activity and GSH levels Reduce apoptosis Prevent RGC loss and maintain INL ONL, and TR thickness Restore b-wave amplitude and latency in electroretinography
11	Kowluru, 200845	STZ-induced diabetic rats	Carotenoid-rich diet	Decrease Lipid peroxide, nitrotyrosine, and 8-OHdG level No beneficial effect on GSH levels Decrease expression of iNOS Increase expression of SOD and mitochondrial complex III Decrease VEGF and ICAM-1 levels
12	Kowluru, 200845	STZ-induced diabetic rats	Carotenoid-rich diet	Decrease nitrotyrosine and 8-OHdG level Increase expression of SOD and catalase Increase expression of iNOS and mitochondrial complex III Decrease acellular capillaries
13	Muriach, 200647	Alloxan-induced diabetic mice	Lutein	Decrease MDA and NF-kB levels Increase GSH levels and glutathione peroxidase activity Restore b-wave amplitude in electroretinography
14	Dene, 200548	STZ-induced diabetic rats	β-carotene	No beneficial effect on gamma-glutamyltransferase activity Increase glutathione reductase activity
15	Kowluru, 200146	STZ-induced diabetic rats	β-carotene-rich diet	Decrease glutamate levels Decrease lipid peroxides and NO levels

Abbreviations: GSH, reduced glutathione; MDA, malondialdehyde; VEGF, vascular endothelial growth factor; RGC, retinal ganglion cell; TR, total retina; IPL, inner plexiform layer; INL, inner nuclear layer; ORL, outer retinal layers; RPL, retina photoreceptor layer; OP, oscillatory potential; 8-OHdG, deoxyguanosine; ICAM-1, intercellular adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1; NF-kB, nuclear factor kB; ROS, reactive oxygen species; IL-1β, interleukin 1 beta; HSP60, heat shock protein 60; AMPKα, AMP-activated protein kinase alpha; BiP, binding immunoglobulin protein; PERK, protein kinase RNA-like ER kinase; ATF6, activating transcription factor 6; SOD, superoxide dismutase; FOXO3α, forkhead O transcription factor 3 alpha; TNF-α, tumor necrosis factor alpha; BDNF, brain-derived neurotrophic factor; NO, nitric oxide; iNOS, inducible nitric oxide synthase; ERK, extracellular signal-regulated kinases.