Oxidative stress and its downstream signaling in aging eyes

Figures & data

Figure 1 Redox reactions and Electron-transfer. Reducing and oxidizing agents.

Figure 2 (A) Equilibrium between reactive oxygen species (ROS) production and antioxidant defense (AOX). (B) Imbalanced situation between ROS and AOX, which is associated with many pathologies.

Table 1 Oxidative stress biomarkers in primary open-angle glaucoma

Reference	Biomarker	Sample	Levels in POAG
Ames et al^Citation19	AOXT	Dietary antioxidants	↓
Zanón-Moreno et al^Citation23	MDA	Aqueous humor	↑
	AOXT	Aqueous humor	↓
Galbis-Estrada et al^Citation51	IL-6	Human tears	↑
	TNF-a	Human tears	↑
Huang et al^Citation55	CASPASES 8, 9	Rat retinal lysates and retinal whole mounts	↑
	PARP 1	Rat retinal lysates and retinal whole mounts and cross-sections	↑
Pinazo-Durán et al^Citation56	MDA	Aqueous humor	↑
	AOXT	Aqueous humor	↓
	CASPASE 3	Aqueous humor	↑
	PARP 1	Aqueous humor	↑
Saccá and Izzotti^Citation57	NO	Human trabecular meshwork	↑
	Endothelin 1	Aqueous humor	↓
Tezel et al^Citation58	GAPDH	Retinal lysates	↑
	HSP72	Retinal lysates	↑
	Glutamine synthetase	Retinal lysates	↑
Pinazo-Durán et al^Citation59	MDA	Aqueous humor	↑
	AOXT	Aqueous humor	↓
	SOD	Aqueous humor	↑
Bazán et al^Citation60	NPD 1	ARPE 19 cells	↓
Galbis-Estrada et al^Citation77	MDA	Rat retinal cross-sections, and lysates	↑
	AOXT	Rat retinal cross-sections and lysates	↓
	GSH	Rat retinal cross-sections and lysates	↓
Zanón-Moreno et al^Citation102	Vitamin E	Serum	↓
	Vitamin C	Serum	↓
	GSH Px	Serum	↓

Abbreviations: AOXT, total antioxidant activity; MDA, malondyaldehyde; IL-6, Interleukin-6; TNF-a, tumor necrosis factor-alpha; PARP-1, poly adenyl rybose polymerase-1; CS 3, caspase 3; NO, nitric oxide; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HSP72, heat shock protein 72; GSH, glutathione; SOD, superoxide dismutase; NPD 1, 10,17S-docosatriene; GSH Px, glutathione peroxidase.

Table 2 Biochemical parameters for optimal control in diabetic patients

Parameter	DM managing	Healthy population
Prepandrial plasmatic glycemia	90–130 mg/dL	70–90 mg/dL
Postpandrial plasmatic glycemia	<180 mg/dL	70–135 mg/dL
HbA1c (%)	<7%	6%
Arterial pressure	<130/80 mmHg	<140/90 mmHg
Cholesterol	<175 m/dL	<200 mg/dL
LDL	<100 mg/dL	<130 mg/dL
HDL	Man: >40 mg/dL Women: 50 mg/dL	Man: >40 mg/dL Women: >50 mg/dL
Triglycerides	<150 mg/dL	<150 mg/dL

Abbreviations: DM, diabetes mellitus; HbA_1c, glycosilated haemoglobin; LDL, low density cholesterol; HDL, high density cholesterol.

Table 3 References of glycemic index respect to the glucose (100) in main nutrients.

Bread	Glycemic index	Cereals	Glycemic index	Fruits	Glycemic index	Vegetables	Glycemic index	Dairy	Glycemic index
White bread	70	Rice	55	Watermelon	72	Carrot	71	Milk	34
Rye bread	50	Corn	55	Mango	64	Pumpkin	75	Yogurt	36
Oat bread	47	Wheat	40	Banana	53	Sweet potato	51	Ice cream	36
Macaroni	45	Chickpeas	33	Kiwi	52	Peans	48	White sugar	59
Spaghetti	35	Lentils	29	Apple	36	Potatoes	70	Fructose	20
White beans	31	Special K®	54	Pear	33	Tomatoes	38	Honey	87
Fresh beans	29	Cornflakes	85	Plum	24	Beet	64	Soja milk	18

Note: The glycemic index estimates how much each gram of carbohydrate in a particular food raises the blood glucose level following food consumption (in relation to consumption of pure glucose, which is used as the benchmark, with glucose absorption being 100% or 100).

Figure 3 (A–C) Plasma vitamin levels in primary open-angle glaucoma patients.

Table 4 Relation of clinical-epidemiological studies on the role of micronutritional supplements in age-related macular degeneration

Cited reference	Study	Findings in AMD
^Citation104	The Beaver Dam Eye Study	Inverse association between vitamins A, E and zinc intake and incidence of large drussen and macro-pigmentary changes
^Citation105	The Rotterdam Eye Study	High dietary intake of β-carotene and vitamins C, E and zinc was associated with reduced risk of AMD in the elderly
^Citation106	The Age-related Eye Disease Study (AREDS 1)	Daily intake of tablets with vitamins C, E and β-carotene, zinc and copper resulted in a moderate reduction of the risk of acquiring advanced AMD
^Citation113	The Carotenoids Age-Related Eye Disease Study (CAREDS)	Lutein- and zeaxanthin-rich diets may protect against intermediate AMD in female patients aged <75 years
^Citation114	The Australian Blue Mountains Eye Study	Intake of ω-3 fatty acids in the diet, as well as higher dietary lutein and zeaxanthin intake induced a lower incidence of developing AMD initial forms and AMD advanced forms
^Citation118	The Dietary Ancillary Study of the Eye Disease Case-Control Study (DSEDCS)	Participants with higher food intake with lutein and zeaxanthin showed a lower risk of AMD
^Citation117	The French POLA Study	Analysed the levels of antioxidant nutrients in relation to AMD. A lower rate of progression from moderate AMD to advanced AMD in one eye was found. Authors concluded that, vitamin E may provide protection against AMD
^Citation118,Citation122	The North American National Health and Nutrition Examination Survey (NHANES)	Main goal was to analyze the blood levels of vitamin E and AMD and the results showed a lesser risk of AMD initial stages with elevated levels of this vitamin
^Citation119	The Lutein and Antioxidant Supplementation study Trial (The veterans LAST)	Found a relationship between the intake of carotenoids and subjective signs of improvement of vision in 90 patients with AMD
^Citation120	The Age-Related Eye Diseases Study (AREDS 2)	Concluded and reported data on the intake of carbohydrates and the risk of suffering AMD and progression of disease, probably by oxidative damage to protein

Abbreviations: AMD, age-related macular degeneration; AREDS I, Age-Related Eye Disease Study 1; AREDS 2, Age-Related Eye Disease Study 2; CAREDS, The Carotenoids Age-Related Eye Disease Study; DSEDCS, The Dietary Ancillary Study of the Eye Disease Case-Control Study; LAST, the Lutein and Antioxidant Supplementation study Trial (The veterans LAST); NHANES, the North American National Health and Nutrition Examination Survey; POLA, the Pathologies Oculaires Liées à l’Age study.

Table 5 Combined formulation of antioxidants utilized in the 5-year follow-up study on type 2 diabetic patients and diabetic retinopathy

Vitalux forte®	ώ-3 fatty acids	Lutein/zeaxanthin	Vitamin C	Vitamin E	Zinc	Copper
Per capsule	160 mg	10 mg/1 mg	60 mg	20 mg	10 mg	0.25 mg
% recomended daily allowance	100%	100%	75%	167%	100%	25%

Note: Data from Garcia-Medina JJ, Pinazo-Duran MD, Garcia-Medina M, Zanon-Moreno V, Pons-Vazquez S. A 5-year follow-up of antioxidant supplementation in type 2 diabetic retinopathy. Eur J Ophthalmol. 2011;21:637–643.¹²⁷

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