Reactive Oxidation Species and Antioxidants

Question 1

What antioxidant does the lens use to combat oxidative stress

Answer 1

Enzymes glutathione reductase, GSH-Px, catalase, and SOD

Question 2

What vision threatening diseases are associated with oxidative stress

Answer 2

cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration

Question 3

What study confirmed the role of antioxidants in slowing progression of AMD

Answer 3

AREDS- Age-Related Eye Disease Study

Question 4

What is the function of ROS under normal physiologic conditions

Answer 4

reactive oxygen species (ROS) participate in normal biochemical processes, where they either act as intermediaries or function as second messengers. Also, ROS can be generated by exogenous influences, such as exposure to ultraviolet (UV) light or cigarette smoking. Oxidative stress occurs when the production of ROS exceeds their degradation

Question 5

How are ROS generated

Answer 5

from metabolic processes, inflammatory responses, and exposure to UV light

Question 6

Examples of ROS

Answer 6

hydrogen peroxide (H2O2) and singlet oxygen (1O2), as well as lipid peroxides and reactive carbohydrates such as ketoamine and ketoaldehyde groups. Free radicals, another group of ROS, possess an unpaired electron that makes them highly reactive toward other molecular species

Question 7

What are exogenous sources of ROS

Answer 7

UV light and tobacco smoke

Question 8

What are endogenous sources of ROS

Answer 8

electron transport chain in mitochondria and, as part of our innate immune response by neutrophils and macrophages, respiratory burst, where superoxide anion (O −) 2 and the hydroxyl radical (OH) form to attack pathogens. The nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) constitute an enzyme family that functions primarily to produce ROS and is expressed in many cells

Question 9

How does ROS lead to cell death

Answer 9

Apoptosis. Can also occur through loss of the barrier function of the plasma membrane via a process known as lipid peroxidation

Question 10

What pathways are involved in eliminating ROS

Answer 10

1) glutathione peroxidase; (2) catalase; and (3) peroxidase

Question 11

ROS- Superoxide anion (O2-). What is the source and antioxidants involved in detoxification

Answer 11

Source: electron transport chain (mitochondria), respiratory burst (neutrophils), xanthine oxidase
Antioxidants: Superoxide dismutase (SOD)

Question 12

ROS- Hydroxyl radical (OH.). What is the source and antioxidants involved in detoxification

Answer 12

Source: electron transport chain (mitochondria), respiratory burst (neutrophils)
Antioxidants: Catalase and peroxidase

Question 13

ROS- hydrogen peroxide (h2O2). What is the source and antioxidants involved in detoxification

Answer 13

Source: electron transport chain (mitochondria), respiratory burst (neutrophils), superoxide dismutase
Antioxidants: Catalase and Peroxidas, glutathione peroxidase

Question 14

ROS- Singlet oxygen (1O2). What is the source and antioxidants involved in detoxification

Answer 14

Source: Photo-oxidation
Antioxidants: Carotenoids (quenching)

Question 15

How does lipid peroxidation occur

Answer 15

3 steps- initiation, propagation and termination.
Initiation- fatty acids converted to intermediate radical due to loss of one hydrogen. This reacts with oxygen to form peroxidase radical. ROO. This is called lipid peroxidation

Question 16

Example of free radical scavenger

Answer 16

Vitamin E

Question 17

How can photooxidation be inhibited

Answer 17

O2 quenching carotenoids

Question 18

What structures can lipid peroxidation damage

Answer 18

Retina and Lens

Question 19

Defense mechanism from ROS

Answer 19

UV light exposure protection by cornea and lens. High ascorbate (vitamin C) content of the aqueous and vitreous. Enzymes which neutralise ROS eg Superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase

Question 20

What is the mechanism of damage in siderosis bulbi and haemosiderosis bulbi

Answer 20

Formation of h2O2 by free iron (Fe2+) is the mechanism underlying damage to structures in the eye in siderosis bulbi and hemosiderosis bulbi. the former is due to iron released into the eye from a retained intraocular foreign body; the latter, from the breakdown of hemoglobin molecules in cases of intraocular hemorrhage. In both conditions, excess Fe2+ can accumulate in the trabecular meshwork, neurosensory retina, and retinal pigment epithelium (RPE), leading to secondary dysfunction

Question 21

How is most UVB radiation absorbed in the eye

Answer 21

(<320-nm wavelength) striking the human eye is absorbed either by the cornea or by the ascorbate present at high levels in the aqueous humor, a certain amount reaches the lens epithelium, where it can cause damage. UVA light (320–400-nm wavelength) can penetrate more deeply into the lens, where it can react with various chromophores to generate H O , O *−, and 1O .

Question 22

What is the purpose of sulfhydryl groups in the lens

Answer 22

The lens contains unusually high levels of protein sulfhydryl groups that must exist almost entirely in the reduced state for the tissue to remain transparent

Question 23

Which antioxidant in the lens acts as a major scavenger of ROS

Answer 23

Glutathione (GSH), concentrated at the lens epithelium. Studies have indicated that a cortical–nuclear barrier may exist in the mature human lens, which inhibits the free flow of GSH to the nucleus. As a result, the human lens nucleus becomes more susceptible to oxidative damage and cataract formation with age.

Question 24

What did the AREDS, AREDS2 and VECAT trial show with regards to cataracts

Answer 24

found that high-dose formulations of antioxidants neither prevented the development nor slowed the progression of age-related cataracts.

Question 25

Impact on retinal photoreceptors when exposed to oxidative challenges

Answer 25

Experimental data have shown that retinal photoreceptors degenerate when exposed to oxidative challenges such as hyperbaric oxygen, iron overload, or injection of lipid peroxide into the vitreous humor. In addition, the retina degenerates when antioxidant defenses are reduced

Question 26

Characteristics of the retina increasing its susceptibility to damage from lipid peroxidation

Answer 26

1) Vertebrate rod outer segments susceptible due to high levels of PUFA’s. Phospholipids contain docosahexaenoic acid, highly polyunsaturated
2) Rod inner segments rich in mitochondria. Majority of endogenous ROS produced by mitochondrial electron transport chain leaking activates ROS
3) Abundant oxygen supply in choroid and retina vessels increases risk of oxygen damage
4) Many chromophores in outer retina. Light exposure may trigger photo oxidative processes mediated by 1O2

Question 27

What antioxidants are found in vertebrate retinas and RPE

Answer 27

1) Selenium
2) GSH
3) Selenium dependent GSH-Px
4) Non selenium dependent GSH-Px (glutathione S transferase)
5) Vitamin E
6) SOD
7) Catalase
8) Carotenoids

Question 28

Where is the highest concentration of selenium in the human eye found

Answer 28

RPE. Levels in retina remain constant but increase with age in RPE

Question 29

What does superoxide dismutase SOD do?

Answer 29

Catalyzes the dismutation of superoxide to H2O2 which is further reduced to water by catalase or peroxidase

Question 30

What is the precursor of vitamin A

Answer 30

Beta carotene

Question 31

What makes up the yellow pigment at the macula

Answer 31

Studies of postmortem human retinas have shown that carotenoids make up the yellow pigment in the macula. Two carotenoids, lutein and zeaxanthin, are present in the macula and located in the Henle fiber layer

Question 32

Where is zeaxanthin and lutein mainly found

Answer 32

In humans, zeaxanthin is concentrated primarily in the fovea, whereas lutein is dispersed throughout the retina

Question 33

Where are carotenoids found in the eye

Answer 33

Carotenoids are present only in the retina and are absent from the RPE. In the peripheral retina, lutein and zeaxanthin are concentrated in rod outer segments and may act as antioxidants to protect against short- wavelength visible light

Question 34

Where are vitamin E and selenium primary found

Answer 34

RPE

Question 35

Which metabolic pathways are implicated in the development of diabetic retinopathy

Answer 35

• polyol pathway
• protein kinase C (PKC) pathway
• hexosamine pathway

Question 36

What risk factors related to oxidative mechanisms are found in AMD

Answer 36

sunlight exposure, smoking, and to some extent genetics

Question 37

What did the AREDS and AREDS2 trial show with regards to antioxidants and their role in AMD

Answer 37

both trials supported the role of antioxidants in limiting the progression of AMD in high-risk patients