Every component of the eye is vulnerable to damage from ROI, particularly retina. There are several reasons for the vulnerability of the retina, including high concentrations of polyunsaturated fatty acid (PUFA), constant exposure to visible light, high consumption of oxygen, an abundance of photosensitisers in the neurosensory retina and the RPE, the process of phagocytosis by the RPE which is known to generate hydrogen peroxide.
Fungal infections of eye cause one of the most dangerious infections. Accurate diagnosis and proper institution of anti-fungal therapy is essential. Here we discuss the various anti-fungal agents available to be used in ophthalmology.
Types of fat, transportation of fat in the blood, FUnction of fat in the diet, DHA accumulation in the eye, Disc shedding in the retina, DHA conservation in eye, Role of DHA in the eye
Fungal infections of eye cause one of the most dangerious infections. Accurate diagnosis and proper institution of anti-fungal therapy is essential. Here we discuss the various anti-fungal agents available to be used in ophthalmology.
Types of fat, transportation of fat in the blood, FUnction of fat in the diet, DHA accumulation in the eye, Disc shedding in the retina, DHA conservation in eye, Role of DHA in the eye
INTRODUCTION
WHEN A NORMAL INDIVIDUAL FIXES HIS VISUAL ATTENTION ON AN OBJECT OF REGARD ,THE IMAGE IS FORMED ON THE FOVEA OF THE BOTH EYES SEPARATELY ,BUT THE INDIVIDUAL PERCEIVES A SINGLE IMAGE .
BINOCULAR SINGLE VISION CONSIST OF 3 GRADES :
SIMULTANEOUS MACULAR PERCEPTION
FUSION
STEREOPSIS
SIMULTANEOUS MACULAR PERCEPTION :
POWER TO SEE TWO DISSIMILAR OBJECTS SIMULATANEOUSLY
FUSION :
POWER TO SUPERIMPOSE TWO INCOMPLETE BUT SIMILAR IMAGES TO FORM ONE COMPLETE IMAGE
STEREOPSIS :
ABILITY TO PERCEIVE THE 3RD DIMENSION (DEPTH PERCEPTION )
Management of visual problems of Aging by Ashith Tripathi Ashith Tripathi
This presentation contains headings - Visual performance in the ageing eye
Routine optometric and ocular examination of an older adult:
History
Ocular health examination
Visual acuity measurement
Refraction
Binocular vision
Visual field measurement
Colour vision
Management of vision problems in older adults
Frame requirement
Lens requirements
And special instructions etc.
in this presentation, the light is focused on discussing the Reactive oxygen species, oxidative stress, how it forms, how it affects the body and what are the diseases that correlate with oxidative stress.
nevertheless, how it can be balanced by the antioxidants and what is their role in oxidative stress.
INTRODUCTION
WHEN A NORMAL INDIVIDUAL FIXES HIS VISUAL ATTENTION ON AN OBJECT OF REGARD ,THE IMAGE IS FORMED ON THE FOVEA OF THE BOTH EYES SEPARATELY ,BUT THE INDIVIDUAL PERCEIVES A SINGLE IMAGE .
BINOCULAR SINGLE VISION CONSIST OF 3 GRADES :
SIMULTANEOUS MACULAR PERCEPTION
FUSION
STEREOPSIS
SIMULTANEOUS MACULAR PERCEPTION :
POWER TO SEE TWO DISSIMILAR OBJECTS SIMULATANEOUSLY
FUSION :
POWER TO SUPERIMPOSE TWO INCOMPLETE BUT SIMILAR IMAGES TO FORM ONE COMPLETE IMAGE
STEREOPSIS :
ABILITY TO PERCEIVE THE 3RD DIMENSION (DEPTH PERCEPTION )
Management of visual problems of Aging by Ashith Tripathi Ashith Tripathi
This presentation contains headings - Visual performance in the ageing eye
Routine optometric and ocular examination of an older adult:
History
Ocular health examination
Visual acuity measurement
Refraction
Binocular vision
Visual field measurement
Colour vision
Management of vision problems in older adults
Frame requirement
Lens requirements
And special instructions etc.
in this presentation, the light is focused on discussing the Reactive oxygen species, oxidative stress, how it forms, how it affects the body and what are the diseases that correlate with oxidative stress.
nevertheless, how it can be balanced by the antioxidants and what is their role in oxidative stress.
Oxidative stress is the main metabolic process that causes mitochondrial dysfunction. In this presentation we show different oxidative stress pathways and the main solutions to prevent mitochondrial damage by using non enzymatic antioxidants and boosting antioxidant enzymatic systems.
Free radicals in human diseases and the roleMohammed Sakr
Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Free radicals are a main cause of cardiovascular diseases, cancer, aging and immune defense disorders. Foods like berries and carrot protect us against free radicals.
Free radical reactions are expected to produce progressive adverse changes that accumulate with age throughout the body. Such “normal” changes with age are relatively common to all.
However, superimposed on this common pattern are patterns influenced by genetics and environmental differences that modulate free radical damage.
These are manifested as diseases at certain ages determined by genetic and environmental factors.
Cancer and atherosclerosis, two major causes of death, are salient “free radical” diseases. Cancer initiation and promotion is associated with chromosomal defects and oncogene activation. It is possible that endogenous free radical reactions, like those initiated by ionizing radiation, may result in tumor formation.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
An enzyme is a substance that acts as a catalyst in living organisms, regulating the rate at which chemical reactions proceed without itself being altered in the process. The biological processes that occur within all living organisms are chemical reactions, and most are regulated by enzymes
The aqueous humour is a transparent, watery fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary epithelium, a structure supporting the lens
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. The cornea, with the anterior chamber and lens, refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power.
Lens is a transparent, biconvex, crystalline structure placed between iris and the vitreous in a saucer-shaped depression, the patellar fossa. The lens is a crystalline structure that is avascular and is devoid of nerves and connective tissue
It consists of three distinct part:
Lens capsule
Anterior lens epithelium, and
Lens substance or lens fibres
Small amounts of vitamins are required in the diet to promote growth, reproduction, and health. Vitamins A, D, E, and K are called the fat-soluble vitamins, because they are soluble in organic solvents and are absorbed and transported in a manner similar to that of fats.
Water soluble vitamins include Vitamin C and the vitamin B complex: thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), Vitamin B6, biotin (B7), folic acid (B9), Vitamin B12. Vitamin A in its Beta-Carotene form is also water-soluble.
The tear film is a complex mixture of substances secreted from multiple sources on the ocular surface, including the lacrimal gland, the accessory lacrimal glands, the meibomian glands, and the goblet cells.
A picornavirus is a virus belonging to the family Picornaviridae, a family of viruses in the order Picornavirales. Vertebrates, including humans, serve as natural hosts. Picornaviruses are nonenveloped viruses that represent a large family of small, cytoplasmic, plus-strand RNA viruses with a 30-nm icosahedral capsid.
Poxviruses are brick or oval-shaped viruses with large double-stranded DNA genomes. Poxviruses exist throughout the world and cause disease in humans and many other types of animals. Poxvirus infections typically result in the formation of lesions, skin nodules, or disseminated rash.
Leptospirosis is a bacterial disease that affects humans and animals. It is caused by bacteria of the genus Leptospira. In humans, it can cause a wide range of symptoms, some of which may be mistaken for other diseases. Some infected persons, however, may have no symptoms at all.
The human immunodeficiency virus (HIV) is a lentivirus (a subgroup of retrovirus) that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS).
Treponema is a genus of spiral-shaped bacteria. The major treponeme species of human pathogens is Treponema pallidum, whose subspecies are responsible for diseases such as syphilis, bejel, and yaws.
Haemophilus is the name of a group of bacteria. There are several types of Haemophilus. They can cause different types of illnesses involving breathing, bones and joints, and the nervous system. One common type, Hib (Haemophilus influenzae type b), causes serious disease. It usually strikes children under 5 years old
Moraxella is a genus of Gram-negative bacteria in the Moraxellaceae family. It is named after the Swiss ophthalmologist Victor Morax. The organisms are short rods, coccobacilli, or as in the case of Moraxella catarrhalis, diplococci in morphology, with asaccharolytic, oxidase-positive, and catalase-positive properties
Pseudomonas is a type of bacteria that can cause infections. Pseudomonas is a common genus of bacteria, which can create infections in the body under certain circumstances. There are many different types of Pseudomonas bacteria
Neisseria gonorrhoeae is the obligate human pathogen that causes the sexually transmitted disease (STD) gonorrhea. This Gram-negative diplococci/gonococci does not infect other animals or experimental animals and does not survive freely in the environment. The gonococcal infection occurs in the upper or lower tract, pharynx, ophthalmic area, rectum, and bloodstream. During the 1980’s gonorrhea was also referred to as “the clap” when public awareness was quite minimal. This was one of the venereal diseases prostitutes hoped to contract since it resulted in infertility by pelvic inflammatory disease (PID). As documentation, diagnostic testing, and public awareness improved, there has been a decline in incidence reports, however, it is still considered a very common infectious disease.
Meningococci are a type of bacteria that cause serious infections. The most common infection is meningitis, which is an inflammation of the thin tissue that surrounds the brain and spinal cord. Meningococci can also cause other problems, including a serious bloodstream infection called sepsis. In its early stages, you may have flu-like symptoms and a stiff neck. But the disease can progress quickly and can be fatal. Early diagnosis and treatment are extremely important. Lab tests on your blood and cerebrospinal fluid can tell if you have it. Treatment is with antibiotics. Since the infection spreads from person to person, family members may also need to be treated.
A vaccine can prevent meningococcal infections.
Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Diphtheria causes a thick covering in the back of the throat. It can lead to difficulty breathing, heart failure, paralysis, and even death. CDC recommends vaccines for infants, children, teens and adults to prevent diphtheria. The presentation consists of basic concepts regarding the bacteria and its infection. It has explanation in detail about signs and symptoms of Diptheria
Contraindications, Adverse reactions and ocular nutritional supplementsArun Geetha Viswanathan
utritional supplements comprise a great deal of the products available over the counter in most pharmacies. Although most vitamin supplements are relatively harmless—except for the fat soluble ones A, D, E, and K—they are not the only supplements available to patients. Some of these other, non-vitamin supplements can actually be harmful to patients and often they have been proven to be ineffective. This doesn’t mean that patients will stop taking them though, which in turn leaves the potential for contraindications of nutritional supplements with prescription-based drugs wide open.
Ageing is a gradual process that takes place over many decades. Most theories of ageing relate to impaired DNA replication and loss of cell viability and hence the viability of the body’s organs. Ageing is often accompanied by socioeconomic changes that can have a great impact on the nutritional needs and status of elderly individuals. The incidence of disability increases with ageing, with over a third of the elderly population limited by chronic conditions and unable to carry on normal daily living activity
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Multi-source connectivity as the driver of solar wind variability in the heli...
Oxidative stress and the eye
1. Unit: IV
Minerals and trace elements and eye
Carotenoids and eye
Oxidative stress and the eye
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)
2. Unit: IV
Oxidative stress and the eye
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)
3. Oxidative Processes
• oxidation refers to the removal of electrons, and reduction refers to the gain of
electrons
• TCA cycle is responsible for most of the oxidation of dietary carbohydrates, proteins
and lipids to CO2 and H2O
• The energy yielded is conserved in the form of the reduced electron accepting
coenzymes, nicotinamide adenine dinucleotide (NADH) and flavin adenine
dinucleotide (FADH2)
• The electrons of these coenzymes can be used to reduce O2 to H2O via the
electron transport chain, and this reaction releases energy for the conversion of
ADP and Pi to ATP in a process known as phosphorylation.
4. Oxidative Processes
• Oxidative phosphorylation occurs in the mitochondrion and is catalysed by ATP
synthase
• The electron transport chain accounts for approximately 90% of our total O2
consumption, the remainder being utilised by reactions involving oxidases or
oxygenases
• The majority of ROI are formed during energy generation from mitochondria, or
during the detoxifying reactions involving the liver cytochrome P450 enzyme
system
5. Reactive Oxygen Intermediates
• Most ROI are the inevitable byproducts of normal and essential metabolic reactions,
such as energy generation from mitochondria
• Pollution
• Asbestos
• fungal or viral infections
• Cigarette smoking
• Excess consumption of alcohol
• Irradiation (mainly blue wavelength light)
• Inflammation and ageing are all known to be associated with increased production
of ROI.
6. Reactive Oxygen Intermediates
• ROI can be classified according to their reactivity towards biological targets, their
site of production, their chemical nature, or their free radical or non-radical
subgroups
7. Reactive Oxygen Intermediates
• Free radicals are molecules that
contain one or more unpaired
electrons in their outer orbits
• In order to achieve a stable state, free
radicals extract electrons from other
molecules, which are themselves
rendered unstable by this interaction,
and a cytotoxic oxidative chain
reaction results
• Non-radical ROI contain their full
complement of electrons, but in an
unstable state
• The most important among them is
hydrogen peroxide and singlet oxygen
• Hydrogen peroxide can generate free
radicals through the Fenton reaction and
singlet oxygen can damage molecules as
it converts back to normal oxygen.
8. ROI and Cellular Damage
Every component of the eye is vulnerable to damage from ROI – particularly retina
There are several reasons for the vulnerability of the retina, including
1. high concentrations of polyunsaturated fatty acid (PUFA)
2. constant exposure to visible light
3. high consumption of oxygen
4. an abundance of photosensitisers in the neurosensory retina and the RPE
5. the process of phagocytosis by the RPE, which is known to generate hydrogen
peroxide.
9. ROI and Cellular Damage
• The high concentrations of PUFA (50%) are found in the lipid bilayer of the outer
segment of the rod photoreceptors, and DHA accounts for approx. 50% of the
vertebrate rod photoreceptor phospholipids
• The susceptibility of an unsaturated fatty acid to oxidation correlates directly with
the number of its double bonds
• PUFAs are particularly susceptible to free radical damage because their conjugated
double bonds are convenient sources of hydrogen atoms, which contain one
electron
• The lipid radical thus formed then combines with oxygen to form lipid peroxyl
radicals and lipid peroxides, which can only be stabilised by acquiring a quenching
electron, probably from an adjacent PUFA.
10. ROI and Cellular Damage
• A series of special conditions imposed upon photoreceptors puts them in what can
only be termed a high-risk, pro-oxidant environment
• Rod photoreceptor outer segments contain a high proportion of PUFAs which are
readily oxidised, while the inner segments contain a considerable number of
mitochondria, which leak a small but significant fraction of newly formed ROI
• Also, it has been shown that the partial pressure in this environment is higher than
found elsewhere in the body
11. ROI and Cellular Damage
• Under normal conditions, the production of ROI is met by an ample supply of the
detoxifying enzyme, SOD, whereas catalase and glutathione reductase are readily
available to cope with hydrogen peroxide
• These enzymes, in concert with antioxidant proteins and small molecular
reductants, form an effective antioxidant defence within the photoreceptor
• When overwhelmed, lipid peroxidation within the outer segment results
12. ROI and Cellular Damage
• Proteins make up the remaining 50% of the lipid bilayer of the rod outer segment
• Fragmentation, cross-linking and aggregation of proteins, as well as enhanced
vulnerability to proteolysis, can result from oxidation of their amino acids
• The oxidized bases of DNA, arising from interactions with ROI, are believed to
contribute significantly to ageing and age-related disorders involving many organ
systems, including the eye
13. Assessments of ROI activity
• There are various methods for assessing ROI activity; however, a consensus with
respect to which is the most valid and reliable technique is still lacking. The three
most commonly used techniques are:
(1) determination of endogenous antioxidant levels
(2) measurement of the products of oxidised macromolecules
(3) Direct detection of ROI.
14. Assessments of ROI activity
Antioxidant levels
• The concentration of antioxidants in plasma and cells, and the cellular activities of
antioxidant enzymes, can be used as a reflection of ROI activity
Products of oxidised macromolecules
• ROI damage may be identified, indirectly, by the presence of degradation products
of lipids, such as malondialdehyde, in blood and/or urine
• For assessing ROI-induced protein oxidation, protein nitrotyrosine has been widely
used as a convenient and stable marker
• Finally, urinary excretion of 8-hydroxydeoxyguanosine represents a useful means of
assessing DNA base oxidation in humans.
15. Assessments of ROI activity
Direct detection of ROI
• Direct detection of ROI can be assessed using electron spin resonance and spin-
trapping techniques
• The electron spin resonance technique is suitable for detecting ROI in vitro, but it
has limited application in vivo
• The spin-trapping technique involves the conversion of ROI to relatively inert
radicals, which are then detected by electron spin resonance analysis.
17. Endogenous Antioxidants
Glutathione
• abundant in cytoplasm, nuclei and mitochondria of cells, and is dependent on selenium as a
cofactor
• The concentration of cellular glutathione has a major effect on its antioxidant capacity, and
it varies considerably as a result of nutrient limitation, exercise and oxidative stress
• Glutathione exists in the following forms: the antioxidant reduced glutathione, known as GSH
and the oxidised form, known as glutathione disulphide (GSSG)
• The GSSG/GSH ratio in a living cell is believed to reflect oxidative stress.
19. Endogenous Antioxidants
Superoxide dismutases
• SODs are metalloproteins, some of which contain manganese, whereas others contain
copper or zinc
• SOD catalyses the quenching of the superoxide anion to produce hydrogen peroxide and
oxygen
20. Endogenous Antioxidants
Catalase
• Catalase is an iron-dependent enzyme that scavenges H2O2, either catalytically or
peroxidatively
• It has been demonstrated in human retina and RPE, where its activity has been shown to
decline with increasing age.
• Also, a reduction in retinal catalase activity has been demonstrated in eyes with AMD.
21. Exogenous Antioxidents
Vitamin A
• It is believed that vitamin A may protect photoreceptor membranes against oxidative
damage by breaking the chain reaction during lipid peroxidation
• In addition, vitamin A is also involved in the repair of cells that have been injured by
oxidation.
22. Exogenous Antioxidents
Vitamin C
• Vitamin C is a major water-soluble antioxidant
• It is an ideal scavenger because of its water solubility, stability and mobility, and because it
can be transported, reabsorbed and recycled
• Compared to plasma, all ocular tissues have very high concentrations of vitamin C.
23. Exogenous Antioxidents
Vitamin E
• Vitamin E acts synergistically with carotenoids in scavenging free radicals
• In the presence of vitamin E deficiency, various changes indicative of oxidative damage are
seen in the rod outer segments and RPE, suggesting that this vitamin protects the retina
against such injury
24. Exogenous Antioxidents
Carotenoids
• Carotenoids act as antioxidants by virtue of their free radical scavenging and singlet-oxygen
quenching capacity
• The macular carotenoids are increasingly believed to protect the macula against oxidative
damage by at least one of the following two mechanisms: filtering blue light at a
prereceptorial level, thus limiting photochemical reactions; quenching free radicals
25. Exogenous Antioxidents
Bioflavonoids
• Bioflavonoids are large polyphenolic molecules, which are derived from the peel and
coverings of teas, berries, grapes and bark
• They exhibit a myriad of properties, such as anti-inflammatory, antibacterial and antioxidant
activity.
• Of the sources of bioflavonoids, such as red wine, green tea and English blueberry, green tea
produces the most potent antioxidants known to humans
• Numerous studies have shown their unique role in protecting vitamin C from oxidation in the
body, thereby allowing the body to reap more benefits from vitamin C.
26. Oxidative Stress and AMD
• The free radical theory of ageing proposes that ageing and age-related disorders are the
result of cumulative damage resulting from reactions involving ROI
• If this theory applies to the eye, an altered antioxidant/oxidant balance should be evident for
age-related eye disease such as AMD
• The evolutionary theory of ageing proposes that there is a decline in the force of natural
selection with increasing age, and that we may have evolved with genes which promote
senescence once we have passed our period of procreation
• In other words, we do not eliminate genes that have a detrimental effect in later life if they
have a beneficial effect, or no effect, in early life.
27. Oxidative Stress and AMD
• Evidence of oxidative stress can be seen in the RPE and in the neurosensory retina with
increasing age, and this damage is most prominent in the region of the retina where early
AMD changes are seen
• It has been shown that the concentration of lipofuscin in the RPE increases with increasing
age
• Lipofuscin consists of lipid/ protein byproducts resulting from oxidatively damaged
photoreceptor outer segments
• it has been shown that lipofuscin compromises RPE cellular function
• lipofuscin generates ROI in response to irradiation with blue light, and therefore contributes
further to oxidative stress in the local environment
• RPE dysfunction contributes to the pathogenesis of ARM/AMD, and that this dysfunction is
related to lipofuscin accumulation, which, in turn, is related to oxidative injury.
28. Macular Pigment and AMD
• MP is entirely of dietary origin, and is found in high concentrations in green leafy vegetables,
fruits and egg yolk, and dietary modification can augment the optical density of MP
• MP protects the retina from photochemical (oxidative) damage directly, by acting as a free
radical scavenger, and indirectly, by filtering damaging blue light
• it has been postulated that the optical and antioxidant properties of MP confer protection
against AMD, and that the augmentation of MP through dietary modification could delay, or
even avert, the onset of AMD
• Observational studies suggest that a lack of MP is associated with several known risk factors
for AMD, including female gender, smoking, light iris colour, increasing age
29. Antioxidant and AMD
• Several large studies have examined the role of antioxidant supplementation in ARM/AMD,
the largest of which was the AREDS
• AREDS was a multicentre, prospective study of 4757 individuals aged 55–80 years, designed
to assess the effect of dietary antioxidant supplements (vitamin E, vitamin C, b-carotene and
zinc) on the clinical course of AMD
• AREDS reported a beneficial effect of supplementation with this formulation, with reduced
risk for disease progression by 25% and vision loss by 19%
30. Oxidative Stress and Cataract
• ROI can be generated in the lens as a result of exogenous (UV light) or endogenous factors
• UV light represents an important factor, since the exposure of the lens to these wavelengths
renders it vulnerable to ROI production, with consequential protein modification, lipid
peroxidation and DNA fragmentation, all of which are believed to contribute to the genesis
of cataract.
• the most important insult is protein modification, which includes protein disulphide cross-
links and high-molecular-weight aggregation
• With increasing age, the protection and repair mechanism against oxidation in the lens, the
key component of which is GSH, slowly deteriorates and becomes ineffective
• As the lens ages, de novo synthesis and the recycling system of GSH become less efficient,
resulting in a net decline in its concentration
• Protein sulfhydryl groups can undergo oxidation, thus contributing to cataract formation
31. Oxidative Stress and Glaucoma
• It is believed that raised intraocular pressure in primary open-angle glaucoma is attributable
to malfunction of the trabecular meshwork (TM) – Schlemm’s canal outflow system
• The TM is believed to be exposed to chronic oxidative stress because of the presence of ROI
in the aqueous humour, and because of the generation of ROI by mechanical stress and
intracellular metabolism
• proteasome, which protects the TM from oxidative injury by eliminating the altered proteins
damaged by ROI
• function of proteasome can be impaired by excessive exposure to oxidative stress by at least
one of the following two mechanisms:
(1) saturation of the proteasome by the presence of an excessive number of altered proteins
(2) direct oxidation of proteasome components
32. Oxidative Stress and RP
• RP is a progressive degeneration of the retina, and is best described as a phenotypic
description of several related, yet distinct, dystrophies of the photoreceptors and the pigment
epithelium
• Apoptosis represents the final common pathway of cell death in RP, and it has been
demonstrated that ROI act as mediators of retinal cell apoptosis in this condition
33. Oxidative Stress and ROP
• there is a general consensus that ischaemia–reperfusion injury, with consequential
generation of ROI during the metabolism of ATP, results in Retinopathy of Prematurity
• ATP is degraded intracellularly via adenosine monophosphate to adenosine, which is further
degraded to inosine and hypoxanthine outside the cell
• Under normal conditions, hypoxanthine is metabolised to uric acid by the enzyme xanthine
dehydrogenase (XDH), but under conditions of ischaemia or anoxia XDH is converted to
xanthine oxidase (XO)
• Metabolism of hypoxanthine by XO results in release of superoxide anions, and
consequential oxidative injury