ROLE OF OMEGA 3 FAATY ACIDS IN DIABETIC RETINOPATHY

1. Role of Omega 3 Fatty Acids in Diabetic Retinopathy
•Efficacy or Marketing
Dr. Preetiilal
M.B.B.S., M.S.(Ophtho), Fellow LVPEI
Dr. Nandlal Hospital, Ajmer

2. Disclaimer
No financial interest of the author
lies behind the presentation

3. Diabetic Retinopathy
• Retinopathy is one of the most severe ocular complications of diabetes
and is a leading cause of acquired blindness in young adults.
• The cellular components of the retina are highly coordinated but very
susceptible to the hyperglycemic environment.
• The metabolic abnormalities of diabetes cause mitochondrial superoxide
overproduction(ROS) in endothelial cells of small retinal vessels.
• This oxidative stress plays a pivotal role in the development of
microvascular diabetic complications.
 Microvascular leakage
 Microvascular blockage

4. Pathogenesis of Diabetic Retinopathy
• This increased superoxide production causes the activation of five major
pathways involved in the pathogenesis of complications:
 polyol pathway flux,
 increased formation of advanced glycation end-products (AGEs),
 increased expression of the receptor for AGEs and its activating ligands,
 activation of protein kinase C (PKC) isoforms, and
overactivity of the hexosamine pathway.
Increased intracellular ROS cause
• defective angiogenesis in response to ischemia
• activate a number of pro-inflammatory pathways

5. Pathogenesis of Diabetic Retinopathy
• Microangiopathy – Microvascular complications which have been
directly linked to glycaemic control
• Consists of
1. loss of intramural pericytes
2. Basement membrane thickening
3. Increase plasma viscosity
4. Increase platelet aggregation
5. Progressive closure of retinal capillaries
Which ultimately lead to:

6. Vascular abnormalities
• Loss of pericytes and BM thickening weak endothelium
• Dilatation of vessels microaneurysms
• Breakdown of blood retinal barrier(BRB) leakage of vascular
contents
Oedema Haemorrhage
• Aggregation of platelets capillary non perfusion retinal ischaemia
opening up shunt vessels re-establish blood supply
(IRMA)
(neovascularisation) release VEGF

7. Vascular abnormalities
• Loss of pericytes and BM thickening weak endothelium
• Dilatation of vessels microaneurysms
• Breakdown of blood retinal barrier(BRB) leakage of vascular
contents
Oedema Haemorrhage
• Aggregation of platelets capillary non perfusion retinal ischaemia
opening up shunt vessels re-establish blood supply
(IRMA)
(neovascularisation) release VEGF

8. Management of Diabetic Retinopathy
• Control of Diabetes
• Laser Photocoagulation - Focal
- Grid
- Panretinal
• Intravitreal steroids
• Intravitreal anti-VEGF - monotherapy or adjuvant
• Intravitreal surgery

9. Link between DR and Omega 3 fatty acids
• Researches show a link between Omega 3 Fatty Acids and
prevention and treatment of diabetic retinopathy.
• Omega 3 fatty acids depresses activation and expression of
vascular endothelial growth factor (VEGF)-specific tyrosine
kinase receptor
• Also, Inhibits proinflammatory enzyme Cyclooxygenase 2
• The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina.
SanGiovanni JP1, Chew EY. Prog Retin Eye Res. 2005 Jan;24(1):87-138.

11. Characteristics of Omega 3 fatty acids:
• A double bond at the 3rd carbon from omega (ω) end of this long chain
fatty acid(n=22).
• Essential fatty acids as these cannot be produced in the body and can
only be obtained from diet.
• Important part of the cell membranes of the body especially neurons
present in the nervous system and retina.
• Three in number - Alpha Linolenic Acid (ALA)
-Eicosapentanoic Acid(EPA)
- Decosahexanoic Acid (DHA)

13. N6:N3 Balance
• The eicosanoids made from omega-6s are generally more potent
mediators of inflammation, vasoconstriction, and platelet aggregation
than those made from omega-3s.
• Because both classes of fatty acids compete for the same desaturation
enzymes, ALA is a competitive inhibitor of linoleic acid metabolism.
• Similarly, EPA and DHA can compete with arachidonic acid for the
synthesis of eicosanoids(prostaglandins).
• Thus, higher concentrations of EPA and DHA than arachidonic acid tip the
eicosanoid balance toward less inflammatory activity.

14. Role of Omega 3 fatty acids in eye
• Reduce the release of prostaglandins 2, TxA2 - anti-inflammatory
• Sensitise insulin receptors – decrease insulin resistance
• Increase the release of Thrombolytic agents like Thromboxane A3, and
Prostaglandin 3
Thus ,
Stabilises the capillary endothelium and BRB
Decrease the viscosity of blood reduce thrombus formation
Maintains capillary perfusion
Reduce new vessel formation

15. Dietary Sources of Omega 3 fatty acids
•Cold water fish and shellfish - salmon,
sardines, mackerel, herring, and tuna.
• Fish is contaminated with deadly poisons like mercury,
polychlorinated biphenyls (PCBs), dioxins, and pesticide residues.
• Very high levels of mercury can damage nerves in adults and disrupt
development of the brain .
• DHA and EPA are present in fish but they are originally synthesized by
microalgae, not by the fish. When fish consume phytoplankton that
consumed microalgae, they accumulate the omega-3s in their tissues(*).
*Harris WS. Omega-3 fatty acids. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed.
London and New York: Informa Healthcare; 2010:577-86.

16. Plant sources
• Flax seeds and walnuts
• Plant foods typically only contain alpha-linolenic acid (ALA).
• ALA is not as active in the body and must be converted to two other
forms of omega-3 fatty acids — eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) — to bestow the same health benefits.
• Unfortunately, our body’s ability to convert ALA is limited. Only about 5%
of ALA is converted to EPA, while less than 0.5% is converted to DHA.
• Thus, if we don’t supplement with fish oil or get EPA or DHA from our
diet, it’s important to eat a good amount of ALA-rich foods to meet your
omega-3 needs.

17. Adequate intake: of Omega 3s in grams
• Established by National Academy of Medicine(US)
Age Male Female
Birth – 6 months 0.5 0.5
6-12 months 0.5 0.5
1-3 years 0.7 0.7
4-8 years 0.9 0.9
9-13 years 1.2 1.0
14-18 years 1.6 1.1
19-50 years 1.6 1.1

18. ALA, DHA and EPA in food
• Established by U. S. Department Of Agriculture(USDA)
Food ALA DHA EPA
Flax seed 7.26
Salmon 1.24 0.59
Walnuts 0.76
Soybean oil, 1 tbsp 0.92
Mayonnaise, 1tbsp 0.74
Refried beans 0.21
Tuna, 3 ounce 0.17 0.02
Kidney beans, ½ cup 0.10
Baked beans, canned 0.07
Whole wheat bread, 1 slice 0.04
Egg, 1 egg 0.03
Chicken breast, 3 ounce 0.02 0.01
Low fat milk 1%, I cup 0.01

19. Doses and recommendations
• Average daily Indian diet provides 0.5 – 1.0 gms of omega 3 fatty acids.
• Dietary supplement for normal healthy adult – 250 – 500mg/ day
•Therapeutic doses of Omega 3 fatty acids
1-2 gms/ day

20. Road to health, ultra wellness and longevity
• For centuries ratio of Omega-6 and Omega-3 was perfect
e.g. 2:1 or even 4:1 (very ideal ratio).
• But after the global switch to industrial agriculture and processed foods it
is 20:1 or more (!!!).
• This throws the body into the state of chronic inflammation, giving rise to
a whole array of clot- and inflammation-related chronic diseases.
• Dietary sources of omega-6 fatty acids include:
 Poultry, eggs, nuts, sesame seeds, cereals
 whole grain breads, pumpkin seeds, most vegetable oils
 Flax or linseed oil, soybean oil, corn oil, palm oil
 Cottonseed oil, sunflower oil, safflower oil.

21. Overdose of Omega 3 fatty acids
• Taking up to 4gm/day is usually safe (though not required).
• But higher doses may cause ill effects.
• Interact with anti coagulants
 Side effects - low Blood pressure,
- bleeding,
- stroke,
- hypervitaminoses,
- insomnia,
- diarrhoea,
- acid reflux.

22. ARE THE PATIENTS TAKING THE RIGHT DOSE
DOSE OF EFFICACY DOSE OF MARKETING
≠ DOSE OF AFFORDABILITY

23. Formulations available in the Indian market
• All anti oxidants are not omega 3 fatty acids
• These are very expensive
• Available in different preparation:
Omega 3 fatty
acids (in mg)
ALA EPA DHA
150 90 60
300 180 120
500 325 175

24. Formulations available in the Indian market

25. Thankyou