Lipids and Eye Lokesh Ravikumar

B.OPTOM

Introduction
A lipid is any of various organic compounds that
are insoluble in water. They include fats, waxes,
oils, hormones, and certain components of
membranes and function as energy-storage
molecules and chemical messengers
The lipids are a large and diverse group of naturally occurring organic compounds that are related
by their solubility in nonpolar organic solvents (e.g. ether, chloroform, acetone & benzene) and
general insolubility in water. There is great structural variety among the lipids, as will be
demonstrated in the following sections. You may click on a topic listed below, or proceed page by
page.

2
Lipids can be classified into four main types, namely fatty acids, glycerolipids, phospholipids, and
sphingolipids

1.Fatty Acids

The common feature of these lipids is that they are all esters of moderate to long chain fatty acids.
Acid or base-catalyzed hydrolysis yields the component fatty acid, some examples of which are
given in the following table, together with the alcohol component of the lipid. These long-chain
carboxylic acids are generally referred to by their common names, which in most cases reflect their
sources. Natural fatty acids may be saturated or unsaturated, and as the following data indicate,
the saturated acids have higher melting points than unsaturated acids of corresponding size. The
double bonds in the unsaturated compounds listed on the right are all cis (or Z).

The higher melting points of the saturated fatty acids reflect the uniform rod-like shape of their
molecules. The cis-double bond(s) in the unsaturated fatty acids introduce a kink in their shape,
which makes it more difficult to pack their molecules together in a stable repeating array or
crystalline lattice. The trans-double bond isomer of oleic acid, known as elaidic acid, has a linear

3
shape and a melting point of 45 ºC (32 ºC higher than its cis isomer). The shapes of stearic and
oleic acids are displayed in the models below. You may examine models of these compounds by
clicking on the desired model picture.

Two polyunsaturated fatty acids, linoleic and linolenic, are designated “essential” because their
absence in the human diet has been associated with health problems, such as scaley skin, stunted
growth and increased dehydration. These acids are also precursors to the prostaglandins, a family
of physiologically potent lipids present in minute amounts in most body tissues.

Because of their enhanced acidity, carboxylic acids react with bases to form ionic salts, as shown
in the following equations. In the case of alkali metal hydroxides and simple amines (or ammonia)
the resulting salts have pronounced ionic character and are usually soluble in water. Heavy metals
such as silver, mercury and lead form salts having more covalent character (3rd example), and the
water solubility is reduced, especially for acids composed of four or more carbon atoms.

1. Soaps and Detergents

Carboxylic acids and salts having alkyl chains longer than eight carbons exhibit unusual behavior
in water due to the presence of both hydrophilic (CO2) and hydrophobic (alkyl) regions in the same
molecule. Such molecules are termed amphiphilic (Gk. Amphi = both) or amphipathic. Fatty acids
made up of ten or more carbon atoms are nearly insoluble in water, and because of their lower
density, float on the surface when mixed with water. Unlike paraffin or other alkanes, which tend to
puddle on the waters surface, these fatty acids spread evenly over an extended water surface,
eventually forming a monomolecular layer in which the polar carboxyl groups are hydrogen bonded
at the water interface, and the hydrocarbon chains are aligned together away from the water. This
behavior is illustrated in the diagram on the right. Substances that accumulate at water surfaces
and change the surface properties are called surfactants.

Alkali metal salts of fatty acids are more soluble in water than the acids themselves, and the
amphiphilic character of these substances also make them strong surfactants. The most common
examples of such compounds are soaps and detergents, four of which are shown below. Note that
each of these molecules has a nonpolar hydrocarbon chain, the “tail”, and a polar (often ionic)
“head group”. The use of such compounds as cleaning agents is facilitated by their surfactant
character, which lowers the surface tension of water, allowing it to penetrate and wet a variety of
materials.

4
Very small amounts of these surfactants dissolve in water to give a random dispersion of solute
molecules. However, when the concentration is increased an interesting change occurs. The
surfactant molecules reversibly assemble into polymolecular aggregates called micelles. By
gathering the hydrophobic chains together in the center of the micelle, disruption of the hydrogen
bonded structure of liquid water is minimized, and the polar head groups extend into the
surrounding water where they participate in hydrogen bonding. These micelles are often spherical
in shape, but may also assume cylindrical and branched forms, as illustrated on the right. Here the
polar head group is designated by a blue circle, and the nonpolar tail is a zig-zag black line.

An animated display of micelle formation is presented below. Notice the brownish material in the
center of the three-dimensional drawing on the left. This illustrates a second important factor
contributing to the use of these amphiphiles as cleaning agents. Micelles are able to encapsulate
nonpolar substances such as grease within their hydrophobic center, and thus solubilize it so it is
removed with the wash water. Since the micelles of anionic amphiphiles have a negatively charged
surface, they repel one another and the nonpolar dirt is effectively emulsified. To summarize, the
presence of a soap or a detergent in water facilitates the wetting of all parts of the object to be
cleaned, and removes water-insoluble dirt by incorporation in micelles

2. Fats and Oils

The triesters of fatty acids with glycerol (1,2,3-trihydroxypropane) compose the class of lipids
known as fats and oils. These triglycerides (or triacylglycerols) are found in both plants and
animals, and compose one of the major food groups of our diet. Triglycerides that are solid or
semisolid at room temperature are classified as fats, and occur predominantly in animals. Those
triglycerides that are liquid are called oils and originate chiefly in plants, although triglycerides from
fish are also largely oils. Some examples of the composition of triglycerides from various sources
are given in the following table.

As might be expected from the properties of the fatty acids, fats have a predominance of saturated
fatty acids, and oils are composed largely of unsaturated acids. Thus, the melting points of
triglycerides reflect their composition, as shown by the following examples. Natural mixed
triglycerides have somewhat lower melting points, the melting point of lard being near 30 º C,
whereas olive oil melts near -6 º C. Since fats are valued over oils by some Northern European
and North American populations, vegetable oils are extensively converted to solid triglycerides

5
(e.g. Crisco) by partial hydrogenation of their unsaturated components. Some of the remaining
double bonds are isomerized (to trans) in this operation. These saturated and trans-fatty acid
glycerides in the diet have been linked to long-term health issues such as atherosclerosis.

Triglycerides having three identical acyl chains, such as tristearin and triolein (above), are called
“simple”, while those composed of different acyl chains are called “mixed”. If the acyl chains at the
end hydroxyl groups (1 & 3) of glycerol are different, the center carbon becomes a chiral center
and enantiomeric configurations must be recognized.

3. Waxes

Waxes are esters of fatty acids with long chain monohydric alcohols (one hydroxyl group). Natural
waxes are often mixtures of such esters, and may also contain hydrocarbons. The formulas for
three well known waxes are given below, with the carboxylic acid moiety colored red and the
alcohol colored blue.

Waxes are widely distributed in nature. The leaves and fruits of many plants have waxy coatings,
which may protect them from dehydration and small predators. The feathers of birds and the fur of
some animals have similar coatings which serve as a water repellent. Carnuba wax is valued for its
toughness and water resistance.

4. Phospholipids

Phospholipids are the main constituents of cell membranes. They resemble the triglycerides in
being ester or amide derivatives of glycerol or sphingosine with fatty acids and phosphoric acid.
The phosphate moiety of the resulting phosphatidic acid is further esterified with ethanolamine,
choline or serine in the phospholipid itself. The following diagram shows the structures of some of
these components. Clicking on the diagram will change it to display structures for two
representative phospholipids. Note that the fatty acid components (R & R’) may be saturated or
unsaturated.

Prostaglandins Thromboxanes & Leukotrienes

The members of this group of structurally related natural hormones have an extraordinary range of
biological effects. They can lower gastric secretions, stimulate uterine contractions, lower blood

6
pressure, influence blood clotting and induce asthma-like allergic responses. Because their
genesis in body tissues is tied to the metabolism of the essential fatty acid arachadonic acid
(5,8,11,14-eicosatetraenoic acid) they are classified as eicosanoids. Many properties of the
common drug aspirin result from its effect on the cascade of reactions associated with these
hormones.

The metabolic pathways by which arachidonic acid is converted to the various eicosanoids are
complex and will not be discussed here. A rough outline of some of the transformations that take
place is provided below. It is helpful to view arachadonic acid in the coiled conformation shown in
the shaded box.

Lipds and eye

7
The major lipid of the human lens is
dihydrosphingomyelin

Introduction….

• Lipids are key components of the retina, and

are closely

Associated with the aging processes.

• Omega-3 fatty acids show protective

properties against

8
Inflammation and neurodegeneration in
retinal aging and

The development of AMD

• The eye retina is a part of the central

nervous system,

Together with the brain and the spinal cord

and as such is

Also naturally rich in lipids

Lipids as crucial components of the retina

9
• The retina covers the internal side of the
posterior chamber of the eye

• The retina is composed of

• neurosensory tissue: neuroretina,

• a pigment epithelium: retinal pigment

epithelium (RPE)

• The main function of the neuroretina is to

convert the light stimulus into an electrical

Signal that can be decoded by the brain

10
• The RPE creates a physical and metabolic
barrier between the neuroretina and the

Choriocapillaris that limits the entry of

exogenous compounds in the neuroretina.

• One of the primary function of the RPE is to

eliminate the metabolic debris generated by

Photoreceptors.

• The RPE exhibits an endogenous capacity

to synthesize and secrete lipoprotein-like

Particles

11
• Low density lipoprotein particles (LDL)
participate significantly in retinal lipid supply

Lipids as crucial components of the retina

• Lipids account for about 25% of the dry

matter in the neuroretina.

• Phospholipids are the prominent lipids

therein (more than 85%), while

Cholesterol is present as free cholesterol

(10%), and to a lesser extent as

12
Cholesteryl esters (less than 2%)

• Phospholipids are present in great quantity

in the outer segment of rods and

Cones.

• Docosahexaenoic acid (DHA) is the main

long-chain polyunsaturated fatty acid in

The phospholipids of the neuroretina: 12–

20% of the fatty acids in human and

More than 30% in rodent

13
• DHA is involved in the phototransduction
pathway by enhancing the ability of the

Photopigment rhodopsin to undergo the

transition to the active form.

• Modifying the dietary intake of omega-3 fatty

acids may have consequences on

The level of DHA in the retina and possibly its

functioning

Lipids as crucial components

of the retina

14
• The potential of a diet enriched in DHA and
EPA (eicosapentaenoic acid)

To increase the level of the longer chain

omega-3 fatty acids (EPA; DPA,

Docosapentaenoic acid; and DHA) in the

retina has clearly been

Demonstrated

• Intervention trials have been conducted in

pregnant and lactating

15
Women and premature and at-term babies in
order to evaluate the

Efficacy of dietary long chain omega-3 fatty

acids to improve vision

Performance in infants.

• The positive effect of omega-3 fatty acids

was obvious only in studies

Where the intake of DHA was higher than 1g

daily

Aging of the retina

16
• Aging, and to a larger extent AMD, is
associated with the accumulation of

Extracellular lipid particles at the basement of

the RPE, within Bruch’s membrane

• These lipid particles are called drusen

(singular, “druse”).

• Drusen comprise multiple components

including lipofuscin, fibrillar and nonfibrillar
amyloid, cholesterol, glycoproteins,
vitronectin, inhibitors and activators of

17
The extracellular matrix, complement factor
H, complement component C3, and

Zinc.

• Morphologic criteria are used to define

drusen as soft or hard: soft drusen appear

Often liquefied or oily, whereas hard drusen

are partially or completely crystallized.

• Hard drusen are the most abundant type

throughout the retina.

18
• Soft drusen appear specifically in the
macula and are considered as the most

Fateful of age-related macular lesions.

Aging of the retina & Lipids

• The “lipid wall”, made of cholesterol,

participates in the age

Associated thickening of Bruch’s membrane

that increases hydraulic

19
Resistance and may reduce the fluxes of
nutrients to the retina

• AMD targets a specific area of the retina: the

macula.

• High fat intake has been associated with

higher risk for AMD.

• Smoking and light exposure are, for

instance, recognized as

Promoting factors

20
Lipids are powerful factors
preventing retinal

Stress, aging and death

• Glaucoma is characterized by the death of

ganglion cells that, in the last stages

Of the pathology, induces blindness.

• Various factors are associated with

glaucoma, including elevated intra-ocular

21
Pressure

• A reduced activation of glial cells in the

group of rats fed both omega-3 and

Omega-6 fatty acids was observed,

suggesting their potential to prevent retinal

Stress.

• In a study it was observed that participants

who have the highest omega-3

Long-chain polyunsaturated fatty acid (EPA

and DHA) intake (0.11% of total

22
Energy intake) were 30% less likely to
develop Geographic atrophy and

Neovascular AMD than low consumers (0.01%

of total energy intake)

Lipids in tears

• Tear film is actually composed of three

basic layers: mucin, water and

23
Lipids from posterior to anterior.

• Lipid or oily layer is the outermost layer of

tear film formed at airtear interface from the
secretions of Meibomian, Zeis, and Moll

Glands.

• This layer prevents the overflow of tears,

retards their evaporation

And lubricates the eyelids as they slide over

the surface of the globe.

24
• Lipids within tears help prevent water
evaporation from the ocular

Surface and protect the eye against infection

• Prolonged dry eyes leads to cloudy cornea,

inhibiting self repair of the

Damaged cornea

Eye Diseases linked to lipids

25
• Arcus senilis refers to an annular lipid
infiltration of corneal

Periphery. This is an age-related change

occurring bilaterally in 60

Percent of patients between 40 and 60 years

of age and in nearly all

Patients over the age of 80.

• Fatty degeneration (Lipoid keratopathy)of

cornea is characterised by

26
Whitish or yellowish deposits. The fat
deposits mostly consist of

Cholesterol and fatty acids

• Diabetic retinopathy: hyperlipidemia is a

risk factor

• Seborrhoeic or squamous blepharitis:

glands of Zeis secrete

Abnormal excessive neutral lipids which are

split by Corynebacterium

Acne into irritating free fatty acids

27
Eye Diseases linked to lipids

• Xanthelasma:

• These are creamy-yellow plaque-like lesions

which frequently involve

The skin of upper and lower lids near the

inner canthus.

• Xanthelasma represents lipid deposits in

histiocytes in the dermis of

28
The lid.

• These may be associated with diabetes

mellitus or high cholesterol

Levels.

Eye Diseases linked to lipids

• THE DRY EYE:

• Lipid deficiency is extremely rare.

29
• It has only been described in some cases of
congenital anhidrotic

Ectodermal dysplasia along with absence of

meibomian glands.

• However, lipid abnormalities are quite

common in patients with chronic

Blepharitis and chronic meibomitis

• Lipid soluble drugs have better permeability

in eyes

30
• Asteroid hyalosis.

• It is characterised by small, white rounded

bodies suspended in the vitreous gel.

• These are formed due to accumulation of

calcium containing lipids.

• Asteroid hyalosis is a unilateral,

asymptomatic condition usually seen in old
patients

With healthy vitreous.

31
• There is a genetic relationship between this
condition, diabetes and

Hypercholesterolaemia.

• The genesis is unknown and there is no

effective treatment

Eye Diseases linked to lipids

Lipodermoids.

• These are solid tumours usually seen

beneath the conjunctiva.

32
• These are mostly located adjacent to the
superior temporal quadrant of

The globe.

• These do not require any surgical

intervention unless they enlarge

Significantly

33
Eye health

• The role of omega-3 fatty acids in the

prevention of neuroretinal cell

Death has been increasingly appreciated over

the last few years.

• It has been demonstrated that they help

resolve inflammation and

Neurodegeneration in response to
extracellular stresses, including
34
Oxidative stress

• Epidemiological studies consistently

support the benefit of

Consumption of not only fish and marine

products rich in omega-3

Fatty acids, but also of fruits and vegetables

that are rich in

Carotenoids.

35
• These dietary recommendations should be
considered by clinicians

Providing care to patients at early stages of

AMD in order to prevent the evolution into the
late stages

36