Retinal Rhodopsin and its function in the eye, Crystalline proteins and its age-related degeneration, Kwashiorkor and xerophthalmia and other eye problems, Cornea in Kwashiorkor

1. Unit: II
Energy – Units, Metabolisms, Energy expenditure,
and Energy imbalance. Digestion, absorption and
transport of Food Proteins and eye
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2. Unit: II
Proteins and eye
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3. Retinal Rhodopsin
• Retinal rod pigments are more abundant and stable than cone pigments
• visual pigments consist of an apoprotein - opsin to which a chromophore is attached.
• The spectral properties of these visual pigments are largely determined by the retinene
chain of the chromophore
• Rhodopsin is contains the chromophore 11-cis-retinal - an aldehyde derivative of
vitamin A with λmax = 498nm
• The cone pigments consist of
▪ blue sensitive cones (λmax = 419 nm)
▪ green-sensitive cones (λmax= 531 nm)
▪ red-sensitive cones ( λmax = 558 nm)

4. Retinal Rhodopsin
• Rhodopsin is located in
the disc membranes of
the rod outer segments
(ROS) of the
photoreceptor cells of the
retina
• it comprises 80% of total
protein with the other
proteins present involved
in the phototransduction
cascade

5. RetinalRhodopsin

6. Retinal Rhodopsin
• Rhodopsin is an example of G protein coupled receptors (GPCRs)
• Rhodopsin absorbs radiations of wavelengths in or near the visible part of the
electromagnetic spectrum
• The bleaching pathway involves the isomerisation of the chromophore 11-
cisretinal around the C11==C12 double bond to form all-trans-retinal.
• The final reaction in the bleaching process involves hydrolysis and dissociation to
all-transretinaldehyde and the apoprotein opsin- a requirement for full
deactivation of light-stimulated photoreceptor cells.
• 11-cis-retinal is then regenerated and supplied to opsin by the visual cycle to
restore the dark pigment.

7. Lens Crystalline Proteins
• lens must maintain its own clarity, provide refractive power and absorb ultraviolet
(UV).
• lens is avascular and its protein concentration is the highest of any organ - 450
mg/ml
• lens proteins are uniformly packed in high density within the fibre cells
• lens is a growing tissue in which concentric layers of fibre cells continuously overlay
their predecessors.
• outer younger part of the lens is called the cortex and the older core or inner part
is called the nucleus

8. Lens Crystalline Proteins
• lens has a unique growth pattern - no protein turnover in the differentiated fibre
cells and no diffusion of proteins between cells.
• Therefore, proteins synthesized during embryogenesis are still present in fibre cells
located in the core of an aged lens
• vertebrate lens consist mainly of the structural proteins crystallins (90% of total
proteins) which are classified into α, β and ɣ
• they also contain enzymatic proteins, including glyceraldehyde-3P dehydrogenase,
glucose-6P dehydrogenase and enolase.

9. Age and denaturation
• In the nucleus of lens older proteins begin to unfold and denature with age
• Once denatured, the hydrophobic core is exposed; this tends to interact with
exposed hydrophobic regions of other denatured proteins, leading to the
formation of insoluble aggregates.
• Such insoluble protein aggregates cause light-scattering which interferes with lens
transparency and, hence, with vision (cataract).

10. UV light and Cataract
• UV radiation from sunlight is known to cause structural and functional alterations
to lens macromolecules and is one of the major risk factors in the aetiology of
human cataract formation.
• The lens fibre cells contain a group of UV filter compounds.
• These compounds absorb harmful radiation (295–400 nm), preventing it reaching
the retina, thus increasing visual acuity.
• some UV filters can over time form reactive substances which bind to the
crystallin proteins in human lens, leading to coloration, fluorescence and ultimately
cataract formation.

11. Protein Deficiency
• Kwashiorkor is a form of severe protein
malnutrition characterized by edema, and an
enlarged liver with fatty infiltrates.
• Sufficient calorie intake, but with insufficient
protein consumption, distinguishes it from
marasmus.
• Kwashiorkor cases occur in areas of famine or
poor food supply

12. Kwashiorkor: Symptoms
• The defining sign is pitting edema (swelling of the ankles and feet).
• A distended abdomen, an enlarged liver with fatty infiltrates, thinning of hair,
loss of teeth, skin depigmentation and dermatitis.
• Often develop irritability and anorexia.
• the disease can be treated by adding protein to the diet - it can have a long-term
impact on a child's physical and mental development and in severe cases may
lead to death.
• marasmus is the more frequent disease associated with malnutrition. Cachexia is
also associated

13. Xerophthalmia and Kwashiorkor
• Xerophthalmia is a medical condition in which the eye fails to produce tears. It
may be caused by vitamin A deficiency
• The conjunctiva becomes dry, thick and wrinkled. If untreated, it can lead to
corneal ulceration and ultimately to blindness as a result of corneal damage
• Xerophthalmia can be caused vitamin A deficiency
• In Kwashiorkor severe protein deficiency lead to deficiency of Retinol binding
protein (RBP) that can lead to vit A deficiency
• In such cases the patient will show vitamin A deficiency but will not respond to vit
A supplementation

14. XerophthalmiaandKwashiorkor

15. Xerophthalmia and Kwashiorkor
• Xerophthalmia is found associated with Kwashiorkor in several African and Asian
countries
• Children with concurrent severe protein deficiency should receive an additional
oral dose every two weeks until their protein status improves

16. Cornea in Kwashiorkor
• resistance of the cornea to infection is lowered in Kwashiorkor
• The Lowering of resistance of the cornea to infection must be
explained on the basis of the histopathological change brought
about by the state of malnutrition
• humoral defense reaction is impaired in Kwashiorkor
• The eye has poor inflammatory vascular response in the presence of
a severe corneal ulcer

17. Cornea in Kwashiorkor
• The normal corneal epithelium acts as a defense barrier against bacterial
infection by imperviousness of its cells.
• With the exception of gonococci, diphtheria bacilli, and viruses, the intact
corneal epithelium is impervious to bacterial toxins ordinarily present.
• But in Kwashiorkor this barrier is weakened, as the corneal epithelium is
thinned by atrophy, the cells are abnormal and may be keratinized
• Epithelial abrasions, which commonly occur in severe Kwashiorkor, may
permit the entry of bacteria, thus rendering the cornea more liable to
infection.

18. Other conditions related to Kwashiorkor
• Night blindness: Several studies indicate that night blindness is
associate with protein energy malnutrition. In a study by Hussain
et.al*, mid-upper arm circumference (MUAC) of Bangladeshi
children had a direct correlation with night blindness.
*Protein energy malnutrition, vitamin A deficiency and night blindness in Bangladeshi children. Hussain
A(1), Lindtjørn B, Kvåle G, Ann Trop Paediatr. 1996 Dec;16(4):319-25. PMID: 8985529

19. Other conditions related to Kwashiorkor
• Keratomalacia is most frequently caused by prolonged dietary deprivation of
vitamin A (i.e., primary vitamin A deficiency).
• Primary vitamin A deficiency is common in certain regions where rice is a major
component of the diet (e.g., eastern and southern Asia); rice does not contain
beta-carotene, which is converted by the body into vitamin A.
• In addition, keratomalacia is common with certain malnutrition disorders
resulting from insufficient consumption of protein and energy (i.e., protein-
calorie malnutrition, such as kwashiorkor).
• In such cases, vitamin A deficiency may result from dietary deprivation as well as
defective storage and transport of vitamin A.
• Keratomalacia occurs most commonly in developing countries due to prolonged
dietary deprivation of vitamin A or protein-calorie malnutrition.