JAYS QUIZPAD: Vision, Vitamin A Deficiency and Xerophthalmia

Biochemistry of Vision

• Vitamins are potent organic compounds needed in small amounts for optimal growth and health.
• Vitamins aren't used for energy; they help utilize other nutrients like carbs, proteins, and fats.
• Most vitamins are not made in the body; they must be obtained through diet.
• Many vitamins act as co-enzymes.

Classification of Vitamins

• Vitamins are classified into two main groups:
  • Fat-soluble vitamins: Vitamin A, D, E, and K
  • Water-soluble vitamins: Vitamin C and the B-complex vitamins. The B-complex vitamins include subgroups for energy-releasing (B1, B2, B3, B6, B7, and pantothenic acid) and hematopoietic (folic acid and B12) functions.

Vitamin A

• Vitamin A is a broad term for similar chemical compounds.
• It is the first recognized fat-soluble vitamin.
• Two main forms of vitamin A:
  • Preformed vitamin A: Retinoids (found in animal products). Four forms of retinoids are retinol, retinal, retinoic acid, and retinyl esters.
  • Provitamin A: Carotenoids (found in plants). Beta-carotene is the most important.

Preformed Vitamin A: Retinoids

• Active (usable) form of vitamin A.
• Four categories of retinoids:
  • Retinol
  • Retinal
  • Retinoic acid
  • Retinyl esters
• All retinoids are absorbed by the body as retinol.
• Sources: animal products like liver, fish, fish oils, milk, eggs. Liver is the richest source.

Structure of Vitamin A

• Unsaturated organic compounds.
• All forms of Vitamin A have a beta-ionone ring with an attached isoprenoid chain, called a retinyl group.

Retinol

• Vitamin A alcohol.
• Pure alcohol form is unstable.
• Present in animal tissues as a retinyl ester with a long chain fatty acid.

Retinal

• Vitamin A aldehyde.
• Obtained by oxidizing retinol.
• Previously known as retinene.
• Retinal and retinol are interconvertible (can change from one form to the other).

Retinoic Acid

• Vitamin A acid.
• Product of oxidizing retinal.
• Cannot be converted back to retinal or retinol.

Provitamin A: Carotenoids

• Precursors of vitamin A.
• Predominantly beta-carotene.
• The body must convert them into active vitamin A after consumption.
• Sources: plant products like carrots, leafy greens, papaya, mango, and brinjal.

Types of Carotenoids

• Alpha-carotene yields 1 molecule of vitamin A.
• Beta-carotene yields 2 molecules of vitamin A.
• Gamma-carotene yields 1 molecule of vitamin A.

Vitamin A Sources

• Vitamin A comes from animal sources (eggs, meat, and dairy products).
• Beta-carotene, a precursor to vitamin A, comes from green, leafy vegetables and intensely colored fruits and vegetables.

Biochemical Functions of Vitamin A

• Essential for vision in dim light.
• Necessary for maintaining normal epithelium. Goblet cells synthesize mucus to help with antimicrobial defense.
• Required for embryonic development (e.g. lungs, heart, eyes, and ears). Regulates expression of growth hormone gene.
• Acts as an antioxidant. Carotenoids neutralize free radicals, potentially preventing cancer and other diseases.
• Crucial for immune function – ensures proper functioning of mucosal cells, membranes, and epithelial layers (body's first line of defense). Helps lymphocytes and white blood cell development.
• Crucial for eye health (formation of rhodopsin for night vision and maintenance of healthy cornea and conjunctiva).

Role of Vitamin A in the Eye

• Crucial for forming rhodopsin (used in night vision).
• Maintains healthy cornea and conjunctival cells.

Sections for Detailed Study of Vitamin A

• Vitamin A Absorption and Storage
• Transport from Liver to Eye
• Synthesis of Visual Pigments
• Light-Induced Changes in Visual Pigments

Vitamin A Absorption and Storage

• Dietary vitamin A (carotenoids and retinol) is absorbed.
• In the intestines, vitamin A is re-esterified.
• Enters bloodstream via intestinal lymphatics.
• Most retinol goes to the liver (90% stored).
• In liver, retinol binds to retinol-binding protein (RBP), creating a stable form.

Transport from Liver to Eye

• Retinol-protein complex enters bloodstream.
• Binds to specific receptors on basal surfaces of retinal pigment epithelial (RPE) cells.
• Only retinol enters the RPE cells; RBP stays outside.

Synthesis of Visual Pigments

• Retinol remains unchanged in RPE cells.
• Retinol enters photoreceptor outer segments.
• Retinol oxidizes into retinene (11-cis retinal).
• Retinene combines with opsin to form rhodopsin.
• NAD oxidative system in RPE supports rhodopsin formation.

Light-Induced Changes in Visual Pigments

• Light falls on the retina, absorbed by photoreceptors.
• Photochemical changes in outer segments initiate electrical changes.
• Light-induced changes in rods involve the following:
  • Rhodopsin bleaching
  • Rhodopsin regeneration
  • Visual cycle

Rhodopsin Bleaching and Regeneration

• Rhodopsin is a combination of opsin (protein) and retinene (vitamin A aldehyde).
• Light absorption changes 11-cis retinal to all-trans retinal in rhodopsin.
• This separation (photodecomposition) bleaches rhodopsin.
• Rhodopsin regeneration involves:
  • All-trans retinal entering the chromophore pool in photoreceptors and RPE cells.
  • Conversion of all-trans retinal to 11-cis retinal by the enzyme retinal isomerase.
  • 11-cis retinal rejoining opsin to reform rhodopsin.

Visual Cycle

• Constant light stimulation: Photoreceptor bleaching = photoreceptor regeneration.
• Equilibrium between photodecomposition and regeneration of visual pigments forms the visual cycle.

Phototransduction

• Process of converting light energy to electrical signals.
• Occurs in photoreceptors.

Photoreceptor Membrane Potential

• Photoreceptors (rods and cones) are slightly depolarized relative to a typical neuron.
• Instead of a -70mV resting potential, photoreceptors have a -50mV potential.

In Dark

• Inner segment of photoreceptors pump Na+ out.
• Negative potential inside entire cell.
• Na+ channels in photoreceptor outer segments are open due to cGMP.
• Na+ from extracellular fluid flows into the outer segment, producing a dark current that creates a slight depolarization.

In Light

• Light striking photoreceptors reduces cGMP.
• Some Na+ channels close.
• Results in photoreceptor hyperpolarization.
• Increased negativity of membrane potential rather than decreased negativity (depolarization).

Under Dark Conditions

• Photoreceptors are depolarized.
• Continuously release neurotransmitter glutamate.

Under Light Stimulation

• Photoreceptors are hyperpolarized.
• Reduction in glutamate release.

Limited Sodium Channels

• Number of sodium channels in rod outer segments limits the magnitude of rod hyperpolarization.
• Only about 10 percent of a rod's rhodopsin bleaching affects a critical number of Na+ channels needed to prevent further hyperpolarization.

Activation Cascade

• Incident light causes retinene transformation to the all-trans form.
• Opsin configuration changes.
• Transducin (G protein) is activated.
• Alpha subunit separates from transducin (Ga).
• Ga activates cGMP PDE.
• cGMP converts to 5'-GMP.
• Closure of leaky Na+ channels
• Hyperpolarization to -70mV
• "Switching off"

Decrease in Intracellular Ca2+, Decrease Glutamate Release, and Neural Pathways

• Light decreases intracellular Ca2+.
• Decreases glutamate release by photoreceptors.
• Neural pathways transmit the electrical signal.

Vitamin A Deficiency

• Causes include dietary deficiency, poor intestinal absorption, insufficient vitamin A stored in the liver, and other diseases.
• Conditions like night blindness (early symptom) and xerophthalmia (general term for impaired vitamin A metabolism) may arise. Xerophthalmia can extend to cornea destruction.

Xerophthalmia

• General term for eye manifestations resulting from impaired vitamin A metabolism, from night blindness to corneal destruction.
• Xeros - dry; ophthalmia - eye.
• Typically synonymous with vitamin A deficiency.

Prevalence of Vitamin A Deficiency

• Leading preventable cause of childhood blindness worldwide.
• Estimated that 30% of the world's blindness is related to vitamin A deficiency.

Night Blindness

• Earliest symptom of vitamin A deficiency.
• Difficulty seeing in dusky or dark environments.

Prevention of Vitamin A Deficiency

• Breastfeeding.
• Vitamin A supplementation.
• Food fortification.
• Promoting vitamin A-rich diets.

Test your knowledge on vitamin A deficiency and related terms with this quiz. Explore symptoms like xerophthalmia and the importance of vitamin A in overall health. This quiz covers essential concepts about vitamin A and its prevention.