MODULE 6: lens physiology

Purpose of the lens

Focus light on the retina for clear vision.

Two properties for clear vision

Transparency and gradient of refractive index (GRI).

Five keys to lens transparency

Absence of blood vessels, Few cellular organelles, Orderly arranged fibers, Barrier to extracellular diffusion, Matching refractive index of membranes and cytoplasm

Minimal light scatter

Transparency.

Why is the lens avascular?

To prevent light scatter; fetal vessels regress by 2nd trimester.

Persistent fetal vasculature

What happens if fetal vasculature persists?

Why do lens fibers lose organelles?

To reduce light scatter along the visual axis.

Stabilization of fiber cell alignment

Ball-and-socket joints (periphery) and tongue-and-groove interdigitations (nucleus).

Role of the diffusion barrier

Limits solutes but allows nutrients and antioxidants in.

Importance of matching refractive index

Reduces light scatter between irregular fiber cells in the nucleus.

Gradient of Refractive Index (GRI)

Determined by the water-to-protein (crystallin) ratio.

GRI creates ___ spherical abberration

negative

Where is the refractive index highest?

In the nucleus (lower in periphery).

the cornea makes up __ of the refractive power of the eye

2/3

the lens makes up __ of the refractive power of the eye

1/3

Importance of GRI optically

It corrects spherical aberration for a sharper image.

Why is lens metabolism specialized?

Because internal fibers lack mitochondria and oxygen.

Key metabolic features of the lens

Low O₂ levels, High ATP reserves, Maintains pH, ion, and water balance, Prevents protein oxidation.

How does the lens get energy?

From glucose in aqueous and vitreous humor via facilitated transport.

Anaerobic Glycolysis occurs in

fiber cells of the inner cortex and nucleus

amount of glucose used in anaerobic respiration

70-80%

amount of E produced by anaerobic respiration

70-90%

Key enzymes in Anaerobic Glycolysis

Hexokinase, phosphofructokinase, pyruvate kinase.

Rate-limiting enzyme in Anaerobic Glycolysis

Hexokinase.

Aerobic Respiration (Krebs) occurs in

lens epithelial and outer cortical fiber cells

amount of glucose used by aerobic respiration

3%

amount of E produced by aerobic respiration

20%

Efficiency of Aerobic Respiration compared to glycolysis

Produces ~36 ATP per glucose.

importance of Hexose Monophosphate Shunt (HMP)

Produces NADPH, which protects against stress (regenerates GSH) and is used in the sorbitol pathway

Hexose monophosphate shunt occurs in

lens epithelial and outer cortical fiber cells

amount of glucose used by hexose monophosphate shunt

14%

Aerobic Respiration

Occurs in lens epithelial and outer cortical fiber cells.

Efficiency of Aerobic Respiration

Produces ~36 ATP per glucose.

Importance of NADPH

Regenerates glutathione (GSH) and protects from oxidative stress.

Sorbitol Pathway

Glucose enters when hexokinase is saturated (high glucose).

sorbitol pathway occurs in

epithelial cells, cortex

does the sorbitol pathway produce energy?

no

Cataract Formation from Sorbitol

Sorbitol accumulates → draws in water → fiber swelling → opacity.

Enzymes in the Sorbitol Pathway

Aldose reductase and sorbitol dehydrogenase.

Oxidative Stress

Imbalance between free radicals and antioxidants.

Sources of Free Radicals

Pollution, smoking, UV light, chemicals, poor diet, X-rays.

Key Antioxidants in the Lens

GSH, catalase, peroxidase, superoxide dismutase, and vitamin C.

Glutathione (GSH)

Synthesized in lens epithelium, key antioxidant

Function of GSH

Prevents crystallin aggregation, light scatter, and protein crosslinking.

Regeneration of GSH

The hexose monophosphate shunt.

UV Absorption in the Lens

The lens absorbs UVA (cornea absorbs UVB).

lens absorbs

UVA

cornea absorbs

UVB

Tryptophan Metabolites Build-up

Causes yellowing of the lens.

Cause of Nuclear Cataract

Chronic oxidative stress.

Importance of Electrolyte Balance

Delivers nutrients/removes waste, maintains negative membrane potential, preserves gradient refractive index.

Resting Potential of the Lens

-70 mV (inside negative).

Ion Permeability in Lens Membrane

More permeable to Potassium (K⁺).

Factors Altering Membrane Permeability

Aging and diabetes.

Na⁺/K⁺ ATPase Pump

Pumps 3 Na⁺ out, 2 K⁺ in; maintains ionic gradient and provides energy for other transporters.

Location of Na⁺/K⁺ Pumps

Lens epithelium and peripheral fiber cells.

Effect of Na⁺ Diffusion Inward

Brings glucose and amino acids via co-transport.

Amino Acid Transport in Lens

Co-transport from aqueous humor using Na⁺ gradient.

Importance of Low Ca²⁺ in Lens

High Ca²⁺ activates calpain → crystallin breakdown → opacity.

Maintenance of Low Ca²⁺ Levels

Ca²⁺/ATPase pumps.

Normal Water Content of Adult Lens

~65% (lower in nucleus).

Effect of Higher Water Content

Disrupts tight packing → light scatter.

Mechanism to Keep Water Out of Lens

Active ion transport balancing Na⁺, K⁺, and Cl⁻ gradients.

Importance of Metabolism, Ion, and Water Balance

Disruption → oxidative damage, swelling, and cataract formation.

there is high __ in the lens

K+

there is low __ in the lens

Na+, Ca2+, O2, H2O