Anatomy and Physiology of

Aqueous Humor

Sumit Singh Maharjan

Anatomy

Angle of anterior chamber

Angle of the Anterior chamber

Gonioscopic grading of Angle

Aqueous Outflow system

Trabecular meshwork

Functions of Aqueous Humor

• Maintenance of Intraocular pressure• Metabolic role cornea lens vitreous and retina• Optical function• Clearing function

Physicochemical properties

• volume: 0.31ml (0.25ml in Ant. Chamber and 0.06 in post chamber)

• Refractive index: 1.336• Density: slightly greater than water, its viscocity is

1.025-1.040• Osmotic pressure: slightly hyperosmotic to plasma by

3-5mosm/l• PH: 7.2• Rate of formation: 2-2.5microliter/min

Biochemical composition

• Water: 99.9%• Proteins: 5-16mg/100ml• Amino acids: aqueous/plasma concentration varies from

0.08-3.14• Non colloidal constituents: conc. of ascorbate, pyruvate,

lactate in higher amount while urea and glucose are much less.

• Inulin and steroid• Prostaglandins• Cyclic AMP

Composition of Aq. humor of the ant. and post. chamber

• Differs because of the constant metabolic interchange during intraocular course

• Diffusional exchange across the iris is a significant factor, since iris vessels are permeable to anions and non-electrolytes

• Some striking differences are: Bicarbonate in post. chamber is higher because freshly

secreted fluid has a much higher concentration and due to diffusion into the vitreous and into the blood from iris and decomposition by the acids formed by the lens and cornea metabolism, its level decreases in ant aqueous

Chloride concentration in newly formed aqueous is lower because diffusion of chloride from the blood raises the choride level in ant chamber

Ascorbate concentration in post is higher because diffusion occurs of ascorbic from the ant chamber to blood

Factors affecting composition of the Aqueous Humor

1. Blood-ocular barrier• posterior blood-retinal barrier• Anterior blood-aqueous barrier2. Hemodynamic factors influencing stromal pool3. Diffusional exchange across the iris4. Metabolic process5. Rate of aqueous drainage6. The quality of aqueous

Blood-retinal barrier

Blood-aqueous barrier

Clinical application of blood ocular barrier

• Hyperosmotic agents• Ocular penetration of systemically administered

antibiotics

Formation of aqueous humor

• Ciliary processes are the site of aqueous production• Aqueous humor primarily derived from plasma

within the capillary network of ciliary processes• Presently it is agreed that diffusion, ultrafiltration,

and secretion play role in aqueous production at different levels

• Major factor in aqueous production is active secretion (70%), ultrafiltration accounts for 20% and osmosis 10%.

Diffusion

In the process of aqueous production, the lipid soluble substance are transported by diffusion through the lipid portions of the cell membrane of the ciliary processes, proportional to a concentration gradient across the membrane.

Ultrafiltration

Secretion

• Secretion implies an active process that selectively transports some substances across the cell membrane.

• Since energy is consumed, substance can be moved across a concentration gradient.

• This mechanism is believed to be mediated by globular proteins in the membrane and requires energy.

Steps of Aqueous formation

1. Formation of stromal pool2. Active transport of stromal filtrates3. Passive transport across non-pigmented ciliary

epithelium

Formation of stromal pool

Active transport of stromal filtrates

• Tight junction between the non-pigmented epithelial cells create part of blood-aqueous barrier

• Evidence of active transport occurs due to:i. Abundant Na/K ATPaseii. Presence of more mitochondriaiii. Higher adenyl cyclase activityiv. Higher specific activity of glycolytic enzymesv. Preferential incorporation of labelled sulphate and

macromolecules (primarily glycolipids and glycoproteins).

Following substance from the stromal filtrates are actively transported across epithelial cells• sodium: approx 70% actively transported by a specific

secretory pump. Remaining 30% by diffusion or ultrafiltration. Active transport is ATPase dependent . Carbonic anhydrase acts to maintain the proper PH for the Na/K ATPase system.

• Chloride: major % by diffusion and small % by active transport and this appears to be dependent upon the presence of Na and PH

• Potassium: by secretion and diffusion• Ascorbic acid: secreted against large conc. gradient• Amino acids: secreted by 3 carriers, one each for acidic,

basic and neutral molecules• Bicarbonates: formation is catalyzed by carbonic anhydrase.

It influences fliud transport through its effect on sodium.

Passive transport across non-pigmented ciliary epithelium

• Active transport of the substance across the non-pigmented epithelium results in an osmotic and electrical gradient.

• To maintain the balance of osmotic and electrical forces, water, chloride and other small plasma constituent then move into the post chamber by ultrafiltration and diffusion

• Sodium is primarily responsible for movement of water into the posterior chamber and its secretion is a major factor in the formation of aqueous

Evidence about the secretion of sodium is the key factor in aqueous formation are:• Presence of large conc. of Na/K ATPase especially at

the lateral interdigitations of the non-pigmented layer

• Oubain which is an inhibitor of Na/K ATPase effectively reduces aqueous formation

• Shrinkage of ciliary processes is inhibited by oubain• Sodium accumulates in the post chamber after

parenteral administration of radioactive Na.

Rate of Aqueous Humor production

• 2-2.5microlitres/min

Methods of measurement

Class 1 method

Fluorescein technique

Radioactive labelled isotope

IV PAH or fluorescein

Class 2 method

Perfusion of eyes

Tonography Perilimbal suction cup

method

Control of Aqueous formation

1. Adrenergic innervation2. Role of vasopressin3. Role of adenylcyclaseCAMP activates specific protein kinase and thereby

results in specific protein phosphorylationprotein kinase activity induced by CAMP may cause a

change in permeability of non-pigmented epithelium4. Ultrafiltration and diffusion

Aqueous Humor drainage mechanism

• Uveoscleral (unconventional) outflow-pressure independent

• Trabecular (conventional) outflow

Uveoscleral outflow

Trabecular outflow

Various mechanism of Aqueous transport across schlemm’s canal

• Vacuolation theory• Leaky endothelial cells• Sonderman’s channels• Contractile microfilaments• Pores in endothelial cells

Vacuolation theory

Alteration of Aqueous in disease(secondary aqueous)

Intraocular malignancy• Plasma : aqueous ratio of LDH >1.50 in retinoblastoma • <0.60 in rubeosis iridis, ROP and malignant melanoma

Uveitis• IgG increase , IgM & IgA becomes detectable• Ab against toxoplasma gondii & toxocara canis

Retinal disease:• Photoreceptor cells in Aqueous and TB ---glaucoma associated with

rhegmatogenous RD

Glaucoma:• Heavy molecular weight soluble protein--- phacolytic glaucoma

FACTORS CAUSING DECREASE AQUEOUS• Hypothermia• Acidosis• Injection of hyperosmotic solution• Drugs: halothane, barbiturates, ketamine, vasopressin• Retinal detachment• Ocular inflammation

FACTORS CAUSING INCREASE IN AQUEOUS• Hyperthermia• Alkalosis• Injection of prostaglandins, arachidonic acid, hypo osmotic solutions,

calcium

Factors Affecting The Aqueous Out Flow• Age : modest decline with age• Hormones – corticosteroid decrease– progesterone,thyroxin ,prostaglandinsincrease

• Ciliary muscle tone: increased tone –increase• Drugs : prostaglandin analogs, alpha2 agonists• Surgical therapy: argon laser trabeculoplasty –improves;

cataract and PK reduces• Diurnal fluctuation :controversy

References

• American Academy of Ophthalmology-sec 10• Adler’s physiology of the Eye-9th edition• Anatomy and physiology of eye -2nd edition