Aqueous Humour Dynamics

AQUEOUS HUMOUR DYNAMICS
Dr Prasanta Kumar Sahoo

INTRODUCTION
 Flow of aqueous humour against resistance generates an IOP of
about 15 mm Hg, which is necessary for the proper shape and
optical properties of the globe.
 Aqueous humour dynamics plays an important role in development
of pathophysiological mechanism of Glaucoma.
 AH- clear ,colourless , watery solution
 Flows from posterior chamber to anterior chamber
 Nutrition to lens, cornea and iris
 Removes metabolically toxic products by active transport system.
 Refractive index- 1.33
 Inflates globe and maintains IOP
 Ascorbate-antioxidant-UV protection
 Facilitates cellular and humoral response of eye to inflammation and
infection

PHYSIOLOGICAL PROPERTIES
Volume 0.31ml
Refractive index 1.333
PH 7.2
Hyper osmotic
Rate of formation 2.0 to 2.5 µl/min

COMPOSITION
 Water constitutes 99.9% of Normal Aqueous
 Proteins (5-16mg/100ml) concentration in Aqueous, is less than 1% of its
fluid concentration
 200 times less protein and 20 times more ascorbic acid than plasma.
 Glucose – 75% of the plasma concentration.
 Electrolytes:
 Na+  similar in plasma and aqueous
 Bicarbonate ion: Concentration  in PC &  in AC
 Cl ion concentration  than plasma and phosphate concentration  than
plasma
 IgG is more than IgM and IgA
 Viscosity and density is slightly higher than water.
 Hyaluronic acid- protective against clogging of outflow tract.
 TGF-β – transformin Growth Factor plays an important role in glaucoma
pathogenesis.

DYNAMICS
Aqueous humour dynamics
include:
Anatomy of aqueous humour
formation and drainage structures
Aqueous humour formation
Aqueous humour drainage.

ANATOMY
Primary ocular structures involved are
1. Cilliary body
2. Posterior chamber
3. Anterior chamber
4. Angle of anterior chamber
5. Aqueous outflow system

CILIARY BODY
 Seat of aqueous production
 Triangular in shape
 Outer side- line with sclera with a supra choroidal space in
betweeen
 Inner side of ciliary body has two parts-
a) Anteriorly pars plicata(finger like projections-ciliary process)
b) Posteriorly pars plana
 Ciliary muscle- non striated muscle -3 parts
1. Longitudinal or meridional fibers- helps in aqueous outflow
2. Circular muscles- helps in accomodation
3. Radial or oblique fibers- helps in aqueous out flow

CILIARY PROCESSES
 70-80 Whitish finger like projections
 Composed of central capillary network with fenestrated
thin endothelium and pericytes surrounded by stroma
and two layers of epithelium and ILM.
 Inner nonpigmented (NPE) and outer pigmented
epithelium (PE)
 Outer epithelium is continuation of RPE
 Inner epithelium is continuation of neurosensory retina.
 Outer PE- gap junction, desmosomes between cells.
 Inner NPE characterized by mitochondria, zonula
occludens (ZO)and lateral surface interdigitations
 The tight junctions(Zona occludens) contribute to the
blood aqueous barrier

BLOOD AQUEOUS BARRIER(BAB)
• Barriers to the movement of substances from the plasma to the
aqueous humor.
• In the ciliary body the barriers include
– Vascular endothelium
– Stroma
– Basement membrane
– Pigmented and non-pigmented epithelium.
Zona occludens

The blood–aqueous barrier is responsible for
differences in chemical composition between the
plasma and the aqueous humor.
Breakdown of blood aqueous barrier
In some situations (e.g., intraocular infection)- a
breakdown of the blood–aqueous barrier is clearly
therapeutic
In other situations (e.g., some forms of uveitis and
following trauma), the breakdown of the barrier
leads to complications.

ANTERIOR CHAMBER
 2.5mm deep in centre,
 Contains 0.25ml aqueous
 Bounded
 anteriorly-post surface of cornea,
 Posteriorly- anterior surface of ciliary body and iris
 Comunicates through the pupil with post. Chamber
 Chamber volume decreases by 0.11μl/year of life
 Chamber depth decreases by 0.01mm/year of life
 Chamber depth is shallower in hypermtropic than myopic
 Chamber depth is slightly decrease during accommodation
partly by lens curvature and partly by forward
translocation of lens.

ANGLE OFANTERIOR CHAMBER
Formed by iris root, anterior part of ciliary body,
scleral spur ,trabecular meshwork and Schwalbe’s
line.
Anteriorly- schwalbe’s line
Posteriorly-iris
Major drainage pathway for aqueous humour.
Also known as filtration angle or iridocorneal angle.
Angle is wider in myopic eyes and narrow in
hypermetropes.

AQUEOUS FORMATION
Complex pathway
Ciliary processes are site of aqueous
humour production
Mainly by thee mechanisms
1. Ultrafiltration-20%
2. Active secretion-70%
3. Diffusion-10%

DIFFUSION
 Diffusion is the movement of substance across a
membrane along concentration gradient.
 As aqueous humor passes from the PC to Schlemm’s
canal, it is in contact with ciliary body, iris, lens, vitreous,
cornea, and trabecular meshwork.
 There is diffusional exchange, so that the AC aqueous
humor resembles plasma.

ULTRAFILTRATION
Also known as relative dialysis.
The process by which the fluid and
solutes cross through the
semipermiable membrane.
Capillary blood flow-150 ml/min
4% through fenestrations
Favoured by hydrostatic pressure
difference between capillary and
interstitial pressure.
Enough to move fluid to stroma but
further requiered active transport.
Leads to form stromal pool
Dialysis
Ultrafiltration

ACTIVE TRANSPORT
Active transport is energy-dependent process that
selectively moves substance against its
electrochemical gradient across a cell membrane.
It is postulated that majority of aqueous humor
formation depends on active transport.
It is done by non-pigmented epithelial cells
Involves electrochemical and biochemical
process.

Transport across Blood-Aqueous Barrier
 Active secretion is a major contributor to aqueous
humor formation.
 Selective transcellular movement of certain cations,
anions, and other substances across the blood-aqueous
barrier formed by the tight junctions between the
nonpigmented epithelium.
 Aqueous humor secretion is mediated by transferring
NaCl from ciliary body stroma to PC with water
passively following.
 Carbonic anhydrase mediates the transport of
bicarbonate across the ciliary epithelium through a
rapid interconversion between HCO-
3 and CO2.
 Other transported substances include ascorbic acid,
which is secreted against a large concentration
gradient by the sodium-dependent vitamin C
transporter 2.(SVCT2)

BIOCHEMISTRY OF AH FORMATION
 The structural basis for aqueous humor secretion is the
bilayered ciliary epithelium.(pigmented epithelium &
non-pigmented epithelium )
 The active process of aqueous secretion is mediated by
two enzymes present in the NPE: Na+-K+-ATPase and
carbonic anhydrase.(CA)
 ATP ADP+Pi
 CO2 + H2O →I H2CO3 →II H+ + HCO3-
 I reaction is facilitated by CA
 II reaction is spontaneous

MATHEMATICAL EQUATION OF A.H FORMATION
MODIFIED GOLDMANN EQUATION
 Pe- episcleral venous
pressure
 Fin –aqueous flow
 Fu- Uveoscleral flow
 Ctrab- Trabecular
meshwork flow

PHARMACOLOGY AND REGULATION
 Sympathetic and parasympathetic nerve terminals are present in the ciliary body
and arise from branches of the long and short posterior ciliary nerves.
 Parasympathetic fibers originate in the Edinger-Westphal nucleus of the third
cranial nerve.
 Sympathetic fibers synapse in the superior cervical ganglion and are distributed
to the muscles and blood vessels of the ciliary body.
 Sensory fibers arise from the ophthalmic division of the trigeminal nerve and
enter the ciliary body.
Cholinergic or Parasympathetic Mechanisms- Not clear but species related.
 Choloinergic- increase AHF( by vaso dilation, loss of tight junctions and
breakdown of BAB, e.g pilocarpine)
 Adrenergic mechanism
 Adrenergic agonists increase AHF e.g epinephrine, salbutamol,isoproterenol
(isoprenaline),and terbutaline.
 β-adrenergic antagonists (β blocker) decrease AHF. e.g Timolol

AQUEOUS HUMOR OUTFLOW
 The aqueous humor leaves the eye at the anterior chamber
angle through trabecular meshwork, the Schlemm’s canal,
intrascleral channels, and episcleral and conjunctival veins.
 This pathway is referred to as the conventional or trabecular
outflow.
 In the unconventional or uveoscleral outflow, aqueous
humor exits through the root of iris, between the ciliary
muscle bundles, then through the suprachoroidal - scleral
tissues.
 Trabecular outflow accounts for 70% to 95% of the aqueous
outflow .
 And remaining 5% to 30% by uveoscleral outflow.

FACTORS REDUCE AH SECRETION
 Age
 Diurnal cycle
 Exercise
 Reduction in Blood pressure
 Hypothermia
 Acidosis
 General Anaesthesia
 Plasma hyperosmolality
 Cyclic GMP
 Spironolactone
 Increased IOP(Pseudofacility)
 Uveitis(specially Iridocyclitis)
 β-Adrenoreceptor antagonists (e.g.,
timolol, betaxolol, levobunolol,
carteolol, metipranolol).
 Carbonic anhydrase inhibitors.
 Nitrovasodilators; atrial natriuretic
factor(ANF)
 Calcium channel antagonists
 DA2 agonists (e.g., pergolide,
lergotrile, bromocriptine)
 ACE inhibitors
 Cardiac glycosides (e.g., ouabain,
digoxin , Vanadate)

Cellular Organization of the
Trabecular Outflow Pathway
 Scleral Spur The posterior wall of the scleral sulcus
formed by a group of fibers, the scleral roll, which run
parallel to the limbus and project inward to form the
scleral spur.
 Schwalbe Line Anterior to the apical portion of the
trabecular meshwork is a smooth area called as zone S.
The posterior border is demarcated by a discontinuous
elevation, called the Schwalbe line
 Trabecular Meshwork :The scleral sulcus is converted
into a circular channel, called the Schlemm canal, by the
trabecular meshwork. It may be divided into three
portions: (a) uveal meshwork; (b) corneoscleral
meshwork; and (c) juxtacanalicular tissue

– Uveal Meshwork This innermost portion is adjacent
to aqueous humor in the AC and is arranged in
ropelike trabeculae that extend from iris root and
ciliary body to peripheral cornea.
– Corneoscleral Meshwork This portion extends from
the scleral spur to the anterior wall of the scleral
sulcus .
– Juxtacanalicular Tissue This structure has three
layers. The inner trabecular endothelial layer is
continuous with the endothelium of corneoscleral
meshwork. The central connective tissue layer &
outermost portion is the inner wall endothelium of
the Schlemm canal.

VACUOLATION THEORY OF AQUEOUS TRANSPORT
ACROSS SCHLEMM’S CANAL
Vacuolation theory of aqueous
transport across the inner wall of
the Schlemm's canal:
1. Non-vacuolated stage.
2.Stage of early infolding of
basal surface of the endothelial
cell.
3. Stage of macrovacuolar
structure formation.
4. Stage of vacuolar transcellular
channel formation.
5.Stage of occlusion of the basal
infolding

CELLULAR ORGANIZATION OF THE
UVEOSCLERAL PATHWAY
 Two unconventional pathways have been discriminated: (a) through
the anterior uvea at the iris root, uveoscleral pathway, and (b)
through transfer of fluid into the iris vessels and vortex veins, which
has been described as uveovortex outflow.
 Uveoscleral Outflow
Studies have shown aqueous humor passes through the root of
the iris and interstitial spaces of the ciliary muscle to reach the
suprachoroidal space. From there it passes to episcleral tissue via
scleral pores surrounding ciliary blood vessels and nerves,
vessels of optic nerve membranes, or directly through the
collagen substance of the sclera.
 Uveovortex Outflow
Tracer studies in primates have also demonstrated unidirectional
flow into the lumen of iris vessel by vesicular transport, which is
not energy dependent. The tracer can penetrate vessels of the iris,
ciliary muscle, and anterior choroid to eventually reach the
vortex veins

 The uveoscleral pathway is characterized as “pressure independent,”
 It is reduced by cholinergic agonists, aging, and is enhanced by
prostaglandin drugs.
 A potential explanation for the observed decline in uveoscleral
outflow with aging is thickening of elastic fibers in the ciliary
muscles.
PHARMACOLOGY OF OUTFLOW
 CHOLINERGIC MECHANISM
 Cholinergic agonist decrease outflow resistance in TM outflow(iris-
ciliary muscle contraction-leads to alteration in TM configuration)-
Increase out flow-decrease IOP
 In UVEOSCLERAL out flow- muscle contraction reduces space
between muscle bundles cause reduction in outflow.

 ADRENERGIC MECHANISM
 Trabecular outflow facility increases in response to β-
adrenergic agonists
 Intracameral epinephrine increase outflow facility
 Trabecular cells synthesize cyclic AMP in response to
stimulation with β-adrenoceptor-selective agonists.
 β-Adrenergic receptors are present in ciliary muscle, and
their physiologic or pharmacologic stimulation relaxes
the muscle and thereby more inter muscular space and
increase UVEOSCLERAL OUTFLOW

Aqueous Humour Dynamics

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