Physiology of aqueous humor of eye

1. PHYSIOLOGY OF
AQUEOUS HUMOR
&
FACTORS MAINTAINING
NORMAL IOP
PRESENTED By Dr Rohit Rao

2. AQUEOUS HUMOR
• Clear, colorless fluid that fills the anterior and
posterior chambers of the eye.

3. Physiological properties
• Volume 0.31ml
• Refractive index 1.333
• PH 7.2
• Hyper osmotic
• Rate of formation 1.5 to 4.5 µl/min

4. Composition
• Water constitutes 99.9% of Normal Aqueous
• Proteins (5-16mg/100ml) concentration in Aqueous is
less than 1% of its plasma concentration
• 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
• Ascorbic acid concentration is very high in aqueous.
• Various components of the coagulation and
anticoagulation pathways may be present in human
aqueous humor.

5. Functions of aqueous
humor
• Brings oxygen and nutrients to cells of lens, cornea, iris
• Removes products of metabolism and toxic substances
from those structures
• Provides optically clear medium for vision
• Inflates globe and provides mechanism for maintaining
IOP
• High ascorbate levels protect against ultravioletinduced oxidative products, e.g., free radicals
• Facilitates cellular and humoral responses of eye to
inflammation and infection

6. The blood–aqueous barrier
• 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

7. • 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.

8. Stimuli that break blood–aqueous barrier

9. Aqueous humor dynamics
• Secreted by ciliary epithelium lining the ciliary processes
• Enters the posterior chamber.
• It then flows around the lens and through the pupil into
the AC.
• There is convection flow of aqueous in the AC due to
temperature gradiant.
• It leaves the eye by two pathways at the anterior
chamber angle:
– Through the TM, across the inner wall of Schlemm's
canal into its lumen, and thence into collector
channels, aqueous veins, and the episcleral venous
circulation – the trabecular or conventional route
– Across the iris root, uveal meshwork, and the anterior
face of the ciliary muscle, through the connective
tissue between the muscle bundles, the
suprachoroidal space, and out through the sclera –
the uveoscleral or unconventional route.

11. Aqueous humor formation
• Aqueous humor is produced from
pars plicata along the crests of the
ciliary processes.
Lens
• Aqueous humor is derived from
plasma within the capillary network
of the ciliary processes.
• Three physiologic processes
contribute to the formation and
chemical composition of the
aqueous humor:
– Diffusion
– Ultrafiltration
– Active secretion.
Pars
plicata

12. 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.

13. Ultrafiltration
• The process by which fluid and its solutes
cross semipermeable membrane under
pressure gradient is called ultrafiltration.
• As blood passes through capillaries of the
ciliary processes, about 4% of the plasma
filters through capillary wall into the
interstitial spaces between the capillaries
and the ciliary epithelium.
• In the ciliary body, fluid movement is
favored by the hydrostatic pressure
difference between the capillary pressure
and the interstitial fluid pressure and is
resisted by the difference between the
oncotic pressure of the plasma and the
aqueous humor.

14. 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

15. Basic Physiologic
Processes
• Accumulation of Plasma Reservoir
– Most plasma substances pass easily from the
capillaries of the ciliary processes, across the stroma,
and between the pigmented epithelial cells before
accumulating behind the tight junctions of the
nonpigmented epithelium.
– This movement takes place primarily by diffusion and
ultrafiltration.

16. • 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 bloodaqueous 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.

17. – 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.
• Osmotic Flow
– The osmotic gradient across ciliary epithelium, results
from active transport
– It favors the movement of other plasma constituents
by ultrafiltration and diffusion.

18. Biochemistry of aqueous humor
formation
• The structural basis for
aqueous humor secretion
is the bilayered ciliary
epithelium.(pigmented
epithelium & nonpigmented epithelium )
• The active process of
aqueous secretion is
mediated by two
enzymes present in the
NPE: Na+-K+-ATPase and
carbonic anhydrase

19. 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.

21. 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

22. – 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.

25. • Episcleral and Conjunctival Veins The Schlemm
canal is connected to episcleral and
conjunctival veins by a complex system of
intrascleral channels.
• Two systems of intrascleral channels have been
identified:
– A direct system of large caliber vessels, with short
intrascleral course, drain into episcleral venous
system
– An indirect system of more numerous, finer channels,
which form an intrascleral plexus before draining into
episcleral venous system.

27. Pumping model for
trabecular outflow
• The aqueous outflow pump receives power
from transient increases in IOP such as occur in
systole of the cardiac cycle, during blinking and
during eye movement.

28. The biomechanical pump model. Powered by transient increases
in IOP, caused by cardiac cycle, blinking & eye movements. As
pressure increases, fluid is forced into one-way collector valves
(C) that span across Schlemm’s canal. At the same time, the
increase in IOP pushes the endothelium of the inner wall of
Schlemm’s canal (A, B) outward and forces aqueous in the
canal to move circumferentially into collector channels and
aqueous veins. As the pressure drops, the tissues rebound,
causing a pressure drop inside Schlemm’s canal, moving fluid
from the one-way valves (C) into the canal.

29. • Active involvement of the TM in regulating
outflow
– The cellular component of the conventional outflow
pathway: Schlemm’s canal endothelia,
juxtacanalicular cells, endothelium lining the lumen of
Schlemm’s canal valves, and endothelium lining
trabecular lamellae.
• The TM is suspended between two fluid
compartments (anterior chamber and
Schlemm’s canal) at different pressures.
• The TM can “sense” the pressure differential
and strives to maintain these parameters within
a homeostatic range.

30. Theory of transcellular aqueous transport in which a series of pores and giant
vacuoles opens (probably in response to transendothelial hydrostatic pressure)
on the connective tissue side of the juxtacanalicular meshwork (2–4). Fusion of
basal and apical cell plasmalemma creates a temporary transcellular channel
(5) that allows bulk flow of aqueous into Schlemm’s canal.

31. 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

32. • 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.

33. FACTORS EXERTING LONG-TERM
INFLUENCE ON IOP
• Genetics
• Age
• Gender
• Refractive Error
• Ethnicity

34. Genetics
• The IOP is under hereditary influence.
• IOP tends to be higher in individuals
with enlarged CDR & in those who
have relatives with open-angle
glaucoma.

35. • IOP increases with age.
• Studies indicate that children
have lower pressures than the rest
of the normal population,
Age
• But tonometric measurements
may be influenced by the level of
cooperation of the child,
tonometer used, use of general
anesthesia or a hypnotic agent.
• There may be a positive
independent correlation between
IOP and age & may be related to
reduced facility of aqueous
outflow & decreased aqueous
production.

36. • Gender
– IOP is equal between the sexes in ages 20 to 40 years.
– In older age groups, the apparent increase in mean IOP
with age is more in women.
• Refractive Error
–
A positive correlation between IOP and both axial
length of the globe and increasing degrees of myopia
– Myopes also have a higher incidence of COAG
Ethnicity
Blacks have been reported to have slightly
higher pressures than whites.

37. FACTORS EXERTING SHORT-TERM
INFLUENCE ON IOP
• Diurnal
• Postural Variation
• Exertional Influences
• Lid and Eye
Movement
• Intraocular Conditions
• Systemic Conditions
• Environmental
Conditions
• General Anesthesia
• Foods and Drugs

38. Diurnal Variation
• IOP shows cyclic fluctuations throughout the day.
• Ranges from approximately 3 mm Hg to 6 mm Hg.
• Higher lOP is associated with greater fluctuation,
and a diurnal fluctuation of greater than 10 mm Hg
is suggestive of glaucoma.
• The peak IOP is in the morning hours
• Primary clinical value of measuring diurnal IOP
variation is to avoid the risk of missing a pressure
elevation with single readings.

39. Postural Variation
• The IOP increases when changing from the
sitting to the supine position, average pressure
differences of 0.3 to 6.0 mm Hg.
• The postural influence on IOP is greater in eyes
with glaucoma and persists even after a
successful trabeculectomy.
• Patients with systemic hypertension have
greater IOP increase after 15 minutes in supine

40. Exertional Influences
• Exertion may lead to either a lowering or an
elevation of the IOP, depending on the nature
of the activity.
• Prolonged exercise, such as running or bicycling,
has been reported to lower the IOP.
• The magnitude of this pressure response is greater in
glaucoma patients than in normal individuals.
• Straining, as associated with the Valsalva
maneuver, electroshock therapy, or playing a wind
instrument, has been reported to elevate the IOP.
• May be due to elevated episcleral venous pressure
and increased orbicularis tone.

41. Lid and Eye Movement
• Blinking has been shown to rise the IOP 10 mm
Hg, while hard lid squeezing may raise it as high
as 90 mm Hg.
• Contraction of extraocular muscles also
influences the IOP.
• There is an increase in IOP on up-gaze in normal
individuals, which is augmented by Graves'
infiltrative ophthalmopathy.

42. Intraocular Conditions
• Elevated IOP is with associated glaucoma
• IOP may be reduced in Anterior uveitis,
Rhegmatogenous retinal detachment

43. Systemic Conditions
• Positive correlation between systemic hypertension,
• Systemic hyperthermia has been shown to cause an increased
IOP.
• IOP may increase in response to ACTH, glucocorticoids, and
growth hormone and it may decrease in response to
progesterone, estrogen, chorionic gonadotropin, and relaxin.
• It is significantly reduced during pregnancy, may be due excess
progesterone.
• IOP is lower in hyperthyroidism and higher in hypothyroidism.
• In myotonic dystrophy, the IOP is very low, which may be due
to reduced aqueous production & increased outflow.
• Diabetic patients have higher pressures than the general
population, while a fall in IOP is seen during acute
hypoglycemia.
• Patients with HIV have lower than normal mean IOPs

44. • Environmental Conditions
– Exposure to cold air reduces IOP, apparently because episcleral
venous pressure is decreased. Reduced gravity causes a sudden,
marked increase in IOP.
• General Anesthesia
– General anesthesia reduces the IOP,
– Exceptions are trichloroethylene and ketamine which elevate the
ocular pressure.
– In infants and children GA can mask a pathologic pressure elevation.
– Hypnotics that are used to produce unconsciousness, such as 4hydroxybutyrate and barbiturates and tranquilizers reduce the IOP
– Depolarizing muscle relaxants, such as succinylcholine and
suxamethonium cause a transient increase in IOP, possibly due to a
combination of extraocular muscle contraction and intraocular
vasodilation.
– Tracheal intubation may also cause an IOP rise.
– Elevated pCO2causes an increase in IOP, whereas reduced pCO2 or
increased concentration of O2 is associated with an IOP reduction.

45. Foods and Drugs
• Alcohol has been shown to lower the IOP,
more so in patients with glaucoma.
• Caffeine may cause a slight, transient rise in IOP.
•
A fat-free diet has been shown to reduce IOP, which
may be related to a concomitant reduction in plasma
prostaglandin levels.
• Tobacco smoking may cause a transient rise in the IOP,
and smokers have higher mean IOPs than nonsmokers
•
Heroin and marijuana lower the IOP, while LSD(lysergic
acid diethylamide) causes an IOP elevation.
• Corticosteroids may also cause IOP elevation.

46. THANK
U