aqueous humor

1. PHYSIOLOGYOF
AQUEOUS HUMOR
&
FACTORSMAINTAINING
NORMAL IOP
PRESENTED By Dr Rohit

2. AQUEOUSHUMOR
• Clear, colorless fluid thatfillsthe anteriorand
posteriorchambers of the eye.

3. Physiological properties
• Volume 0.31ml
• Refractive index 1.333
• PH 7.2
• Hyper osmotic
• Rateof formation 1.5to4.5 µl/min

4. Composition
• Waterconstitutes99.9%of Normal Aqueous
• Proteins(5-16mg/100ml)concentration inAqueous is
lessthan 1
%
of itsplasma concentration
• Glucose –7
5
%of the plasma concentration.
• Electrolytes:
– Na+ similarinplasma and aqueous
– Bicarbonate ion: Concentration  in PC &  in AC
– Cl ion concentration  than plasma and phosphate
concentration  than plasma
• Ascorbic acid concentration isvery high in aqueous.
• Various components of the coagulation and
anticoagulation pathways may be presentinhuman
aqueous humor.

5. Functionsofaqueous
humor
• Bringsoxygen and nutrientstocells oflens,cornea, iris
• Removes products ofmetabolismand toxic substances
fromthose structures
• Providesoptically clear medium for vision
• Inflatesglobe and provides mechanism formaintaining
IOP
• Highascorbate levels protect against ultraviolet-
induced oxidative products, e.g., free radicals
• Facilitates cellular and humoralresponsesofeye to
inflammationand infection

6. Theblood–aqueous barrier
• Barrierstothe movement of substances fromthe plasma tothe
aqueous humor.
• Inthe ciliary body thebarriers include
– Vascular endothelium
– Stroma
– Basement membrane
– Pigmented and non-pigmented epithelium.
Zonaoccludens

7. • Theblood–aqueous barrierisresponsible
fordifferences inchemical composition
between the plasma and the aqueous
humor.
• Breakdown of blood aqueous barrier
– Insome situations(e.g., intraocular
infection), a breakdown of the blood–
aqueous barrierisclearly therapeutic
– Inother situations (e.g., some forms of uveitis
and following trauma), the breakdown of the
barrierleads to complications.

8. Stimulithatbreak blood–aqueous barrier

9. Aqueous humor dynamics
• Secreted by ciliary epitheliumlining theciliary processes
• Enterstheposterior chamber.
• I
tthenflowsaround thelensand throughthepupil into
the AC.
• Thereisconvection flowof aqueous in the AC due to
temperature gradiant.
• I
tleaves theeye by twopathwaysat theanterior
chamber angle:
– ThroughtheTM,across theinnerwallof Schlemm's
canal intoitslumen,and thence intocollector
channels, aqueous veins, and theepiscleral venous
circulation –thetrabecular orconventional route
– Across theirisroot,uveal meshwork,and the anterior
face of theciliary muscle, throughthe connective
tissuebetween themuscle bundles, the
suprachoroidal space, and outthroughthesclera –
theuveoscleral orunconventional route.

11. Aqueous humor formation
• Aqueous humorisproduced from
pars plicata along thecrestsof the
ciliary processes.
• Aqueous humorisderived from
plasma withinthe capillarynetwork
ofthe ciliary processes.
• Threephysiologic processes
contribute totheformation and
chemical composition ofthe
aqueous humor:
– Diffusion
– Ultrafiltration
– Active secretion.
Lens
Pars
plicata

12. Diffusion
• Diffusionisthe movement of substance across a
membrane along concentration gradient.
• As aqueous humorpassesfromthe PC to
Schlemm’s canal, itisincontact withciliary
body, iris,lens, vitreous,cornea, and trabecular
meshwork.
• Thereisdiffusional exchange, sothatthe AC
aqueous humorresembles plasma.

13. Ultrafiltration
• Theprocess by whichfluidand itssolutes
crosssemipermeable membrane under
pressuregradient iscalled ultrafiltration.
• Asblood passes through capillaries of the
ciliary processes, about 4
%
ofthe plasma
filtersthroughcapillary wallinto the
interstitialspaces between thecapillaries
and theciliary epithelium.
• Intheciliary body, fluidmovement is
favored by the hydrostatic pressure
difference between thecapillary pressure
and theinterstitialfluidpressureand is
resistedby thedifference between the
oncotic pressureofthe plasma and the
aqueous humor.

14. Active transport
• Active transportisenergy-dependent process
thatselectively moves substance against its
electrochemical gradient across a cell
membrane.
• I
tispostulated thatmajorityof aqueous humor
formationdepends on active transport.
• I
tisdone by non-pigmented epithelial cells

15. Basic Physiologic
Processes
• Accumulation of Plasma Reservoir
– Mostplasma substances passeasily fromthe
capillaries of theciliary processes, across thestroma,
and between thepigmented epithelial cells before
accumulating behind thetightjunctions of the
nonpigmented epithelium.
– Thismovement takes place primarilyby diffusionand
ultrafiltration.

16. • Transportacross Blood-Aqueous Barrier
– Active secretion isa majorcontributor to aqueous
humorformation.
– Selective transcellular movement of certain cations,
anions, and othersubstances across theblood-
aqueous barrierformedby thetightjunctions
between thenonpigmented epithelium.
– Aqueous humorsecretion ismediated by transferring
NaCl from ciliary body stromatoPC withwater
passively following.

17. – Carbonic anhydrase mediates thetransportof
bicarbonate across theciliary epitheliumthrougha
rapid interconversion between HCO-
3 and CO2.
– Othertransported substances include ascorbic acid,
which issecreted against a large concentration
gradient by thesodium-dependent vitaminC
transporter2.
• Osmotic Flow
– Theosmotic gradient across ciliary epithelium, results
fromactive transport
– I
tfavorsthemovement of otherplasma constituents
by ultrafiltrationand diffusion.

18. • Thestructuralbasis for
aqueous humorsecretion
isthebilayered ciliary
epithelium.(pigmented
epithelium & non-
pigmented epithelium )
• Theactive process of
aqueous secretion is
mediated by two
enzymespresentinthe
NPE:Na+-K+-ATPaseand
carbonic anhydrase
Biochemistryof aqueous humor
formation

19. AQUEOUS HUMOR
OUTFLOW
• Theaqueous humorleaves theeye at the anterior
chamber angle throughtrabecular meshwork, the
Schlemm’scanal, intrascleral channels, and
episcleral and conjunctival veins.
• Thispathway isreferredtoas the conventional or
trabecular outflow.
• Intheunconventional oruveoscleral outflow,
aqueous humorexitsthroughtheroot ofiris,
between theciliary muscle bundles, thenthrough
thesuprachoroidal - scleral tissues.
• Trabecular outflowaccounts for7
0
%to9
5
%ofthe
aqueous outflow .
• And remaining 5
%
to3
0
%by uveoscleral outflow.

21. Cellular Organization ofthe
Trabecular Outflow Pathway
• Scleral SpurTheposteriorwallof thescleral sulcus formed by a
group of fibers,the scleral roll,which runparallel tothe limbus
and project inwardtoformthe scleral spur.
• Schwalbe LineAnterior tothe apical portionof thetrabecular
meshworkisa smootharea called as zone S.Theposterior
border isdemarcated by a discontinuous elevation, called the
Schwalbe line
• Trabecular MeshworkThescleral sulcus isconverted intoa
circular channel, called theSchlemm canal, by the trabecular
meshwork.I
tmay be divided intothreeportions:(a)uveal
meshwork;(b)corneoscleral meshwork;and (c)
juxtacanalicular tissue

22. – Uveal MeshworkThis 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 MeshworkThis portion extends from the
scleral spur to the anterior wall of the scleral sulcus.
– Juxtacanalicular TissueThis 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,
• 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.
Age

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 4-
hydroxybutyrate 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. TH
AN
KU