SEMINAR ON AQUEOUS HUMOR

TESFALEM
HAGOS(MD)

MAY 2003
07/15/2021 1
 OUT LINE
 Function of aqueous humor
 Production
 IOP
 Composition
 Anterior angle structures
 Anatomy of out flow
 Aqueous out flow

07/15/2021 2
 AQUEOUS HUMOR

 Transparent & clear solution.

Provides
 Takes the place of lymphs
 Nourishes adjacent structures
 Removes metabolic wastes
 Maintains appropriate lOP
 Provides optically clear medium

07/15/2021 3
 PRODUCTION
 Secreted at a rate of 2-3 micL/min,turned over
1%/min.
 Anterior chamber 0.25 ml and posterior

chamber 0.06 ml
 Formed byciliary processes

 Rich supply of fenestrated capillaries(MACI)

 Has tight junctions, blood aqueous barrier
 Contain numerous mitochondria and microvilli

07/15/2021 4
 Rate of aqueous formation is affected by :
• Integrity of blood-aqueous barrier
• Blood flow to ciliary body
• Neurohumoral regulation of vascular tissue and
ciliary epithetelium

07/15/2021 5
 Formation and chemical composition depend on:

- Ultrafiltration (dialysis)
- Active secretion
- Diffusion

07/15/2021 6
 DIFFUSION
 Passive ,requires no energy
 Occurs across cell membranes down concentration
gradient
 Till equilibrium reached, movement continues but no net
movement.
 Depends on
- Permeability to solute or solvent
- Temperature
- Viscousity

07/15/2021 7
DIALYSIS AND ULTRAFILTRATION
 Hydrostatic pressure driven flow

 Net movement of water to protein side and movement of

salt away from protein side-dialysis

 Increase rate of movement of ions because of hydrostatic

pressure-ultrafiltration

 Due to higher pressure and protein in plasma compared

to extracellular space

07/15/2021 8
07/15/2021 9
07/15/2021 10
 GIBBS-DONNAN EQUILIBRIUM
 Altered distribution of ions at equilibrium
 Higher concentration of cations on protein side
higher concentration of anions on nonprotein
side

07/15/2021 11
07/15/2021 12
 Expectations
- Protein-free aqueous solution
- Na+ and K+ less than plasma
- Cl- and HCO3- slightly higher
- no organic substance is higher than in plasma

 Do not fit to Gibbs-Donnan predictions BUT

dialysate of plasma
-Explained by active metabolic process

07/15/2021 13
07/15/2021 14
 SECRETION
 Active process selectively transports substances
across cell membrane.
 Move against concentration gradient.
 Evidences
- Higher ascorbate, lactate and AA than
plasma
- Metabolic inhibitors to ciliary body
- 70% reduction

07/15/2021 15
 Ciliary process stroma
- Oncotic pressure 14 mmHg(protein )
- IOP in healthy eye 16 mmHg
 Capillary hydrostatic pressure >30 mmHg
required to drive ultrafiltrate.
 So> 50 mmHg necessary to promote
ultrafiltration as major mechanism

07/15/2021 16
 Active transport systems in ciliary epithelium
- Na+ /K+ ATPase
- Amino acid membrane transporters
 Passive transport proteins
- HCO3- and Cl-

07/15/2021 17
 Pigmented and nonpigmented epithelial cells of ciliary
processes-CA
 Nonpigmented ciliary epithelial cells, water to OH-
and H+

HO- + CO2

HCO3-

Passively transported to aqueous humor, with active

transport of Na+
07/15/2021 18
07/15/2021 19
 MECHANISMS

 Decrease in HCO3-
 Reduction in intracellular pH
 Decreased H+ produced by the reaction decreases
H+ /Na+ exchange
 Reduction in secretion and hence IOP, more than
99% of the enzyme must be inhibited

07/15/2021 20
 Na+ and K+ from plasma to posterior chamber
 HCO3-, Cl- and water follows passively to
maintain electrical and osmotic balance.
 ultrafiltrate of plasma in extravascular spaces of
ciliary stroma.
 selective active secretion (NPE) into posterior
chamber, whilst others secreted passively.

07/15/2021 21
INTRAOCULAR PRESSURE
 Pressure exerted by intraocular fluids on coats of
eyeball.
 Most have IOP 10 -22 mmHg (mean 16 ± 3 mm of
Hg).
 Po= F/C + Pe
F=2 micl/min
C=o.2 micl/min
Pe=10 mm hg

07/15/2021 22
 There is no clear lOP
level below which lOP
can be considered
normal or safe and above
which lOP
can be considered elevated
or unsafe.

07/15/2021 23
DETERMINING FACTORS
1. Rate of aqueous formation
 Permeability of ciliary capillaries
 Osmotic pressure of blood

2. Resistance to aqueous outflow (drainage)

 The most important factor
 Most of the resistance is at trabecular meshwork.

3. Increased episcleral venous pressure

4.Dilatation of pupil

07/15/2021 24
EPISCLERAL VENOUS PRESSURE

 Relatively stable(8-10 mm Hg)

 Alterated in
- Body position change
- Diseases of head and neck
- Shunt blood from arterial to venous system.
 In acute conditions IOP rises 1 mm Hg for every 1
mm Hg increase
 Result in collapse of schlemms canal

07/15/2021 25
 5.Heredity
6.Age
7.Sex
8.Diurnal variation
 Higher IOP in morning and lower in evening

- Normal eyes <5 mm Hg

- Glaucomatous eyes > 8 mm of Hg
9.Postural variations
10.Blood pressure

07/15/2021 26
11.Osmotic pressure of blood
 An increase in plasma osmolarity
 water drinking provocative tests

12.General anaesthetics
14.Antiglaucoma drugs

07/15/2021 27
 DRUGS INCREASING
 Tobacco ,smoking, caffeine and steroids
 Beta adrenergic agonists

07/15/2021 28
DRUGS REDUCING AQUEOUS
FORMATION
 adrenalectomy
 Spironolactone
 Hyperosmotic agents
 Beta blockers
 Ca- channel blockers
 Alcohol
 Carbonic anhydrase inhibitors
 Serotonin inhibitors
 ACE inhibitors
 Antihistamines
 Cardiac glycosides
 Alph2 agonists-apraclonidine,brimondine
07/15/2021 29
 RAISED IOP

07/15/2021 30
 BLOOD-AQUEOUS BARRIER
 Due to
1.Tight junctions between NPE cells
2.Tight junctions of endothelia in iris
 Restricts free passage of solutes from blood vessels
of ciliary stroma into aqueous humor  
 Large molecules like proteins are present in small
amount
 not absolute
 Passage depends on Water solublity, lipid solubility
& molecular wt

07/15/2021 31
 HYPEROSMOTIC AGENTS
 Mannitol.
 Glycerin
 Urea
 Isosorbide
 Ethanol
-Urea slowly penetrate blood-aqueous barrier,
and is shorter lived
-Ethanol penetrates eye even more rapidly than
urea and effects on sensorium

07/15/2021 32
 ANTIBIOTICS
 chloramphenicol, cephalothin, and ampicillin
penetrate blood-aqueous barrier well
  poorly penicillin, methicillin, erythromycin, and
gentamicin

07/15/2021 33
BREAK DOWN OF BLOOD-AQUEOUS
BARRIER
 Trauma
 Intraocular surgery
 Uveitis
 Inflammatory disorders….
 Protein increase 10- 100 X
 Inflammatory mediators
 Immunoglobulins ,fibrin, and proteases rise
 Balance among various growth factors is
disrupted
secondary or plasmoid aqueous
07/15/2021 34
MECHANISM
 vasodilation of iridial vessels
 Prostaglandins --breakdown of tight junctions
-Pretreatment with inhibitors of prostaglandin
synthesis ---indomethacin or aspirin inhibit
breakdown
-Small doses ---increase uveoscleral out flow

07/15/2021 35
 CONSEQUENCES
 Fibrinous exudate and clot
 Synechiae formation (peripheral and posterior)
 Abnormal neovascular response
 Hyperplasia of lens epithelium, corneal
endothelium,trabecular meshwork, and iris
 Complicated cataracts
 Degenerative and proliferative changes

07/15/2021 36
 - Anti-inflammatory steroidal and nonsteroidal
drugs
- Cycloplegics
- Protease activators or inhibitors
- Growth and antigrowth factor agents
- Surgical intervention

07/15/2021 37
AQUEOUS HUMOR COMPOSITION
 Determined by active secretion
 Similar to plasma but not an ultrafiltrate of plasma
 Ionic composition is determined by selective active-transport
Na+-K+-2Cl- symport
Cl—HCO3
Na-H+ antiports
cation channels
water channels
Na+-K+-ATPase
K+ channels
CI- channels
H+-ATPase
07/15/2021 38
 99.9% water,0.1% solid
 Ions ,electrolytes & different molecular mass.
 Synthesized locally in Ciliary epithelium and
secretion by NPE cells.
 Exhibits neuroendocrine propertiy determing
composition and regulation.
 In dynamic equilibrium, determined both by rate
of production ,outflow and exchanges with
anterior segment.

07/15/2021 39
 INORGANIC IONS

 concentrations of sodium, potassium, and

magnesium are similar to plasma
 level of calcium & phos is only half that of
plasma.
 2 major anions ----chloride and bicarbonate.
 Iron, copper, and zinc same levels as in plasma, I
mg/mL.

07/15/2021 40
 ORGANIC ANIONS

 Lactate -The most abundant of organic cpds

-Resulted from glycolytic metabolism

 Ascorbic acid (vitamin C) -The most unique

constituent
-0.6 to 1.5 mmol/L
-10- 50 times higher than in plasma
-Antioxidant
- Actively transported by Na+ -dependent L-
ascorbic acid transporter

07/15/2021 41
 CARBOHYDRATES
 Glucose concentration 70% of plasma.
 Occurs by facilitated diffusion.
 Increased in diabetes

-Refractive error
-cataract
 Inositol, important for phospholipid synthesis

10 times that in plasma.

07/15/2021 42
 PLASMA AQUEOUS
VITROUS
 Na 146 163 144
 cl 109 134 114
 H2CO3 28 20 20-30
 Ascorbate 0.04 1.06 2.21
 Glucose 6 3 3.4

07/15/2021 43
 GLUTATHIONE AND UREA
 1 to 10 micmol/L and plasma 5 micmol/L

 Derived by diffusion from blood(erythrocytes) or

active-transport from lens and cornea.
-Maintains ascorbate in its functional form
-Remove excess hydrogen peroxide
-Detoxification of electrophilic compounds
-Protects from oxidative damage

07/15/2021 44
 UREA
 80% and 90% of that in plasma.
 60 kD crosses epithelial barrier quite readily.
 Effective in the hyperosmotic infusion treatment
for glaucoma.
 Mannitol is(182 kD) preferred to urea

07/15/2021 45
 PROTEINS
 Blood-aqueous barrier prevents diffusion of plasma
proteins into posterior chamber
 Enter aqueous humor through root and anterior
surface of iris.
 0.02 g /100 mL, plasma 7 g/100 mL.
 Albumin and transferrin, account for 50% of all.
 Might be synthesized by ciliary body and secreted

07/15/2021 46
 C4—immunemediated inflammation responses
 Alpha2 macroglobulin -- carrier protein and
proteinase inhibition, clearance and processing of
foreign peptides
 apolipoprotein D --transports hydrophobic
substances
 selenoprotein P --antioxidant

07/15/2021 47
PROTEINASES AND INHIBITORS
 Cathepsin D- degrades neuropeptides ,csf
 Cathepsin 0- normal cellular protein degradation
and turnover.
 Synthesized and secreted by ciliary epithelial
cells.
 Proteinase inhibitors ---alph2 macroglobulin
and a1-antitrypsin.
 Imbalance ----alteration in aqueous humor
composition, eg, glaucoma

07/15/2021 48
 ENZYMES
 Activators, proenzymes, and fibrinolytic enzymes,
-Regulates outflow resistance
 Plasminogen and plasminogen activator,
 Increased levels in certain pathologic conditions.
such as retinoblastoma
 3 enzymes appear to be catalytic
1.Hyaluronidase
2. Carbonic anhydrase
3. Lysozyme

07/15/2021 49
NEUROENDOCRINE PROTEINS
 Ciliary epithelia is similar to neuroendocrine glands
elsewhere
- Neurotensin
- Angiotensin
- Endothelins
- Natriuretic peptides
 vascular hemodynamic effects
 lOP regulation or aqueous secretion
 circadian lOP rhythms

07/15/2021 50
GROWTH-MODULATORY FACTORS

 Modulate proliferation, differentiation, functional

Viability, and wound healing of ocular tissues.
 Include
-TGF-1 and-2
- aFGF and bFGF
- IGF-I
-IGFBPs
-VEGF
- Transferrin

07/15/2021 51
 Synergistic, and sometimes opposite biological
activities.
 Results in lack of significant mitosis of corneal
endothelium and trabecular meshwork

07/15/2021 52
 Disruption in balance of growth factors
-Production of plasmoid aqueous
-Abnormal hyperplastic response of lens
epithelium and Corneal Endothelium
 Depends on
- Receptors on target tissues
- Interactive effects with extracellular
matrix and proteases.
 IGFBPs & IGF-I elevated in diabetes

07/15/2021 53
 VASCULAR ENDOTHELIAL
GROWTH FACTORS
 VEGF-A, -B, -C, -D and placental growth factor
 Regulator of angiogenesis and vascular
permeability(hypoxia )
 Three VEGF receptors
1. VEGFRI -positive and negative angiogenic effects.
2. VEGFR2 -mitogenic, angiogenic, and vascular
permeability
3. VEGFR3 -angiogenic effects on lymphatic vessels

07/15/2021 54
 VEGF-A levels are increased
-Proliferative diabetic retinopathy
-Occlusion of central retinal vein
-Iris neovascularization

07/15/2021 55
OXYGEN AND CARBON DIOXIDE

 O2 partial pressure 55 mm Hg
 Derived from blood supply to Ciliary body and
iris
 Corneal endothelium, lens, trabecular critically
dependent on aqueous oxygen

 Carbon dioxide content range 40-60 mm Hg, 3%

of the total bicarbonate
 Determine ph(7.5-7.6)
 Lost thru tear film

07/15/2021 56
ANGLE OF ANTERIOR CHAMBER
 Volume of anterior chamber is 200 μL, posterior
chamber 60 μL
 Aqueous drainage
 Formed by root of iris, anterior ciliary body, scleral
spur,trabecular meshwork and Schwalbe’s line

07/15/2021 57
07/15/2021 58
ANGLE STRUCTURES
 Visible with gonioscopy
 Schwalbe line
 corneal wedge
 trabeculum
 Schlemms canal
 scleral spur
 ciliary body
 Iris processes

07/15/2021 59
THINGS TO BE LOOKED DURING
GONIOSCOPY
 Shape &contour of iris
 Degree of pigmentation & pseudo exfoliation
 Deepest structure visible
 PAS
 New blood vessels
 Angle recession

07/15/2021 60
 ANGLE GRADING
 Shaffer
 Spaeths
 Slit beam
 Diffuse beam

07/15/2021 61
SHAFFER GRADING

07/15/2021 62
07/15/2021 63
07/15/2021 64
 AQUEOUS OUTFLOW
ANATOMY
1. Trabecular meshwork(60% to 80% resistance)
 Sieve-like structure
 Collagenous connective tissue core covered by
endothelial layer.
 Its cells are phagocytic, during inflammation and after
laser treatment
 brown or muddy due to Large number of pigment
granules
 Number of trabecular cells decreases with age, and
basement membrane beneath them thickens.

07/15/2021 65
 Has three portions
Uveal meshwork
 Innermost part of trabecular meshwork
 Extends from iris root and ciliary body to
Schwalbe's line.
 Has openings 25 micm-75 micm.

07/15/2021 66
07/15/2021 67
 Corneoscleral meshwork
 Larger middle portion
 Extends from scleral spur to lateral wall of scleral
sulcus.
 Openings 5 μm-50 μm
Juxtacanalicular (endothelial) meshwork
 outermost portion
 Has layer of connective tissue lined by endothelium.
 connects corneoscleral meshwork with Schlemm’s
canal..
 Offers the normal resistance to aqueous outflow
07/15/2021 68
07/15/2021 69
 2. Schlemm’s canal
 Endothelial lined oval channel in scleral sulcus.
 Inner wall contain giant vacuoles.
 Outer wall lined by smooth flat cells and Have
openings of collector channels

07/15/2021 70
 3. Collector channels(Intrascleral aqueous vessels)
 25-35 in number
 Leave Schlemm’s canal to terminate into
episcleral veins.
 Intrascleral aqueous vessels
-Larger vessels (aqueous veins)
-Smaller collector channels

07/15/2021 71
07/15/2021 72
07/15/2021 73
07/15/2021 74
AQUEOUS OUT FLOW TRACT
 continuously formed and drained.
 Trabcular mesh work - Schlemms canal -
collector channells - episcleral vv - anterior
ciliary vv - vortex vv- cavernous sinus
 Pressure dependent

07/15/2021 75
07/15/2021 76
 Mechanism of aqueous transport across inner
wall of Schlemm’s canal
Vacuolation theory
 Transcellular spaces in endothelial cells forming
inner wall of Schlemm's canal.
 open as vacuoles and pores in response to
pressure
 pressure gradient (10 mm of Hg) is responsible
for unidirectional flow of aqueous

07/15/2021 77
07/15/2021 78
REGULATED BY CILIARY MUSCLE
 Muscle tendons inserted to trabecular meshwork.
 Tendons of muscle bundles join with elastic fibers of
scleral spur. 
 Insert into Schwalbe's line
 Connected with fibrils to schlemms canal

Contraction/accomodation

Trabecular lamellae separated

Scleral spur pulled posteriorly and internally
Schlemm's canal dilated
07/15/2021 79
 STEROIDS
 Dexamethasone reduces phagocytic and
extracellular protease activity
  Modulation of macromolecular metabolism or
prostaglandin/adrenergic interaction

07/15/2021 80
 Posterior chamber and into vitreous, most of the anterior chamber
via pupil
 Ant/post /pup iris-lens synechae,intumucsent cataract

Ciliary block,tumours, retrolental fibroplasia

Pupillary block

Antiglaucoma drugs with miotics

peripheral iridotomy/iridectomy
07/15/2021 81
UVEOSCLERAL OUTFLOW

 pressure-independent outflow, affected by age

 Constant 0.5 μL/minute in 10 to 40 mmHg
 Into supraciliary and suprachoroidal spaces.
 Increased by cycloplegia, adrenergic agents,
prostaglandin analogs, and cyclodialysis
 Decreased by miotics

07/15/2021 82
 Pilocarpine causes contraction of ciliary muscle,
squeezing spaces between ciliary muscle
bundles, reducing access of aqueous to this
pathway.
 Atropine opens access to this pathway.
 Vice versa to trabecular mesh work
 60% increase outflow after single submaximal
dose of prostaglandin F2α
 multiple submaximal doses >100% increase.

07/15/2021 83
 MECHANISM
 Relaxation of ciliary muscle
 Subsequent dissolution of type I and type III
collagen between muscle bundles.
 prostaglandins are released during inflamation
- Remove debris,proteins from tmw,choroid
-Redirection of aqueous outflow from trabecular
to uveoscleral pathway(4x)

 B-adrenergic agonists --increase us out flow

- Relaxing effect
-prostaglandin synthesis
07/15/2021 84
07/15/2021 85
 REFERENCES
 BCSC-SECTION 2&10
 DUANES
 COMPREHENSIVE OPHTHALMOLOGY
 KANSKI

07/15/2021 86
THAN
K YO U

07/15/2021 87