Day 10 (1): Glaucoma Anatomy, IOP and Aqueous Humor Dynamics Flashcards
What is the limbus?
- transition ZONE between the cornea and the sclera
Parts:
1. Scleral Sulcus
- indentation on the inner surface of the limbus
+ Schlemm’s canal: once enclosed by the TM
+ Intrascleral channels: drainage of the canal to venous circulation
+ Episcleral veins: venous drainage of the Schlemm’s canal
2. Scleral Spur
- sharp posterior margin of the sulcus
3. Trabecular Meshwork
- sieve-like structure bridging the sulcus & converting it to a tube
- attached on the scleral spur and the peripheral posterior cornea
4. Schwalbe’s Line
- ridge formed by the insertion of the TM on the peripheral posterior cornea
What is the main route of aqueous outflow?
Anterior chamber –> Trabecular meshwork –> Schlemm’s canal –> Intrascleral channels –> Episcleral veins –> Ophthalmic veins
What are the different zones in the iridocorneal angle seen in gonioscopy?
Anterior (Central) to Posterior (Peripheral)
1. Schwalbe’s Line: WHITE
2. Non-pigmented Trabecular Meshwork: WHITE
3. Pigmented Trabecular Meshwork: BROWN
4. Scleral Spur: WHITE
5. Ciliary body band: BROWN
6. Iris root: BROWN
What is the ciliary body?
- 6 - 7 mm right-triangular body bridging the anterior and posterior segments of the eye
- part of the anterior uveal tract (together with iris)
- SITE of aqueous humor production
- adult AP length:
+ nasally: 4.5 to 5.5 mm
+ temporally: 5.5 to 6.5 mm
+ 2 years old: 3/4 of adult dimension
Zones:
A. Pars Plicata (Corona ciliaris)
- inner, anterior zone ~ 25% of CB length
- thicker, vascular and ciliated portion
- function: lens accommodation and uveoscleral outflow
- Apex
- pointed POSTERIORLY towards the ora serrata and posterior chamber - Base
- continuous with the iris and the choroid
- attached to the sclera near the SCLERAL SPUR via longitudinal muscle fibers - Iridocorneal Angle/Anterior Chamber Angle
- angle formed by the peripheral cornea and the iris root on the anterior aspect of the CB - Ciliary Body Band
- band of ciliary body peeking between the root of the iris and the scleral spur - Ciliary Processes
- finger-like projections that attach to the lens zonules
B. Pars Plana (Orbicularis ciliaris)
- outer, posterior zone ~ 75% of CB length
- flatter and less vascular portion
- joins the choroid at the ORA SERRATA
C. Supraciliary Space/Lamina Fusca
- potential space between the CB base and the sclera
- continuous with the suprachoroidal space
Discuss the embryology of the ciliary body.
4-mm
- (+) optic vesicle: developing from the forebrain
- (+) optic stalk: connects the eye to the brain
7.5-mm:
- (+) bilayered optic cup: formed by invagination of vesicle upon itself
- (+) lens vesicle: formed from the lens placode superficial to the optic vesicle
Eye development is intimately related with IOP control
- IOP is an impetus to eye development by generating the force that stimulates the formation of ciliary folds and changes in the shape and curvature of the cornea
- should be constant and at a steady state:
AH production (inflow rate) = AH drainage (outflow rate)
- AH production: 4 - 6 months AOG
What are the basic types of genes that regulate eye development?
- Structural genes
- example: cytoskeletal components (collagen, hyaluronate)
- function: encode molecules with general biochemical and structural functions - Regulatory genes
- examples: transcription factors, signaling molecules
- function: control expression of specialized gene - Cell-specific genes
- function: encode specialized proteins and molecules for a particular cell type with very specific functions
What are the layers of the ciliary body?
- Supraciliary Space/Lamina fusca
- most external layer and adjacent to the sclera
- continuous with the SUPRACHOROIDAL SPACE - Muscle layer: functions as a unit but with 3 distinct layers
- LONGITUDINAL: outermost; attaches the CB to the scleral spur and extends to the equator
- RADIAL: oblique midportion
- CIRCULAR: girdle-like innermost part; contraction causes relaxation of zonules and lens accommodation - Vascular layer: synonymous to stroma
- connected to the Ciliary arteries
- where most antibody-producing PLASMA CELLS are located - Lamina Vitrea
- anchors epithelium to underlying layers to withstand traction by lens zonules
- continuous with BRUCH’S MEMBRANE - Epithelium: bilayer with fusion of apices by tight junctions
A. Outer Pigmented Layer
- continuous with RPE
- uniformly cuboidal all throughout
B. Inner NON-Pigmented Layer
- between aqueous and outer pigmented epithelium
- continuous with NSR
- pigmented anteriorly and becomes the PIGMENTED Posterior Epithelium of the Iris
- columnar in the pars plana and gradually shortens to cuboidal towards the iris
- site of aqueous humor production
- BLOOD-AQUEOUS BARRIER: tight junctions/zonula occludens between epithelial cells
- Internal Limiting Membrane
- continuous with ILM of retina
- basement membrane that separates the epithelium from the aqueous humor
Discuss the different muscles in the ciliary body.
Muscle layer:
- functions as a unit but with 3 distinct parts
- ONLY innervated by the PARASYMPATHETIC system
- baseline: relaxed state with radial tension on the zonules
- LONGITUDINAL
- outermost
- attaches the CB to the limbus at the scleral spur
- extends to the equator - RADIAL
- oblique midportion
- less distinct than other layers - CIRCULAR
- girdle-like innermost portion
- runs parallel to the limbus
- contraction causes relaxation of zonules and lens accommodation
Discuss the vascular supply of the ciliary body.
Summary:
Iris and Pars Plicata: Major Arterial Circle (ACA + Long PCA)
Ciliary Body (Pars Plana): Long PCA
A. Major Arterial Circle of the Iris
- immediate vascular supply of the IRIS and ciliary processes of the PARS PLICATA
- formed by the anastomosis of the branches of LPCA and ACA
- found in the CB near the iris root WITHIN the CB muscles
B. Anterior Ciliary Arteries (7)
- may arise from terminal branches of the ophthalmic artery or from muscular arteries
- located on the surface of the sclera
- RECTI muscles: 2 branches for each except LR (1 only)
- other branches:
1. Episcleral: episcleral plexus and form an EPISCLERAL circle
2. Scleral: sclera
3. Limbal: limbus
4. Conjunctival: conjunctiva
C. LONG Posterior Ciliary Arteries (2: 1 nasal, 1 temporal)
- enters the eye in the nasal and temporal aspects
- courses along the suprachoroidal and supraciliary space
- branches:
1. anastomose with branches from ACA: Major Arterial Circle of Iris
2. loops back: Recurrent Ciliary Artery to the anterior choroid
What are the ciliary processes of the Pars Plicata?
- functional unit responsible for aqueous humor secretion
Layers:
- Vascular Layer
+ Capillaries: center of each process
+ Capillary endothelium: (+) pseudo-porous areas of fused plasma membranes and absent cytoplasm which serve as sites of sites of increased permeability
+ Stroma: intervening connective tissue and extracellular matrix separating the ciliary capillaries from the epithelium - Lamina vitrea
- anchors epithelium to stroma to withstand traction by zonules
- continuous with BRUCH’S MEMBRANE - Epithelium: bilayer with fusion of apices by tight junctions
A. Outer Pigmented Layer
- continuous with RPE: (+) melanin granules
- BM on the stromal side and apex fused with inner epithelium
- uniformly cuboidal all throughout
B. Inner NON-Pigmented Layer
- between aqueous and outer pigmented epithelium
- continuous with NSR
- pigmented anteriorly and becomes the PIGMENTED Posterior Epithelium of the Iris
- columnar in the pars plana and gradually shortens to cuboidal towards the iris
- actual site of aqueous humor production
- BLOOD-AQUEOUS BARRIER: tight junctions/zonula occludens between epithelial cells
- Internal Limiting Membrane
- continuous with ILM of retina
- basement membrane of the INNER NON-pigmented epithelium that separates the epithelium from the aqueous humor
Discuss the intercellular connections between the epithelial layers of the ciliary body.
- Gap Junctions
- for cellular communication
- found between P-P cells, NP-NP cells and P-NP cells - Tight Junctions/Zonula Occludens
- ONLY between NP-NP cells
- forms the Blood-Aqueous Barrier:
+ barrier only to intermediate and high-MW substances like proteins
+ leaky VS BRB which is non-permeable
+ still allows diffusion of IONS and WATER
Discuss the autonomic innervation of the ciliary body.
SYMPATHETIC: Superior Cervical Ganglion
- innervate ciliary vessels, muscles & epithelium
- neurotransmitters: Catecholamines
- remember: BETA INCREASE, ALPHA DECREASE (BIAD)
- Ciliary vessels
- receptor: Alpha-1
- effect: vessel constriction –> DECREASED AH PRODUCTION - Ciliary epithelium
- Alpha-2: DECREASED AH SECRETION
- Beta-2, CA receptors: INCREASED AH SECRETION
- Beta-2: most prevalent adrenergic receptor - Ciliary muscles
- receptor: Alpha-2
- effect: muscle relaxation –> INCREASED AH OUTFLOW via the uveoscleral pathway
PARASYMPATHETIC: Edinger-Westphal Nucleus
- innervate ciliary muscles
- neurotransmitter: Acetylcholine
- receptor: Muscarinic
- effect: muscle contraction
1. Zonular relaxation –> lens accommodation and forward displacement
2. Pupil constriction –> widening of the iridocorneal angle –> increased AH outflow via the trabecular meshwork
What is the Aqueous Humor?
- derived from plasma within the capillary network of the ciliary processes
- convection current:
+ responsible for the flow of aqueous humor
+ due to a temperature gradient between the posterior chamber (warm) and the anterior chamber near the cornea (cooler)
+ cornea: dissipates heat into the air interface
Pathway:
1. Ciliary processes
2. Posterior chamber
3. Pupil
4. Anterior chamber
5. Outflow: conventional or uveoscleral
What are the functions of the aqueous humor?
- IOP maintenance
- important for ocular development and globe integrity - Delivery of nutrients and substrates + Drainage of metabolites and wastes from structures of the anterior segment
- High concentrations of ascorbate to counter oxidative damage
- Local paracrine signaling and immune responses
- Part of the eye’s optical pathway system
What is the composition of the aqueous humor?
Characteristics:
1. slightly HYPERtonic
2. slightly acidic (pH 7.2)
3. VERY HIGH (20x) ascorbate: protects against UV-induced oxidative damage
4. HIGH lactate: glycolytic byproduct of lens, cornea, etc.
5. HIGH chloride
6. VERY LOW (200x) protein than plasma
Note: Flare
- sign of inflammation and breakdown of the BAB
- > 20 mg protein/100 mL solution
- Tyndall effect: scattering of light by small suspended particles floating in a medium
What is the Blood Aqueous Barrier?
Components:
1. Tight junctions between the INNER non-pigmented epithelial cells of the ciliary body
- barrier to passage of intermediate and high-MW substances
2. Endothelium of the INNER wall of the Schlemm’s canal
- prevents backflow of aqueous into the anterior chamber
Causes of BAB breakdown:
1. Infection and inflammation
2. Drug-induced
3. Trauma
Effects of BAB breakdown:
1. Pseudofacility
- entry of plasma components into the aqueous humor
- higher intraocular oncotic pressure PROMOTE fluid movement INTO the eye
2. Hypotony
- usually seen in inflammatory processes
- causes:
+ TRANSIENT reduction in AH secretion due to interference with active transport mechanisms
+ PROSTAGLANDIN increases uveoscleral outflow
What 3 transport mechanisms are involved in AH production?
- Diffusion: usually LIPID-soluble substances
- passive movement DOWN a gradient
- CHARGE- or CONCENTRATION-based gradient - Ultrafiltration: usually WATER-soluble substances and water
- passive movement DOWN a gradient
- PRESSURE-based gradient
- balance between hydrostatic and oncotic pressure in the capillaries
- HYDROSTATIC pressure: intravascular > intraocular
+ due to blood flow
+ FAVORS fluid movement into the eye
- ONCOTIC pressure: intravascular > intraocular
+ due to protein concentration
+ RESISTS fluid movement into eye - Active secretion: PROTEINS or large molecules
- energy-requiring movement AGAINST a gradient
What are the steps in aqueous humor production?
*Plasma: within the ciliary capillaries
- ULTRAFILTRATION
- across the capillary walls promoted by increased hydrostatic pressure in the vessels
*Ultrafiltrate: within the stroma
- DIFFUSION
- in the stroma and between OPE cells - MODIFICATION
- composition in the intercellular clefts between the INPE cells by active secretion or passive diffusion of solutes - ACCUMULATION
- solutes accumulate behind the tight junctions between INPE cells creating sufficient osmotic force to attract water - ACTIVE SECRETION
- solutes cross the tight junctions into the posterior chamber - OSMOTIC FLOW
- concentration gradient of solutes across compartments promote flow of water into the posterior chamber
*Aqueous Humor: within the posterior chamber
How does carbonic anhydrase affect aqueous humor production?
Carbonic Anhydrase
- found within the INPE cells
- facilitates interconversion between carbon dioxide and bicarbonate ion
Bicarbonate ion
- functions as a pH regulator essential for the proper functioning of the Na-K-ATPase pump
Na-K-ATPase pump
- transports 3 Na ions OUT of the cell in exchange for 2 K ions INTO the cell AGAINST their concentration gradients
- provides the driving force for the the osmotic flow of water into the posterior chamber as the AQUEOUS HUMOR
What is the rate of aqueous humor production and turnover?
Production: 2 - 3 uL/min (awake); 1 - 1.5 uL/min (asleep)
Turnover: 1.0 - 1.5% of the anterior chamber volume/min
Measurement: Fluorophotometry
- instillation of topical fluorescein and the optical measurement of its gradual dilution and change in concentration in the anterior chamber over time
What factors affect the rate of aqueous humor production?
- Circadian rhythm
- rates in sleep state (night) ~ 1/2 of rates when awake (day)
- due to DECREASED epinephrine: acts on the BETA-2 receptors to promote AH SECRETION - Aging
- DECLINE in production by 2 - 3% per decade after 10 yo - Sexual variation
- AH flow in MEN > women
- differences in size of ocular structures - Disease states
- trauma, inflammation, infection
- affects the integrity of the BAB - Drug-induced
- general anesthetics
- systemic hypotensives: decrease ciliary vessel blood flow and hydrostatic pressure
- ocular hypotensives: exert neurohumoral regulation of ciliary vessels and epithelium
