Limbus and aqueous outflow pathways Flashcards
In addition to being the border zone beteen the cornea and sclera, what are 4 functions of the limbus?
- nourishment of the peripheral cornea
- corneal wound healing
- immunosurveillance of the ocular surface and hypersensitivity responses
- contains the pathways of aqueous humour outflow and is thus involved in the control of intraocular pressure
What may surgical incisions be made at the limbus to access?
the anterior chamber for cataract and glaucoma surgery
What is the width of the limbus?
1.5-2.0 mm
What 2 structures are produced by the change in radius of curvature between the sclera and cornea?
- external scleral sulcus
- internal scleral sulcus
What anatomical feature serves to deepen the internal scleral sulcus?
the scleral spur

What 2 key structures are housed by the internal scleral sulcus?
- canal of Schlemm
- trabecular meshwork

What structures attach to the posterior aspect of the scleral spur?
longitudinal ciliary muscle fibres

What structures does the anterior scleral spur give rise to?
corneoscleral trabeculae

What are the 6 important transitions at the limbus?
- corneal lamellae regular –> scleral random array
- stratified squamous non-keratinised corneal epithelium –> conjunctival epithelium
- conjunctival epihtleium contains goblet cells and MHC class II+ CD11c+ dendritic (Langerhans) cells
- Loops (arcades) of conjunctival and lymphatic capillaries terminate at limbus
- Descemet’s membrae and Bowman’s layer of cornea terminate in this region
- loose conjunctival substantia propria tapers off at the limbus
What is the transition of the regularly arranged coreal lamellae at the limbus?
give way to random array of lamellae in the sclear
What is the shape of the corneal termination (where it becomes the sclera)?
V-shaped

What is the change in epithelium at the limbus?
the stratified squamous non-keratinised corneal epithelium with its parallel internal and external surfaces gives way to conjunctival epithelium, characterised by a folded basal suface and interdigitating subepithelial connective tissue (sometimes forming distinct papillae)
What are the characteristics of conjunctival epithelium?
folded basal suface and interdigitating subepithelial connective tissue (sometimes forming distinct papillae)
What are 2 types of cells present in the conjunctival epithelium not present in the corneal epithelium?
- Goblet cells
- Rich network of MHC class II+ CD11c+ dendritic (Langerhans) cells
What is the change in capillaries at the limbus?
loops (or arcades) of conjunctival apillaries and lymphatic capillaries terminate at the limbus
What are the conjunctival capillaries derived from?
anterior ciliary arteries
Why are the smaller capillaries in the conjunctiva particularly susceptible to the effects of vasoactive amines?
they are not under neuronal control
What are 3 examples of vasoactive amines that small conjunctival vessels are particularly susceptibe to, that are released by local immune cells?
- histamine
- leukotrienes
- prostaglandins
What are the features of the connective tissue of the conjunctiva that tapers off at the limbus and is absent in the cornea?
- loose subepithelial vascularised connective tissue aka substantia propria
- contains immunocompetent cell types (mast cells, plasma cells, lymphocytes)
What are 3 types of immunocompetent cell types that are present in the conjunctival subepithelial vascularised connective tissue?
- plasma cells
- lymphocytes
- mast cells
What is Dua’s layer?
recently described layer anterior to Desçemet’s membrane in the cornea
represents condnsation of stromal collagen fibres

How can Dua’s layer be identified?
by dissection of the cornea using a bubble of air during preparation of the cornea for corneal transplantation
What does Dua’s layer consist of?
condensation of the stromal collagen fibres
What is the anatomical (histological) definition of the limbus?
defined by a line that follows a V shaped transition of corneal lamellae to scleral lamellae
How do pathologists define the limbus?
block of tissue bordered anteriorly by a line passing through the termination of Schwalbe’s line and the junction of the conjunctival and corneal epithleium (corneolimbal junction) and posteriorly by a line from the scleral spur perpendicular to the tangent of the external surface
What is the surgical definition of the limbus?
surgeons cut close to the blue-grey transition zone seen on external examination and incisions made here will pass anterior to the trabecular meshwork and Schlemm’s canal

Where is the trabecular meshwork?
in the chamber or iridocorneal angle, partially nestled in the internal scleral sulcus
What is the trabecular meshwork?
complex wedge-shaped circumferential band of specialised, sponge-like, connective tissue
Where is the canal of Schlemm in relation to the trabecular meshwork?
the canal of Schlemm is on the otuer aspect of the trabecular meshwork

What forms the base on which the trabecular meshwork sits?
- formed posteriorly by the scleral spur, anterior face of the ciliary muscle and the iris root

What is another name for the canal of Schlemm?
sinus venosus sclerae
Where does the apex of the trabecular meshwork terminate?
anteriorly, at Schwalbe’s line and the adjacent inntermost corneal lamellae

What are 3 anatomical zones into which the trabecular meshwork can be divided into?
- innermost uveal meshwork with cord-like trabeculae
- corneoscleral meshwork with flattened sheet-like trabeculae
- outermost cribriform meshwork beneath the inner wall of Schlemm’s canal

What are the trabeculae like in the innermost uveal meshwork?
cord-like
What are the trabeculae like in the middle corneoscleral meshwork?
flattened sheet-like trabeculae
What is the arrangement of the cribriform trabecular meshwork?
not arranged in lamellae but consists of trabecular cells enmeshed in a loose extracellular matrix of collagen (types I, III and IV), elastic-like fibres and proteoglycans
What are 4 components to the cribriform meshwork?
- trabecular cells
- loose ECM of collagen (type I, III and IV)
- elastic-like fibres
- proteoglycans
What are the 3 types of collagen found in the cribriform meshwork of the trabecular meshwork?
I, III, IV
Which trabecular layer is thought to be the main site of resistance to aqueous outflow?
cribriform meshwork
What are the elastic cores of the trabeculae continuous with?
contoinuous with the elastic fibres in the cribriform meshwork, which are connected to the inner wall of Schlemm’s canal via ‘connecting fibres’
What terminates in the elastic cores of the trabeculae?
the anterior ciliary muscle fibres
What happens to the trabecular meshwrok when the ciliary muscle contracts?
as the ciliary muscle contracts and moves inwards, the three-dmensional trabecular meshwork can be exapnded, which results in an increase in the amount of ‘free’ spaces in the ribirform meshwork
this allows greater aqueous outflow
How is aqueous outflow affected when the ciliary muscle contracts and why?
when ciliary muscle contracts, there is greater aqueous outflow
this is because the ciliary muscle contracts nad moves inwards causing the 3D trabecular meshwork to expand and increase the amount of free spaces in the cribriform meshwork
Where does aqueous humour travel through the trabecular meshwork?
travels from the anterior chamber through the intertrabecular and intratrabecular spaces, which are lined by trabecular cells
What lines the intertrabecular and intratrabecular spaces that aqueous travels through from the anterior chamber?
trabecular cells
How do the trabecular cells lining the inter and intratrabecular spaces relate to the trabeculae?
the cells envelop the trabeculae and maintain the state of hydration of the connective tissue core in a similar manner to the corneal endothelium
What are 2 functions of the trabecular cells which line the intertrabecular and intratrabecular spaces?
- hydrate the connective tissue core of the trabecular meshwork
- are phagocytic + trap and remove debris from aqueous humour as it percolates through the tortuous intertrabecular and intratrabecular spaces
What happens to the size of the inter and intratrabecular spaces as they approach Schlemm’s canal?
become narrower
What is Schlemm’s canal?
endothelium-lined 36mm long circumferential channel filled with aqueouus humour
What lines Schlemm’s canal?
endothelium
How long is Schlemm’s canal?
36mm
What is the dimension of Schlemm’s canal in the anterior-posterior axis?
200 - 400 µm
What is the depth of Schlemm’s canal?
no more than 50-60µm deep
What is the patency of Schlemm’s canal often like?
often septate
What structures drain Schlemm’s canal?
25-35 collector channels and between 2-8 aqueous veins (of Ascher)
What is the diameter of the collector channels that drain the canal of Schlemm?
20-90µm
What is the diameter of the aqueous veins that drain the canal of Schlemm?
up to 100µm in diameter
What happens to the aqueous after being drained into collector channels and aqueous veins from the canal of Schlemm?
join deep, intrascleral and episcleral venous plexuses which drain into conjunctival veins or, in the case of aquoeus vieins, may drain directly into superficial conjunctival veins
What proportion of aqueous humour drains from the anterior chamber via the trabecular meshwork and Schlemm’s canal?
70-90%
What is meant by the conventional aqueous outflow pathways?
drainage via the trabecular meshwork and the canal of Schlemm
What features characterise the inner walls of the canal of Schlemm?
transcellular channels or giant vacuoles
Where do the intracellular vacuoules on the inner wall of the canal of Schlemm have openings to, and what does evidence suggest is their function?
openings on both trabecular and luminal aspects
evidence suggests they function to drain great bulk of aquoeus humour
What causes the number and size of vacuoles lining the inner wall of the canal of Schlemm and their openings or pores to vary?
vary in a pressure-sensitive manner
In addition to aqueous draining via the vacuoles lining the inner walls of the canal of Schlemm, where else may aqueous also drain?
small quantities of aqueous may pass between endothleial cells in the canal wall
What is a genetic similarity and 2 genetic differences between the canal of Schlemm/aqueous veins’ endothelial lining and lymphatic endothelium?
- similarity: prospero homeobox protein 1 (Prox 1) present in both (is master control gene for lymphatic development)
- difference: lack of lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expression in canal of Schlemm
- difference: supporting cells in canal of Schlemm wall may have contractile properties
What is the definition of glaucoma?
progressive optic nerve neuropathy
What are 2 important risk factors for most forms of glaucoma
- raised intraocular pressure
- ageing
How does glaucoma relate to aqueous outflow pathways?
in many forms of glaucoma, pathological changes in the trabeular meshwork and Schlemm’s canal may be responsible for increased rseistance to aqueous outflow and raised, or diurnal fluctuations in, IOP
What is the pathology behind congenital glaucoma?
there is malformation of the complex 3D arrangement of the trabeculae and excess extracellular matrix in the otuer meshwork
What pathological change happens in closed-angle glaucoma?
physical blockage of the inner surface of the chamber angle by the iris
may be a primary or secondary process
What pathological change happens in open-angle glaucoma?
various forms of obstruction in the trabecular meshwork
cause of the primary form of this condition is unkonwn but there is evidence to indicate that excessive deposition of extracellular elements may occur in the cribriform meshwork
What may secondary forms of open-angle glaucoma be the result of?
debris such as lens proteins, melanin, macrophages and haemorrhagic products physically obstructing the intertrabecular and intratrabecular spaces, causing raised IOP
What proportion of aqueous humour drains via non-conventional aqueous outflow pathways?
10-30%
Is the non-conventional aqueous outflow pathway pressure sensitive?
no
What is the route of the non-conventional aqueous outflow pathways?
the intercellular spaces between ciliary muscle fibres and the loose connective tissue of the suprachoroidal space
from here, aqueous traverses the sclera via the connective tissue sheaths of nerves and vessels that pierce its substance

Where has recent evidence suggested there is exchange of aqueous, more so than previously known? (in addition to the other non-conventional outflow pathways)
exchange of aquoeus with the iris stroma and thus the iris vasuclature
Where does the term uvea come from?
Latin, uva = grape
What 3 things does the uvea, the middle vascular pigmented layer of the eye, consist of?
ciliary body, iris, choroid
How do the iris, ciliary body and choroid relate to one another?
continuous with each other and have an anterior opening, the pupil, and posteriorly the choroid is deficient at the optic nerve canal
What is the uveal tract analogous to in the brain and optic nerve?
the vascular pia-arachnoid
Where does the uveal tract anastomose with the pia-arachnoid?
optic nerve head
What type of cells line Schlemm’s canal?
single layer of non-fenestrated endothelium joined by tight junctions