Aqueous Outflow and Regulation (M2) Flashcards
Where does the trabecular meshwork begin?
Schwalbe’s line (end of Descemet’s)
What is at the posterior end of the trabecular meshwork?
bordered by scleral spur and infiltrated by ciliary muscle tendons
What are the layers of the trabecular meshwork?
- Uveal
- Corneoscleral
- Juxtacanalicular
What is the small, roundish branching trabeculae (~4μm diameter)?
uveal meshwork
How may layers thick is the uveal meshwork? 1. Corneoscleral meshwork? 2.
- 1-3
2. 8-15
Are the spaces in the corneoscleral meshwork larger or smaller than the uveal meshwork? 1. What is their shape? 2
- smaller
2. elliptical
What comprises of loose connective tissue with 2–5 layers of scattered cells that are embedded in a loosely arranged fibrillar extracellular matrix?
juxtacanalicular tissue
Does the juxtacanalicular tissue form the trabecular lamellae?
no
What is adjacent to juxtacanalicular tissue?
endothelial cells lining inner Schlemm’s canal
How is the juxtacanalicular tissue basement membrane arranged?
discontinuous
What are the uveal and corneal scleral lamellae lined with?
endothelial cells
What is the uveal meshwork continuous with?
corneal endothelium
What regulates the outflow for the trabecular meshwork?
mechanosensation of TM cells and elasticity of the ECM
How is mechanosensation of TM cells accomplished?
transmembrane integrin proteins
What is found between the first corneascleral lamellae and the subepithelial cells of the JCT?
elastic complex
What contributes to the elasticity of the trabecular meshwork?
- Fibrillar and non-fibrillar collagen
- Elastin
- Matricellular proteins
- GAGs/proteoglycans
- Proteins involved in proteoglycan turnover
What is the matricellular protein found in the trabecular meshwork?
Myocillin
What are the nerves that are found in the trabecular meshwork?
- afferent mechanoreceptors in scleral spur
2. para and sym
What is the circular structure that provides drainage for the aqueous humor and delivers it to venous return?
Schlemm’s canal
What is the mechanism of trabecular meshwork drainage into Schlemm’s canal?
Formation of giant vacuoles
Are there more intracellular pores in Schlemm’s canal or paracellular pores?
3-4 x more intracellular than paracellular pores
What causes a decrease in the number of pores in Schlemm’s canal?
POAG (primary open angle glaucoma)
What cells can get through the trabecular meshwork by deforming and changing shape?
RBCs and WBCs
What is an alternate to TM for entry into Schlemm’s canal?
Valve-like protrusions found emanating from inner wall of Schlemm’s canal (exit at distal end)
How long does fluid movement into circulation take for uveoscleral AH outflow? 1. What is the rate of this outflow? 2
- about 2 hours
2. ~0.3 – 1.5 μl/minute
What type of outflow is independent of IOP (unless significant drop)?
uveosceral outflow
What is the driving force for the uveoscleral outflow?
pressure between the anterior chamber and the suprachoroidal space
Which type of ciliary muscle fibers run along inside of sclera?
longitudinal fibers
Which type of ciliary muscle fibers fan out from chamber angle toward ciliary processes?
radial fibers
Which type of ciliary muscle fibers run parallel to schlemm’s canal?
circular fibers
What happens to uveoscleral outflow when ciliary muscles contract?
reduced
What happens to trebecular meshwork outflow when ciliary muscles contract?
increased
What are the major contributors to resistance of AH through the trabecular meshwork?
JCT and surrounding ECM
What is the mechanism of Laser trabeculoplasty?
Ablates TM tissue to allow less resistance and greater outflow to reduce IOP
What is Peripheral Iridotomy typically used for? 1. What does it do? 2
- narrow angle glaucoma
2. Allows fluid to drain more directly to TM with a narrow angle
What is a Muscarinic agonist that stimulates ciliary muscle, which pulls on trabecular meshwork and decreases resistance (increases facility)?
pilocarpine
What is the mechanism of Echothiophate?
acetylcholinesterase inhibitor causing indirect stimulation of muscarinic receptors
What adrenergic receptors are found in the ciliary body?
β2, α1, and α2 receptors
What adrenergic receptors are found in trabecular meshwork endothelial cells?
β2 receptors
What is the mechanism of adrenergic agonists?
increase facility of trabecular meshwork by activating cAMP cascade and reducing actin filaments forming the cytoskeleton (independent of ciliary body)
What are examples of adrenergic agonists used to treat glaucoma?
- epinephrine
- Norepinephrine
- isoproterenol
What is the mechanism of Brimonidine?
α2 agonist that relaxes ciliary smooth muscle and increases uveoslceral outflow
What is the mechanism of Apraclonidine?
α2 agonist
What drug can lower IOP by inhibiting cytoskeletal structure and relaxing cells inducing an increase in facility?
Rho-kinase inhibitor
What are Latanoprost (Xalatan), travoprost (Travatan), unoprostone (Rescula), bimatroprost (Lumigan) examples of? 1. What is their mechanism? 2
- prostaglandin analogs
- Relaxes ciliary muscles and increase uveoscleral outflow.
Also causes increase of MMP and degradation of collagen which reorganize scleral tissue and increases its permeability
What is the most common glaucoma medication used?
prostaglandins
What receptors are found in trabecular cells and cortisol induces sodium ion transport into aqueous (via NKA activation)?
glucocorticoid
What is the mechanism of glucocorticoids in relation to the filtration of AH?
decrease facility due to a build up of ECM in trabecular meshwork and rearrangement of cytoskeleton in TM cells
With advanced age, what happens to the trabecular meshwork?
- a loss of endothelial cells occurs which causes the inner uveal and corneal scleral tissue to become “glued” together
- Increased ECM
- Causes increased resistance
What ligand is increased in POAG?
TGFβ
Do pigmented cells of the iris, ciliary body, retina, and corneal endothelium assist or inhibit inflammation?
inhibit inflammation by suppressing activation of T-cells
What causes uveitic glaucoma?
clog of trabecular meshwork with immune cells, proteins, debris, or fibrin due to inflammation
What are pharm. treatments aimed to influence in the fluid mechanics of outflow equation?
aimed at reducing Fin or by increasing Ctrab and Fu
How much can a heart pulse influence IOP?
1-2 mmHg
How does laying down or head below level of heart impact IOP?
increases IOP
How does eyelid closure impact IOP?
increases IOP
How does eyelid opening impact IOP?
increases IOP
What are the etiologies of primary closed angle glaucoma?
- hyperopia
- old age
- women
What is the process in which dendritic cells avoid immune effectors in ocular tissues (T-cells) that would otherwise stimulate immunogenic inflammation called?
Anterior Chamber Associated Immune Deviation (ACAID)