Flashcards in Exam 1 Koh- Aqueous Humor 2 Deck (61):
What are the 3 outflow systems of the AH?
Corneoscleral meshwork, uveoscleral meshwork and episcleral vessels
What is the conventional outflow of the AH?
(65-90%) trabecular meshwork, Schlemm canal, collector vessels, intrascleral plexus, episcleral venous system
What is the uveoscleral outflow of the AH?
(Pressure insensitive) Pass across the face of ciliary muscle, into suprachoroid, and through scleral coat to end in the vortex system
What is the trabecular meshwork?
A specialized tissue at the chamber angle, is the major site for regulation of the normal bulk flow of the aqueous humor; superficial uveal meshwork, the deeper corneoscleral meshwork, and the juxtacanalicular connective tissue (JCT) adjacent to Schlemm's canal
How does the trabecular meshwork function?
Self-cleaning, unidirectional, pressure-sensitive, low- flow (2 micoliters/min/mmHg) biologic filter for the AH, and contributes thereby to control of the IOP
What is the trabecular meshwork outflow pathway?
Trabecular meshwork, Schlemm's canal, and the collector channels/aqueous veins
What is Schlemm's canal?
The inner wall endothelium, its basement membrane and the canal lumen
What are collector channels?
Collector channels and aqueous veins connect the canal lumen to the episcleral veins on the surface of the eye
How many collector channels are along the outerwall of Schlemm's canal?
What is the trabecular meshwork structure?
A lattice of connective tissue and endothelial cells embedded in GAG-like ground substance, then into the Schlemm canal and general venous circulation (episcleral vessels)
Why is there resistance in the trabecular meshwork?
In the vicinity of the inner wall endothelium of Schlemm's canal, its basement membrane, and the juxtacanalicular connective tissue
What are the tissue beams in the trabecular meshwork?
Or lamellae that have a core of collagenous and elastic fibers, and care covered by flat cells which rest on a basal lamina. The beams attach to one another in several layers and form a porous filter-like structure
What are the properties of the trabecular meshwork cells?
Have active phagocytic properties, high levels of cytoskeletal actin, lower levels of microtubules also contain vimetin and desmin = smooth muscle
Trabecular meshwork cells are specialized both for ______ transport of water and solutes and ______
Most of the matrix component in trabecular meshwork are synthesized and degraded by _______ cells
The phagocytic activity of TM cells is associated with what two things?
GAG-degrading enzymes and acid phosphatase
Each lamella or beam mostly contains what types of collagen?
1 and 3
The fine fibril contain what type of collagen?
The cells covering the trabecular meshwork beams is rich in collagen type ____ and ___
4 and laminin
The elastic fibers in collagen have a considerable amount of ____ ____ material
The spaces between the juxtaglomerular cells and extracellular maxtrix fibers contains what?
Ground substance, consisting of various proteoglycans and hyaluronan
What types of glycosaminoglycans (GAGs) are in the AH?
Hyaluronic acid, dermatan sulfate, and chondroitin sulfate
What are plaques?
Accumulation of extracellular matrix structures with age
What contributes to interstitial flow resistance?
Proteoglycans and GAGs
AH outflow resistance may be decreased by nearly 50% in bovine eyes after perfusion with _________
Secreted ECM proteins influence cell function by modulating ______ ______
What are the matrix proteins?
Elastin, fibronectin, versican, laminin, thrombospondin-1, SPARC (secreted protein, acidic and rich in cysteine), myocilin, optineurin
What 2 things are active in handling H2O2 and free radicals?
Catalase and a glutathione-dependent system
What is TGFb?
A member of a family of dimeric polypeptide growth factors
What are the isomers of IGF-b?
TGF-b1, TGF-b2, TGF-b3
What is the predominant isoform of TGFb as it is found at relatively high concentration in the AH of normal eyes?
What are the effects of TGF-b?
Signaling does not only effect ECM turnover in the TM, but also acts on the TM actin cytoskeleton
The uveoscleral pathway accounts for what percentage of outflow?
What is the resistance like in the uveoscleral outflow?
Minimal, main resistance is within the ciliary muscle
Which outflow has prostaglandin F2alpha analongs?
What is the uveoscleral flow rate?
Pev to be about 8mmHg, calculated uveoscleral outflow to be about 0.8 micoliters/min (36%)
What are the values for uveoscleral flow?
In normal eyes between 0.14 and 1.52 micoliters/min, constituting 12-54% of total aqueous outflow
Which outflow is more sensitive to pressure change?
What is episcleral venous pressure?
Aqueous humor draining via the canal of Schlemm into a network of intrascleral collector channels that drain into the scleral veins
Uveoscleral drainage is possible owing to the fact that pressure in suprachoroid is _____ mmHg lower than in the anterior chamber
The difference from the suprachoroid and the anterior chamber can be reversed after _______ and can lead to hypotony and choroidal effusions
What are glaucoma risk factors?
IOP, CCT, age, C/D ratio, VF loss, pseudoexfoliation
What is the glaucoma continuum?
Normal -> acceleration of apoptosis -> ganglion cell death/axon loss -> Retinal nerve fiber layer change (undetectable) -> Retinal nerve fiber layer change (detectable) -> short wavelength automated perimetry VF changes -> standard automated perimetry VF changes -> VF change (moderate) -> VF change (severe) -> blindness
What are features of primary open angle glaucoma?
Excessive depletion of meshwork cells, failure of phagocytosis, closure of Schlemm canal, progressive narrowing of the lumina of collector channels
What happens to the trabecular meshwork in primary open angle glaucoma?
Thickening and fusion of trabeculae, alterations in meshwork myocillin, accumulation of ECMs, GAGs, glycoproteins and small proteins in the JCT
What are 3 glucocorticoids used in the AH?
Dexamethasone, actin, and MMPs
What does dexamethasone do?
Increased deposition of extracellular matrix material in the outflow pathway, increased expression of myocilin
What does actin do?
Cause the formation of cross-linked actin networks in cultured HTM cells, less pliable and more likely to inhibit outflow
What do MMPs do?
Downregualtes matrix-metalloproteases (MMP2,3, and 14), less ECM turnover and less outflow, MMP3 to help degrade and remodel ECM
What are glucocorticoid effects on the trabecular meshwork?
TM cells have GC receptors and targets of GC activtiy, GCs alter the expression of hundreds of TM cells, genes, and proteins; GCs alter TM cell functions (decrease proliferation and phagocytosis), GCs increase extracellular matrix deposition, GC reorganize the actin cytoskeleton, GCs alter cellular junctions
What are the autonomic regulation steps for secretion of AH?
Ciliary body to posterior chamber: 1) uptake of solute and water at stromal surface by PE, 2) transfer from PE to NPE cells through gap junctions 3) transfer of solute and water by NPE cells into PC
Adrenergic receptors regulate IOP via ____ ____
What suppresses aqueous flow?
Beta blocker and alpha adrenergic agonists
Muscarinic receptors are linked to what?
PIP2 2nd messenger system (CB)
What 2 medications have good nocturnal efficacy?
Carbonic anhydrase inhibitor, prostaglandins (good but less than daytime)
What 2 medications cause a decrease in episcleral venous pressure?
Alpha-2- agonists and prostaglandins
What 3 medications increase uveoscleral outflow?
Adrenergic agents, alpha-2-agonists, prostaglandins
What medication decreases uveoscleral outflow?
What 2 medications increase conventional out flow facility?
Miotics and prostaglandins
What 3 medications decrease aqueous humor flow?
alpha-2-agonists, beta-adreno-ceptor antagonists, carbonic anhydrase inhibitors