Ординатура / Офтальмология / Английские материалы / Shields Textbook of Glaucoma, 6th edition_Allingham, Damji, Freedman_2010

turnover of these glycoproteins may play an important role in resistance to flow within the unconventional pathways and in mediating the action of certain pharmacologic agents (99). This is discussed further in the following section on molecular mechanisms of outflow resistance and in Chapter 28 on prostaglandins.

Uveovortex Outflow

Tracer studies in primates have also demonstrated unidirectional flow into the lumen of iris vessel by vesicular transport, which is not energy dependent (100). The tracer can penetrate vessels of the iris, ciliary muscle, and anterior choroid to eventually reach the vortex veins; however, the role of net fluid movement into the iris vasculature is probably clinically insignificant (101). Some evidence suggests that there is a process of net osmotic resorption of some aqueous humor into the uveal venous circulation, driven by the high protein content in the blood in these vessels (102). The relative contribution for this fluid outflow pathway is not understood for the healthy eye, but it may be clinically relevant in an eye with nanophthalmos (103, 104).

Molecular Mechanisms of Aqueous Humor Outflow Resistance

The biomechanical parameters and fluid hydrodynamics of the aqueous humor outflow pathways are complex. The technical challenges to study this important scientific discipline include the unique anatomy of these ocular tissues, the minute amounts of tissue available for study, and the difficulties in studying these tissues in vivo.

Resistance in the Trabecular Meshwork

Although the precise mechanism of resistance to conventional outflow is unknown, the following observations provide evidence that most resistance to conventional outflow, or trabecular outflow, is thought to be a combination of the inner wall endothelial layer and the adjacent juxtacanalicular tissues (63).

Perfusion Studies

Grant demonstrated that a 360-degree incision of the trabecular meshwork (trabeculotomy) eliminates approximately 75% of the normal outflow resistance (105). However, when such an eye is perfused at 7 mm Hg, the trabeculotomy eliminates only half the measured aqueous flow resistance (106). The remainder of the resistance to conventional aqueous humor outflow appears to be within the intrascleral outflow channels. One study in monkeys has suggested that 60% to 65% of outflow resistance is in the trabecular meshwork, 25% is in the inner one third to one half of the sclera, and 15% is in the outer one half to one third of the sclera (107).

Elevating IOP causes an increased resistance to aqueous humor outflow (108, 109), which appears to be related to a

P.19

collapse of the Schlemm canal due to distention of the trabecular meshwork, an increase in endothelial vacuoles with ballooning of the inner wall endothelial cells into the canal (83).

As might be expected from these observations, resistance to outflow is decreased by expanding the Schlemm canal. The trabecular meshwork has been described as a three-dimensional set of diagonally crossing collagen fibers, which respond to backward, inward displacement with a widening of the Schlemm canal (110). With either posterior depression of the lens or tension on the choroid (111, 112), the tension on the trabecular meshwork caused an increased outflow facility, which appeared to be due to widening of the Schlemm canal and an increase in canal inner wall porosity. Further evidence for the effect of expanding the Schlemm canal may be supported by the IOP-lowering effect of viscocanalostomy (113). In contrast, after successful filtration surgery, there is a decrease in the size of the Schlemm canal, most likely due to underperfusion of the meshwork (114).

The pattern of aqueous humor circulation within the Schlemm canal is not fully understood. Perfusion studies in enucleated human adult eyes suggest that aqueous humor cannot flow more than 10 degrees within the canal (211), although there is less resistance to circumferential flow in infant eyes (212).

However, studies of segmental blood reflux into the Schlemm canal imply that the canal is normally entirely open and that there is circumferential flow (213).

Other perfusion studies using tracer elements showed relatively free flow through the trabecular spaces and juxtacanalicular connective tissue until reaching the inner surface of the inner wall endothelium of the Schlemm canal. However, microspheres of smaller size than those used to determine flow dimensions in a perfused eye are captured by “stick y wall” interactions (115). This artifact may limit the information gained from perfusion studies concerning the dimensions of the flowlimiting passages in the conventional outflow system.

Morphology Changes

The normal human trabecular meshwork undergoes several changes with age. The general configuration changes from a long, wedge shape (Fig. 1.8) to a shorter, more rhomboidal form (116). The scleral spur becomes more prominent, the uveal meshwork becomes more compact, and localized closures in the Schlemm canal are present. The trabecular beams progressively thicken, and the endothelial cellularity declines at the rate of approximately 0.58% of cells per year, occasionally leading to trabecular denuding (117, 118). A decrease in the number of giant vacuoles and of the cell count in the Schlemm canal is explained by an age-related reduction in the size of the Schlemm canal (119). In addition to these changes, the intertrabecular spaces narrow, and extracellular material increases, especially electron-dense plaques near the juxtacanalicular tissue that is associated with the ciliary muscle tendons inserting on the scleral spur (116, 118) with age.

In COAG, there is a marked loss of trabecular meshwork cells leading to fusion and thickening of trabecular lamellae and a significant increase in electron-dense plaques compared with age-matched controls owing to components of the extracellular matrix that adhere to the sheaths of the elastic fibers and their connections to the inner wall endothelium (118). In steroid-induced glaucoma (also discussed further in the “Glucocorticoid Mechanisms” section) , an increase in fine fibrillar material stains for collagen type IV in the subendothelial region of the Schlemm canal. In pigmentary glaucoma, cell loss is more prominent than in eyes with COAG presumably due to overload with pigment granules that were visible in remaining trabecular meshwork cells. The denuded trabecular meshwork areas were collapsed, and there were areas of disorganized cribriform regions and collapse of the Schlemm canal. These occluded areas had no pigment granules.

Extracellular Matrix

The extracellular matrix within basement membranes and stroma of the trabecular meshwork plays an important mechanism for regulating IOP. The extracellular matrix is composed of fibrillar and nonfibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans, and proteoglycans (120). The extracellular matrix of the outflow pathway is dynamic, undergoing constant turnover and remodeling in response to mechanically induced IOP stretching through cell adhesion proteins, cell surface receptors, associated binding proteins, certain cytokines, growth factors, and drugs (121).

The glycosaminoglycans have been extensively studied as a component of the extracellular matrix in the trabecular meshwork. Recently in an organ culture perfusion study, outflow facility was increased at least threefold in porcine eyes and 1.5-fold in human eyes by disrupting glycosaminoglycan biosynthesis with chlorate, an inhibitor of sulfation, and with (ß-xyloside, which provides a competitive nucleatio n point for addition of disaccharide units (122). In the control eyes, immunostaining for chondroitin and heparan sulfates was intensely staining the juxtacanalicular tissue region. In treated eyes, staining was severely reduced and showed prominent plaques.

Overall in the trabecular meshwork and endothelium of the Schlemm canal, fibrinolysis is favored as a protective mechanism against obstruction from fibrin and platelets (123). In addition to facilitating the resolution of fibrin clots, tissue plasminogen activator may also influence resistance to aqueous humor outflow under normal circumstances by altering the glycoprotein content of the extracellular matrix (84). Glucocorticoid Mechanisms

The effects of glucocorticoids in the trabecular outflow pathway are complex, with both physiologic and pharmacologic implications. Glucocorticoids inhibit the synthesis of endogenous prostaglandins (124), which is clinically relevant because certain prostaglandins increase IOP in high doses but reduce ocular tension in moderate to low concentrations (see Chapter 28). Glucocorticoid receptors have been

demonstrated in trabeculectomy specimens from human glaucomatous eyes, nonglaucomatous autopsy eyes, and cultured human trabecular cells (125, 126). Glucocorticoids may influence the outflow facility by a direct effect on the extracellular matrix metabolism and the cytoskeleton (127, 128).

P.20

The role of myocilin, previously called TIGR, expression in the trabecular outflow pathways is not fully understood, but it is clinically important given its role in juvenile glaucoma (see Chapter 8) (129). Some studies have shown that myocilin expression is increased in trabecular meshwork in response to dexamethasone (130), but it is curious that patients who have steroid-induced glaucoma do not have myocilin mutations (131).

Cellular and Cytoskeletal Mechanisms

The trabecular endothelial cells have been shown to phagocytize and degrade foreign material (132); to phagocytize pigment granules observed in eyes with pigmentary glaucoma (118); and to engulf debris, detach from the trabecular core, and leave in the Schlemm canal (78). A general mechanism that contributes to decreased function of trabecular meshwork cells is progressive accumulation of damaged proteins with age due to oxidative stress and to a decline in the cellular proteolytic machinery that eliminates misfolded and damaged proteins (133).

Altering trabecular meshwork resistance through the cytoskeleton has been shown in different experimental models. In a perfusion model with substances that are known to disrupt the microfilaments, such as cytochalasins, EDTA, or H-7, monkey eyes showed significantly reduced resistance to aqueous humor outflow, and histology showed alterations in the trabecular meshwork or inner wall of the Schlemm canal (134). In a perfusion model with sulfhydryl reagents, including iodoacetamide, N- ethylmaleimide, and ethacrynic acid, facility of outflow increased owing to an alteration of cell membrane sulfhydryl groups at multiple sites in the endothelial lining of the Schlemm canal and is not due to a metabolic inhibition (135, 136, 137 and 138).

Another mechanism by which sulfhydryl groups might modulate aqueous humor outflow involves hydrogen peroxide, a normal constituent of aqueous humor, which may reduce outflow through oxidative damage of the trabecular meshwork. Calf trabecular meshwork contains the sulfhydryl compound, glutathione, as well as the enzyme glutathione peroxidase, which catalyzes the reaction between glutathione and hydrogen peroxide, thereby detoxifying the latter and presumably protecting the meshwork from its harmful effects (139). In the pig eye, oxidative damage increases outflow facility at normal pressure but decreases it with elevated IOP, suggesting that elevated pressure may increase susceptibility of the outflow pathway to this form of stress (140).

Resistance to Unconventional Outflow

Our understanding of the unconventional outflow system is based more on physiology than on anatomy, and further study is needed to correlate function and anatomy in this system. In general terms, the uveoscleral pathway is characterized as “pressure i ndependent,” is reduced by cholinergic agonists (Chapter 32), decreases with aging, and is enhanced by prostaglandin drugs (Chapter 28) (97). In both humans and monkeys, there is a decline in uveoscleral outflow with aging (64, 141). A potential explanation for the observed decline in uveoscleral outflow with aging is thickening of elastic fibers in the ciliary muscles (141).

Episcleral Venous Pressure

As discussed earlier in this chapter, another factor that contributes to the IOP is episcleral venous pressure. The precise interrelationship between episcleral venous pressure and aqueous humor dynamics is complex and is only partially understood. It has been commonly thought that for each mm Hg increase in episcleral venous pressure the IOP increases one mm Hg, although it may be that the magnitude of IOP increase is greater than the increase in venous pressure (142). The normal episcleral venous pressure is reported to be within the range of 8 to 11 mm Hg (143); however, these values are influenced considerably by the particular technique of measurement (as discussed in Chapter 3).

KEY POINTS

Our understanding of the embryology of these ocular structures has advanced considerably from studies in human genetics, cellular and molecular biology, and transgenic animals.

The basic chemistry of the aqueous humor is known. The multiple functions of this dynamic fluid include maintaining IOP, providing substrates and removing metabolites from the ocular structures, delivering high concentrations of ascorbate, participating in local paracrine signaling and immune responses, and providing a colorless and transparent medium as a part of the eye's optical system.

We have considerable knowledge about the morphology of the ciliary body; however, we do not yet fully understand the molecular mechanisms that regulate circadian rhythm, hormonal effects, and aging impact on aqueous humor production.

We have considerable knowledge about the morphology of the trabecular and uveoscleral outflow pathways in health and aging; however, we do not yet fully understand the molecular mechanisms that regulate outflow through these pathways. In general, it is thought that most resistance to outflow is due to a combination of the inner wall endothelial layer and adjacent juxtacanalicular tissues.

REFERENCES

1.Hogan M, Alvarado JA, Weddell JE. Histology of the Human Eye. Philadelphia: WB Saunders; 1971.

2.Hairston RJ, Maguire AM, Vitale S, et al. Morphometric analysis of pars plana development in humans. Retina. 1997;17(2):135-138.

3.Aiello AL, Tran VT, Rao NA. Postnatal development of the ciliary body and pars plana. A morphometric study in childhood. Arch Ophthalmol. 1992; 110(6):802-805.

4.International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004;431(7011): 931-945.

5.Lam TC, Chun RK, Li KK, et al. Application of proteomic technology in eye research: a mini review. Clin Exp Optom. 2008;91(1):23-33.

6.Wistow G. The NEIBank project for ocular genomics: data-mining gene expression in human and rodent eye tissues. Prog Retin Eye Res. 2006; 25(1):43-77.

7.Vopalensky P, Kozmik Z. Eye evolution: common use and independent recruitment of genetic components. Philos Trans R Soc Lond B Biol Sci. 2009;364(1531):2819-2832.

P.21

8.Barishak YR. Embryology of the Eye and Its Adnexa. 2nd ed. Basel, Switzerland: Karger; 2001.

9.Barishak RY, Ofri R. Embryogenetics: gene control of the embryogenesis of the eye. Vet Ophthalmol. 2007;10(3):133-136.

10.Beebe DC. Homeobox genes and vertebrate eye development. Invest Ophthalmol Vis Sci. 1994;35 (7):2897-2900.

11.Kastner P, Grondona JM, Mark M, et al. Genetic analysis of RXR alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell. 1994;78 (6):987-1003.

12.Livesey FJ, Cepko CL. Vertebrate neural cell-fate determination: lessons from the retina. Nat Rer Neurosci. 2001;2(2):109-118.

13.Zhao S, Chen Q, Hung FC, et al. BMP signaling is required for development of the ciliary body. Development. 2002;129(19):4435-4442.

14.Reichman EF, Beebe DC. Changes in cellular dynamics during the development of the ciliary epithelium. Dev Dyn. 1992;193(2):125-135.

15.Sellheyer K, Spitznas M. Surface morphology of the human ciliary body during prenatal development. A scanning electron microscopic study. Graefes Arch Clin Exp Ophthalmol. 1988;226 (1):78-83.

16.Sowden JC. Molecular and developmental mechanisms of anterior segment dysgenesis. Eye (Lond). 2007;21(10): 1310-1318.

17.Wordinger RJ, Clark AF. Bone morphogenetic proteins and their receptors in the eye. Exp Biol Med (Maywood). 2007;232(8):979-992.

18.Choy KW, Wang CC, Ogura A, et al. Genomic annotation of 15,809 ESTs identified from pooled early gestation human eyes. Physiol Genomics. 2006;25(1):9-15.

19.Funk R, Rohen JW. Scanning electron microscopic study on the vasculature of the human anterior eye segment, especially with respect to the ciliary processes. Exp Eye Res. 1990;51(6):651-661.

20.Morrison JC, DeFrank MP, Van Buskirk EM. Comparative microvascular anatomy of mammalian ciliary processes. Invest Ophthalmol Vis Sci. 1987;28(8):1325-1340.

21.Smelser GK. Electron microscopy of a typical epithelial cell and of the normal human ciliary process. Trans Am Acad Ophthalmol Otolaryngol. 1966;70(5):738-754.

22.Kitada S, Shapourifar-Tehrani S, Smyth RJ, et al. Characterization of human and rabbit pigmented and nonpigmented ciliary body epithelium. Curr Eye Res. 1991;10(5):409-415.

23.Bourge JL, Robert AM, Robert L, et al. Zonular fibers, multimolecular composition as related to function (elasticity) and pathology. Pathol Biol (Paris). 2007;55(7):347-359.

24.Marshall GE, Konstas AG, Abraham S, et al. Extracellular matrix in aged human ciliary body: an immunoelectron microscope study. Invest Ophthalmol Vis Sci. 1992;33(8):2546-2560.

25.Eichhorn M, Flugel C, Lutjen-Drecoll E. Regional differences in the distribution of cytoskeletal filaments in the human and bovine ciliary epithelium. Graefes Arch Clin Exp Ophthalmol. 1992;230 (4):385-390.

26.Zhang D, Vetrivel L, Verkman AS. Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. J Gen Physiol. 2002;119(6):561-569.

27.Preston GM, Smith BL, Zeidel ML, et al. Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels. Science. 1994;265(5178):1585-1587.

28.Raviola G, Raviola E. Intercellular junctions in the ciliary epithelium. Invest Ophthalmol Vis Sci. 1978;17(10):958-981.

29.Civan MM, Macknight AD. The ins and outs of aqueous humour secretion. Exp Eye Res. 2004;78 (3):625-631.

30.Tamm ER, Lutjen-Drecoll E. Ciliary body. Microsc Res Tech. 1996;33(5): 390-439.

31.Maren T. The rates of movement of Na+, Cl-, and HCO-3 from plasma to posterior chamber: effect of acetazolamide and relation to the treatment of glaucoma. Invest Ophthalmol. 1976; 15:356-364.

32.Tsukaguchi H, Tokui T, Mackenzie B, et al. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature. 1999;399(6731):70-75.

33.Reddy VN. Dynamics of transport systems in the eye. Friedenwald Lecture. Invest Ophthalmol Vis Sci. 1979;18(10):1000-1018.

34.McLaren JW. Measurement of aqueous humor flow. Exp Eye Res. 2009;88(4):641-647.

35.Brubaker RF. Clinical measurements of aqueous dynamics: implications for addressing glaucoma. In: Civan MM, ed. The Eye's Aqueous Humor, From Secretion to Glaucoma. New York, NY: Academic Press; 1998:234-284.

36.Radenbaugh PA, Goyal A, McLaren NC, et al. Concordance of aqueous humor flow in the morning and at night in normal humans. Invest Ophthalmol Vis Sci. 2006;47(11):4860-4864.

37.Sit AJ, Nau CB, McLaren JW, et al. Circadian variation of aqueous dynamics in young healthy adults. Invest Ophthalmol Vis Sci. 2008;49(4): 1473-1479.

38.Hayashi M, Yablonski ME, Boxrud C, et al. Decreased formation of aqueous humour in insulindependent diabetic patients. Br J Ophthalmol. 1989;73(8):621-623.

39.Walker SD, Brubaker RF, Nagataki S. Hypotony and aqueous humor dynamics in myotonic dystrophy. Invest Ophthalmol Vis Sci. 1982;22(6): 744-751.

40.Pederson JE. Ocular hypotony. Trans Ophthalmol Soc U K. 1986;105 (pt2):220-226.

41.Larsson LI, Rettig ES, Sheridan PT, et al. Aqueous humor dynamics in low-tension glaucoma. Am J Ophthalmol. 1993; 116(5):590-593.

42.Ziai N, Dolan JW, Kacere RD, et al. The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human

eyes. Arch Ophthalmol. 1993;111(10):1351-1358.

43.Brown JD, Brubaker RF. A study of the relation between intraocular pressure and aqueous humor flow in the pigment dispersion syndrome. Ophthalmology. 1989;96( 10): 1468-1470.

44.Larsson LI, Rettig ES, Brubaker RF. Aqueous flow in open-angle glaucoma. Arch Ophthalmol. 1995;113(3):283-286.

45.Brubaker RF, Nagataki S, Townsend DJ, et al. The effect of age on aqueous humor formation in man. Ophthalmology. 1981;88(3):283-288.

46.Diestelhorst M, Krieglstein GK. The effect of the water-drinking test on aqueous humor dynamics in healthy volunteers. Graefes Arch Clin Exp Ophthalmol. 1994;232(3):145-147.

47.Adams BA, Brubaker RF. Caffeine has no clinically significant effect on aqueous humor flow in the normal human eye. Ophthalmology. 1990;97(8):1030-1031.

48.Becker B. Chemical composition of human aqueous humor: effects of acetazolamide. AMA Arch Opthalmol. 1957;57(6):793-800.

49.Reiss GR, Werness PG, Zollman PE, et al. Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals. Arch Ophthalmol. 1986;104(5):753-755.

50.Barsotti MF, Bartels SP, Freddo TF, et al. The source of protein in the aqueous humor of the normal monkey eye. Invest Ophthalmol Vis Sci. 1992;33(3):581-595.

51.Haddad A, Laicine EM, de Almeida JC. Origin and renewal of the intrinsic glycoproteins of the aqueous humor. Graefes Arch Clin Exp Ophthalmol. 1991;229(4):371-379.

52.Gabelt BT, Kaufman PL. Aqueous humor hydrodynamics. In: Kaufman P, Aim A, eds. Adler's Physiology of the Eye. 10th ed. St. Louis: Mosby; 2003:237-289.

53.De Berardinis E, Tieri O, Iuglio N, et al. The composition of the aqueous humour of man in aphakia. Acta Ophthalmol. 1966;44:64-68.

54.De Berardinis E, Tieri O, Polzella A, et al. The chemical composition of the human aqueous humour in normal and pathological conditions. Exp Eye Res. 1965;4:179-186.

55.Davson H, Luck CP. A comparative study of the total carbon dioxide in the ocular fluids, cerebrospinal fluid, and plasma of some mammalian species.J Physiol. 1956;132(2):454-464.

56.Coca-Prados M, Escribano J. New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland. Prog Retin Eye Res. 2007;26(3):239-262.

57.Laurent UB. Hyaluronate in human aqueous humor. Arch Ophthalmol. 1983;101(1):129-130.

58.Trope GE, Rumley AG. Catecholamines in human aqueous humor. Invest Ophthalmol Vis Sci. 1985;26(3):399-401.

59.Carreiro S, Anderson S, Gukasyan HJ, et al. Correlation of in vitro and in vivo kinetics of nitric oxide donors in ocular tissues. J Ocul Pharmacol Ther. 2009;25(2):105-112.

60.Khodadoust AA, Stark WJ, Bell WR. Coagulation properties of intraocular humors and cerebrospinal fluid. Invest Ophthalmol Vis Sci. 1983; 24(12):1616-1619.

61.Schlotzer-Schrehardt U, Lommatzsch J, Kuchle M, et al. Matrix metalloproteinases and their inhibitors in aqueous humor of patients with exfoliation syndrome/glaucoma and primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2003;44(3): 1117-1125.

62.Gould DB, Reedy M, Wilson LA, et al. Mutant myocilin nonsecretion in vivo is not sufficient to cause glaucoma. Mol Cell Biol. 2006;26(22): 8427-8436.

63.Tamm ER. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res. 2009;88(4):648-655.

64.Toris CB, Yablonski ME, Wang YL, et al. Aqueous humor dynamics in the aging human eye. Am J Ophthalmol. 1999;127(4):407-412.

65.Moses RA, Grodzki WJ Jr, Starcher BC, et al. Elastin content of the scleral spur, trabecular mesh, and sclera. Invest Ophthalmol Vis Sci. 1978; 17(8):817-818.

P.22

66.Tamm ER, Flugel C, Stefani FH, et al. Nerve endings with structural characteristics of mechanoreceptors in the human scleral spur. Invest Ophthalmol Vis Sci. 1994;35(3):1157-1166.

67.Spencer WH, Alvarado J, Hayes TL. Scanning electron microscopy of human ocular tissues: trabecular meshwork. Invest Ophthalmol. 1968;7(6):651-662.

68.Raviola G. Schwalbe line's cells: a new cell type in the trabecular meshwork of Macaca mulatta. Invest Ophthalmol Vis Sci. 1982;22(1):45-56.

69.Murphy CG, Yun AJ, Newsome DA, et al. Localization of extracellular proteins of the human trabecular meshwork by indirect immunofluorescence. Am J Ophthalmol. 1987;104(1):33-43.

70.Gong HY, Trinkaus-Randall V, Freddo TF. Ultrastructural immunocytochemical localization of elastin in normal human trabecular meshwork. Curr Eye Res. 1989;8(10):1071-1082.

71.Raviola G, Raviola E. Paracellular route of aqueous outflow in the trabecular meshwork and canal of Schlemm. A freeze-fracture study of the endothelial junctions in the sclerocorneal angel of the macaque monkey eye. Invest Ophthalmol Vis Sci. 1981;21(1 pt 1):52-72.

72.Gipson IK, Anderson RA. Actin filaments in cells of human trabecular meshwork and Schlemm's canal. Invest Ophthalmol Vis Sci. 1979; 18(6):547-561.

73.Iwamoto Y, Tamura M. Immunocytochemical study of intermediate filaments in cultured human trabecular cells. Invest Ophthalmol Vis Sci. 1988;29(2):244-250.

74.Diaz G, Orzalesi N, Fossarello M, et al. Coated pits and coated vesicles in the endothelial cells of trabecular meshwork. Exp Eye Res. 1982;35(2): 99-106.

75.Anderson DR. Scanning electron microscopy of primate trabecular meshwork. Am J Ophthalmol. 1971;71(1 pt 1):90-101.

76.Johnstone MA. Pressure-dependent changes in configuration of the endothelial tubules of Schlemm's canal. Am J Ophthalmol. 1974;78(4): 630-638.

77.Svedbergh B. Protrusions of the inner wall of Schlemm's canal. Am J Ophthalmol. 1976;82(6):875-

78.Grierson I, Lee WR. Erythrocyte phagocytosis in the human trabecular meshwork. Br J Ophthalmol. 1973;57(6):400-415.

79.Ethier CR. The inner wall of Schlemm's canal. Exp Eye Res. 2002; 74(2):161-172.

80.Tripathi RC. Mechanism of the aqueous outflow across the trabecular wall of Schlemm's canal. Exp Eye Res. 1971;11(1):116-121.

81.Tarkkanen A, Niemi M. Enzyme histochemistry of the angle of the anterior chamber of the human eye. Acta Ophthalmol. 1987;45:93.

82.Vegge T. Ultrastructure of normal human trabecular endothelium. Acta Ophthalmol. 1963;41:193-

83.Grierson I, Lee WR. Pressure-induced changes in the ultrastructure of the endothelium lining Schlemm's canal. Am J Ophthalmol. 1975;80(5): 863-884.

84.Ethier CR, Kamm RD, Palaszewski BA, et al. Calculations of flow resistance in the juxtacanalicular meshwork. Invest Ophthalmol Vis Sci. 1986;27(12):1741-1750.

85.Johnstone MA. The aqueous outflow system as a mechanical pump: evidence from examination of tissue and aqueous movement in human and non-human primates. J Glaucoma. 2004;13(5):421-438.

86.Epstein DL, Rohen JW. Morphology of the trabecular meshwork and inner-wall endothelium after cationized ferritin perfusion in the monkey eye. Invest Ophthalmol Vis Sci. 1991;32(1):160-171.

87.Ashton N, Brini A, Smith R. Anatomical studies of the trabecular meshwork of the normal human eye. Br J Ophthalmol. 1956;40(5):257-282.

88.Rohen JW, Rentsch FJ. [Morphology of Schlemm's canal and related vessels in the human eye]. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1968;176(4):309-329.

89.Fine BS. Structure of the trabecular meshwork and the canal of Schlemm. Trans Am Acad Ophthalmol Otolaryngol. 1966;70(5):777-790.

90.de Kater AW, Spurr-Michaud SJ, Gipson IK. Localization of smooth muscle myosin-containing cells in the aqueous outflow pathway. Invest Ophthalmol Vis Sci. 1990;31(2):347-353.

91.Ascher K. The Aqueous Veins. Biomicroscopic Study of the Aqueous Humor Elimination. Springfield, IL: Charles C Thomas; 1961.

92.Hoffmann F, Dumitrescu L. Schlemm's canal under the scanning electron microscope. Ophthalmic

Res. 1971;2:37.

93.Jocson VL, Grant WM. Interconnections of blood vessels and aqueous vessels in human eyes. Arch Ophthalmol. 1965;73:707-720.

94.Rohen JW, Funk RHW. Functional morphology of the episcleral vasculature in rabbits and dogs: presence of arteriovenous anastomoses. J Glaucoma. 1994;3:51-57.

95.Raviola G. Conjunctival and episcleral blood vessels are permeable to blood-borne horseradish peroxidase. Invest Ophthalmol Vis Sci. 1983; 24(6):725-736.

96.Hayreh SS. Orbital vascular anatomy. Eye (Lond).2006;20(10):1 130-1144.

97. Aim A, Nilsson SF. Uveoscleral outflow—a review . Exp Eye Res. 2009;88(4):760-768.

98.Emi K, Pederson JE, Toris CB. Hydrostatic pressure of the suprachoroidal space. Invest Ophthalmol Vis Sci. 1989;30(2):233-238.

99.Weinreb RN, Toris CB, Gabelt BT, et al. Effects of prostaglandins on the aqueous humor outflow pathways. Surv Ophthalmol. 2002; 47(suppl 1):S53-S64.

100.Raviola G, Butler JM. Unidirectional transport mechanism of horseradish peroxidase in the vessels of the iris. Invest Ophthalmol Vis Sci. 1984;25(7):827-836.

101.Bill A. Blood circulation and fluid dynamics in the eye. Physiol Rev. 1975;55(3):383-417.

102.Pederson JE, Toris CB. Uveoscleral outflow: diffusion or flow? Invest Ophthalmol Vis Sci. 1987;28(6):1022-1024.

103.Brockhurst RJ. Vortex vein decompression for nanophthalmic uveal effusion. Arch Ophthalmol. 1980;98(11):1987-1990.

104.Uyama M, Takahashi K, Kozaki J, et al. Uveal effusion syndrome: clinical features, surgical treatment, histologic examination of the sclera, and pathophysiology. Ophthalmology. 2000;107(3):441-

105.Grant WM. Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol. 1963;69:783-801.

106.Rosenquist R, Epstein D, Melamed S, et al. Outflow resistance of enucleated human eyes at two different perfusion pressures and different extents of trabeculotomy. Curr Eye Res. 1989;8(12):12331240.

107.Peterson WS, Jocson VL, Sears ML. Resistance to aqueous outflow in the rhesus monkey eye. Am J Ophthalmol. 1971;72(2):445-451.

108.Johnstone MA, Grant WG. Pressure-dependent changes in structures of the aqueous outflow system of human and monkey eyes. Am J Ophthalmol. 1973;75(3):365-383.

109.Brubaker RF. The effect of intraocular pressure on conventional outflow resistance in the enucleated human eye. Invest Ophthalmol. 1975; 14(4):286-292.

110.Moses RA, Arnzen RJ. The trabecular mesh: a mathematical analysis. Invest Ophthalmol Vis Sci. 1980; 19(12): 1490-1497.

111.Rosenquist RC Jr, Melamed S, Epstein DL. Anterior and posterior axial lens displacement and human aqueous outflow facility. Invest Ophthalmol Vis Sci. 1988;29(7): 1159-1164.

112.Moses RA, Grodzki WJ Jr. Choroid tension and facility of aqueous outflow. Invest Ophthalmol Vis Sci. 1977; 16(11): 1062-1064.

113.Johnson DH, Johnson M. How does nonpenetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. J Glaucoma. 2001;10(1):55-67.

114.Johnson DH, Matsumoto Y. Schlemm's canal becomes smaller after successful filtration surgery. Arch Ophthalmol. 2000; 118(9): 1251-1256.

115.Johnson M, Johnson DH, Kamm RD, et al. The filtration characteristics of the aqueous outflow system. Exp Eye Res. 1990;50(4):407-418.

116.McMenamin PG, Lee WR, Aitken DA. Age-related changes in the human outflow apparatus. Ophthalmology. 1986;93(2):194-209.

117.Alvarado J, Murphy C, Polansky J, et al. Age-related changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci. 1981;21(5): 714-727.

118.Tektas OY, Lutjen-Drecoll E. Structural changes of the trabecular meshwork in different kinds of

glaucoma. Exp Eye Res. 2009;88(4):769-775.

119.Ainsworth JR, Lee WR. Effects of age and rapid high-pressure fixation on the morphology of Schlemm's canal. Invest Ophthalmol Vis Sci. 1990;31(4):745-750.

120.Acott TS, Kelley MJ. Extracellular matrix in the trabecular meshwork. Exp Eye Res. 2008;86 (4):543-561.

121.Luna C, Li G, Liton PB, et al. Alterations in gene expression induced by cyclic mechanical stress in trabecular meshwork cells. Mol Vis. 2009; 15: 534-544.

122.Keller KE, Bradley JM, Kelley MJ, et al. Effects of modifiers of glycosaminoglycan biosynthesis on outflow facility in perfusion culture. Invest Ophthalmol Vis Sci. 2008;49(6):2495-2505.

123.Shuman MA, Polansky JR, Merkel C, et al. Tissue plasminogen activator in cultured human trabecular meshwork cells. Predominance of enzyme over plasminogen activator inhibitor. Invest Ophthalmol Vis Sci. 1988;29(3):401-405.

124.Weinreb RN, Polansky JR, Alvarado JA, et al. Arachidonic acid metabolism in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1988;29(11):1708-1712.

P.23

125.Hernandez MR, Wenk EJ, Weinstein BI, et al. Glucocorticoid target cells in human outflow pathway: autopsy and surgical specimens. Invest Ophthalmol Vis Sci. 1983;24(12):1612-1616.

126.Weinreb RN, Bloom E, Baxter JD, et al. Detection of glucocorticoid receptors in cultured human trabecular cells. Invest Ophthalmol Vis Sci. 1981;21(3):403-407.

127.Hernandez MR, Weinstein BI, Wenk EJ, et al. The effect of dexamethasone on the in vitro incorporation of precursors of extracellular matrix components in the outflow pathway region of the rabbit eye. Invest Ophthalmol Vis Sci. 1983;24(6):704-709.

128.Clark AF, Wilson K, McCartney MD, et al. Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1994;35(1):281-294.

129.Resch ZT, Fautsch MR. Glaucoma-associated myocilin: a better understanding but much more to learn. Exp Eye Res. 2009;88(4):704-712.

130.Lo WR, Rowlette LL, Caballero M, et al. Tissue differential microarray analysis of dexamethasone induction reveals potential mechanisms of steroid glaucoma. Invest Ophthalmol Vis Sci. 2003;44 (2):473-485.

131.Fingert JH, Stone EM, Sheffield VC, et al. Myocilin glaucoma. Surv Ophthalmol. 2002;47(6):547-

132.Johnson DH, Richardson TM, Epstein DL. Trabecular meshwork recovery after phagocytic challenge. Curr Eye Res. 1989;8(11):1121-1130.

133.Liton PB, Gonzalez P, Epstein DL. The role of proteolytic cellular systems in trabecular meshwork homeostasis. Exp Eye Res. 2009;88(4):724-728.

134.Kaufman PL. Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia interrogating Mother Nature: asking why, asking how, recognizing the signs, following the trail. Exp Eye Res. 2008;86(1):3-17.

135.Epstein DL, Hashimoto JM, Anderson PJ, et al. Effect of iodoacetamide perfusion on outflow facility and metabolism of the trabecular meshwork. Invest Ophthalmol Vis Sci. 1981;20(5):625-631.

136.Epstein DL, Patterson MM, Rivers SC, et al. N-ethylmaleimide increases the facility of aqueous outflow of excised monkey and calf eyes. Invest Ophthalmol Vis Sci. 1982;22(6):752-756.

137.Epstein DL, Freddo TF, Bassett-Chu S, et al. Influence of ethacrynic acid on outflow facility in the monkey and calf eye. Invest Ophthalmol Vis Sci. 1987;28(12):2067-2075.

138.Lindenmayer JM, Kahn MG, Hertzmark E, et al. Morphology and function of the aqueous outflow system in monkey eyes perfused with sulfhydryl reagents. Invest Ophthalmol Vis Sci. 1983;24(6):710-

139.Nguyen KP, Chung ML, Anderson PJ, et al. Hydrogen peroxide removal by the calf aqueous outflow pathway. Invest Ophthalmol Vis Sci. 1988;29(6):976-981.

140.Yan DB, Trope GE, Ethier CR, et al. Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes. Invest Ophthalmol Vis Sci. 1991;32(9):2515-2520.

141.Gabelt BT, Kaufman PL. Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res. 2005;24(5):612-637.

142.Brubaker RF. Determination of episcleral venous pressure in the eye. A comparison of three methods. Arch Ophthalmol. 1967;77(1):110-114.

143.Zeimer RC, Gieser DK, Wilensky JT, et al. A practical venomanometer. Measurement of episcleral venous pressure and assessment of the normal range. Arch Ophthalmol. 1983;101(9):1447-1449.

Say thanks please

Shields > SECTION I - The Basic Aspects of Glaucoma >

2 - Intraocular Pressure and Tonometry

Authors: Allingham, R. Rand

Title: Shields Textbook of Glaucoma, 6th Edition Copyright ©2011 Lippincott Williams & Wilkins

> Table of Contents > SECTION I - The Basic Aspects of Glaucoma > 2 - Intraocular Pressure and Tonometry

2

Intraocular Pressure and Tonometry INTRAOCULAR PRESSURE What Is Normal?

In individuals who are susceptible to glaucoma, “no rmal” intraocular pressure (IOP) may be defined as that pressure which does not lead to glaucomatous damage of the optic nerve head. Unfortunately, such a definition cannot be expressed in precise numerical terms because individuals show different susceptibility to optic nerve damage at given pressure levels that also depends on the underlying form of glaucoma (1, 2). The best we can do is to describe the distribution of IOP in general populations to establish levels of risk for glaucoma within different pressure ranges. This chapter considers the distribution of IOP in the general population; the factors, other than glaucoma, that may influence IOP; and the clinical techniques for measuring IOP. (In Section II, the significance of various pressure levels in populations of patients with specific types of glaucoma is considered.)

Table 2.1Reported IOP Distributions in General Populations