IV. SUMMARY

The use of animal models to investigate the circulation of aqueous humor in normal ocular health and chronic ocular diseases that disturb the IOP requires an appreciation for the diversity among species in the anatomical and physiological diVerences in the iridocorneal angle. Extrapolating animal findings to human disease requires discretion. Methods have been developed recently to measure the components of aqueous humor dynamics in the tiny murine eye, making the mouse the preferred model for genetic studies of glaucoma. Some breeds of dog suVer from spontaneous glaucoma that provides clues to the pathogenesis of glaucoma in humans. Study of these breeds has contributed to improved treatments for human as well as canine glaucoma. The monkey remains the most valuable animal model for understanding aqueous humor dynamics in human glaucoma because of its anatomical and physiological similarities to humans.

There are a myriad of methods available to assess the four main parameters of aqueous humor dynamics, aqueous flow, outflow facility, uveoscleral outflow, and episcleral venous pressure. The most accurate methods are invasive and often terminal. Methods designed for one species may not be easily adaptable for another. The noninvasive methods are indirect, highly variable, and fraught with many limitations and assumptions. Nevertheless, these methods remain useful in clinical research. Imaging techniques are evolving rapidly and may soon become suYciently sensitive to allow simultaneous visualization and quantitation of ocular hydrodynamics in a direct noninvasive manner.

Acknowledgment

Figures were made with the assistance of Richard Tamesis, MD.

References

Aihara, M., Lindsey, J. D., and Weinreb, R. N. (2003a). Aqueous humor dynamics in mice.

Invest. Ophthalmol. Vis. Sci. 44, 5168–5173.

Aihara, M., Lindsey, J. D., and Weinreb, R. N. (2003b). Episcleral venous pressure of mouse eye and eVect of body position. Curr. Eye Res. 27, 355–362.

Artru, A. A. (1995). Rate of anterior chamber aqueous formation, trabecular outflow facility, and intraocular compliance during desflurane or halothane anesthesia in dogs. Anesth. Analg. 81, 585–590.

Artru, A. A., and Momota, Y. (1999). Trabecular outflow facility and formation rate of aqueous humor during anesthesia with sevoflurane nitrous oxide or sevoflurane remifentanil in rabbits. Anesth. Analg. 88, 781–786.

Avila, M. Y., Carre´, D. A., Stone, R. A., and Civan, M. M. (2001). Reliable measurement of mouse intraocular pressure by a servo null micropipette system. Invest. Ophthalmol. Vis. Sci. 42, 1841–1846.

Avila, M. Y., Munera, A., Guzman, A., Do, C. W., Wang, Z., Stone, R. A., and Civan, M. M. (2005). Noninvasive intraocular pressure measurements in mice by pneumotonometry.

Invest. Ophthalmol. Vis. Sci. 46, 3274–3280.

Ba´ra´ny, E. H. (1964). Simultaneous measurement of changing the intraocular pressure and outflow facility in the vervet monkey by constant pressure infusion. Invest. Ophthalmol. 3, 135–143.

Barrie, K. P., Gum, G. G., Samuelson, D. A., and Gelatt, K. N. (1985). Quantitation of uveoscleral outflow in normotensive and glaucomatous beagles by 3H labeled dextran.

Am. J. Vet. Res. 46, 84–88.

Bill, A. (1966). Conventional and uveo scleral drainage of aqueous humour in the cynomolgus monkey (Macaca irus) at normal and high intraocular pressures. Exp. Eye Res. 5, 45–54.

Bill, A. (1967). Further studies on the influence of the intraocular pressure on aqueous humor dynamics in cynomolgus monkeys. Invest. Ophthalmol. 6, 364–372.

Bill, A. (1971). Aqueous humor dynamics in monkeys (Macaca irus and Cercopithecus ethiops).

Exp. Eye Res. 11, 195–206.

Bito, L. Z. (1984). Species diVerences in the responses of the eye to irritation and trauma: A hypothesis of divergence in ocular defense mechanisms, and the choice of experimental animals for eye research. Exp. Eye Res. 39, 807–829.

Bito, L. Z., Camras, C. B., Gum, G. G., and Resul, B. (1989). The ocular hypotensive eVects and side eVects of prostaglandins on the eyes of experimental animals. In ‘‘The Ocular EVects of Prostaglandins and Other Eicosanoids’’ (L. Z. Bito and J. Stjernschantz, eds.), Vol. 312, pp. 349–368. Alan R. Liss, Inc, New York, NY.

Brubaker, R. F. (1982). The flow of aqueous humor in the human eye. Trans. Am. Ophthalmol. Soc. 80, 391–474.

Brubaker, R. F. (1991). Flow of aqueous humor in humans. Invest. Ophthalmol. Vis. Sci. 32, 3145–3166.

Brubaker, R. F. (1998). Clinical measurements of aqueous dynamics: Implications for addressing glaucoma. In ‘‘The Eye’s Aqueous Humor. From Secretion to Glaucoma’’ (M. M. Civan, ed.), Vol. 45, pp. 233–284. Academic Press, San Diego.

Brubaker, R. F., Maurice, D. M., and McLaren, J. W. (1990). Fluorometry of the anterior segment. In ‘‘Noninvasive Diagnostic Techniques in Ophthalmology’’ (B. R. Masters, ed.), pp. 248–280. Springer Verlag, New York, NY.

Camras, C. B. (2003). Some thoughts on the pressure dependence of uveoscleral flow.

J. Glaucoma 12, 92–93.

Cawrse, M. A., Ward, D. A., and Hendrix, D. V. H. (2001). EVects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs. Am. J. Vet. Res. 62, 859–863.

Chang, B., Smith, R. S., Hawes, N. L., Anderson, M. G., Zabaleta, A., Savinova, O., Roderick, T. H., Heckenlively, J. R., Davisson, M. T., and John, S. W. M. (1999). Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice. Nat. Genet. 21, 405–409.

Chee, P., and Hamasaki, D. I. (1971). The basis for chymotrypsin induced glaucoma. Arch. Ophthalmol. 85, 103–106.

Chidlow, G., Cupido, A., Melena, J., and Osborne, N. N. (2001). Flesinoxan, a 5 HT1A receptor agonist/a1 adrenoceptor antagonist, lowers intraocular pressure in NZW rabbits. Curr. Eye Res. 23, 144–153.

Chien, F. Y., Wang, R. F., Mittag, T. W., and Podos, S. M. (2003). EVect of WIN 55212–2, a cannabinoid receptor agonist, on aqueous humor dynamics in monkeys. Arch. Ophthalmol. 121, 87–90.

Chu, T. C., and Potter, D. E. (2002). Ocular hypotension induced by electroacupuncture.

J. Ocul. Pharmacol. Ther. 18, 293–305.

Colasanti, B. K. (1990). A comparison of the ocular and central eVects of 9 tetrahydrocannabinol and cannabigerol. J. Ocul. Pharmacol. 6, 259–269.

Crosson, C. E. (2001). Intraocular pressure responses to the adenosine agonist cyclohexyladenosine: Evidence for a dual mechanism of action. Invest. Ophthalmol. Vis. Sci. 42, 1837–1840.

Crosson, C. E., and Petrovich, M. (1999). Contributions of adenosine receptor activation to the ocular actions of epinephrine. Invest. Ophthalmol. Vis. Sci. 40, 2054–2061.

Crowston, J. G., Aihara, M., Lindsey, J. D., and Weinreb, R. N. (2004). EVect of latanoprost on outflow facility in the mouse. Invest. Ophthalmol. Vis. Sci. 45, 2240–2245.

Dawson, W. W., Brooks, D. E., Hope, G. M., Samuelson, D. A., Sherwood, M. B., Engel, H. M., and Kessler, M. J. (1993). Primary open angle glaucomas in the rhesus monkey.

Br. J. Ophthalmol. 77, 302–310.

Diamond, J. M., and Bossert, W. H. (1967). Standing gradient osmotic flow. A mechanism for coupling of water and solute transport in epithelia. J. Gen. Physiol. 50, 2061–2083.

Ethier, C. R. (2002). The inner wall of Schlemm’s canal. Exp. Eye Res. 74, 161–172.

Fan, S., Johnson, T. V., and Toris, C. B. (2006). Measurement of intraocular pressure in mice by TonoLab tonometry. Invest. Ophthalmol. Vis. Sci. 47, 215.

Fan, S., Johnson, T. V., Liu, H., Ishimoto, B. M., and Toris, C. B. (2007). Aqueous flow measured by fluorophotometry in the mouse. Invest. Ophthalmol. Vis. Sci. 48, 3921.

Friedenwald, J. S. (1948). Some problems with the calibration of tonometers. Am. J. Ophthalmol. 31, 935–944.

Gabelt, B. T., and Kaufman, P. L. (1990). The eVect of prostaglandin F2a on trabecular outflow facility in cynomolgus monkeys. Exp. Eye Res. 51, 87–91.

Gabelt, B. T., and Kaufman, P. L. (2005). Changes in aqueous humor dynamics with age and glaucoma. Prog. Retin. Eye Res. 24, 612–637.

Gabelt, B. T., Crawford, K., and Kaufman, P. L. (1991). Outflow facility and its response to pilocarpine decline in aging rhesus monkeys. Arch. Ophthalmol. 109, 879–882.

Gabelt, B. T., Millar, C. J., Kiland, J. A., Peterson, J. A., Seeman, J. L., and Kaufman, P. L. (2001). EVects of serotonergic compounds on aqueous humor dynamics in monkeys. Curr. Eye Res. 23, 120–127.

Gabelt, B. T., Gottanka, J., Lu¨tjen Drecoll, E., and Kaufman, P. L. (2003). Aqueous humor dynamics and trabecular meshwork and anterior ciliary muscle morphologic changes with age in rhesus monkeys. Invest. Ophthalmol. Vis. Sci. 44, 2118–2125.

Gabelt, B. T., Seeman, J. L., Podos, S. M., Mittag, T. W., and Kaufman, P. L. (2004). Aqueous humor dynamics in monkeys after topical 8 iso PGE2. Invest. Ophthalmol. Vis. Sci. 45, 892–899.

Gabelt, B. T., Okka, M., Dean, T. R., and Kaufman, P. L. (2005). Aqueous humor dynamics in monkeys after topical R DOI. Invest. Ophthalmol. Vis. Sci. 46, 4691–4696.

Gelatt, K. N., Gwin, R. M., PeiVer, R. L., Jr., and Gum, G. G. (1977). Tonography in the normal and glaucomatous beagle. Am. J. Vet. Res. 38, 515–520.

Gelatt, K. N., Gum, G. G., Merideth, R. E., and Bromberg, N. (1982). Episcleral venous pressure in normotensive and glaucomatous beagles. Invest. Ophthalmol. Vis. Sci. 23, 131–135.

Goh, Y., Oshima, T., and Araie, M. (1994). Mechanism of intraocular pressure reduction observed after topical application of S 1033 in animals. Jpn. J. Ophthalmol. 38, 228–235.

Goldmann, H. (1951). Abflussdruck, minutenvolumen und widerstand der kammerwasser stro¨mung des menschen. Doc. Ophthalmol. 5–6, 278–356.

Grant, W. M. (1950). Tonographic method for measuring the facility and rate of aqueous flow in human eyes. Arch. Ophthalmol. 44, 204–214.

Grayson, M. C., and Laties, A. M. (1971). Ocular localization of sodium fluorescein. EVects of administration in rabbit and monkey. Arch. Ophthalmol. 85, 600–609.

Green, K., Sherman, S. H., Laties, A. M., Pederson, J. E., Gaasterland, D. E., and MacLellan, H. M. (1977). Fate of anterior chamber tracers in the living rhesus monkey eye with evidence for uveo vortex outflow. Trans. Ophthalmol. Soc. UK 97, 731–739.

Gross, R. L., Ji, J., Chang, P., Pennesi, M. E., Yang, Z., Zhang, J., and Wu, S. M. (2003). A mouse model of elevated intraocular pressure: Retina and optic nerve findings. Trans. Am. Ophthalmol. Soc. 101, 163–169.

Grozdanic, S. D., Betts, D. M., Sakaguchi, D. S., Allbaugh, R. A., Kwon, Y. H., and Kardon, R. H. (2003). Laser induced mouse model of chronic ocular hypertension. Invest. Ophthalmol. Vis. Sci. 44, 4337–4346.

Hayashi, M., Yablonski, M. E., and Bito, L. Z. (1987). Eicosanoids as a new class of ocular hypotensive agents. 2. Comparison of the apparent mechanism of the ocular hypotensive eVects of A and F type prostaglandins. Invest. Ophthalmol. Vis. Sci. 28, 1639–1643.

Hayashi, M., Yablonski, M. E., and Novack, G. D. (1989). Trabecular outflow facility determined by fluorophotometry in human subjects. Exp. Eye Res. 48, 621–625.

Higginbotham, E. J., Lee, D. A., Bartels, S. P., Richardson, T., and Miller, M. (1988). EVects of cyclocryotherapy on aqueous humor dynamics in cats. Arch. Ophthalmol. 106, 396–403.

Honjo, M., Inatani, M., Kido, N., Sawamura, T., Yue, B. Y., Honda, Y., and Tanihara, H. (2001). EVects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes. Arch. Ophthalmol. 119, 1171–1178.

Inoue, T., Yokoyoma, T., Mori, Y., Sasaki, Y., Hosokawa, T., Yanagisawa, H., and Koike, H. (2001). The eVect of topical CS 088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits. Curr. Eye Res. 23, 133–138.

John, S. W., Smith, R. S., Savinova, O. V., Hawes, N. L., Chang, B., Turnbull, D., Davisson, M., Roderick, T. H., and Heckenlively, J. R. (1998). Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Invest. Ophthalmol. Vis. Sci. 39, 951–962.

Johnson, M. (2006). What controls aqueous humour outflow resistance?. Exp. Eye Res. 82, 545–557.

Johnson, T. V., Fan, S., and Toris, C. B. (2008). Rebound tonometry in conscious, conditioned mice avoids the acute and profound effects of anesthesia on intraocular pressure. J. Ocular Pharmacol. Therapeutics. 24, 175–185.

Kanno, M., Araie, M., Tomita, K., and Sawanobori, K. (1998). EVects of topical nipradilol, a b blocking agent with a blocking and nitroglycerin like activities, on aqueous humor dynamics and fundus circulation. Invest. Ophthalmol. Vis. Sci. 39, 736–743.

Kee, C., and Seo, K. (1997). The eVect of interleukin 1a on outflow facility in rat eyes.

J. Glaucoma 6, 246–249.

Kee, C., Hong, T., and Choi, K. (1997). A sensitive ocular perfusion apparatus measuring outflow facility. Curr. Eye Res. 16, 1198–1201.

Kiel, J. W., and Reitsamer, H. A. (2007). Paradoxical eVect of phentolamine on aqueous flow in the rabbit. J. Ocul. Pharmacol. Ther. 23, 21–26.

Kiel, J. W., Reitsamer, H. A., Walker, J. S., and Kiel, F. W. (2001). EVects of nitric oxide synthase inhibition on ciliary blood flow, aqueous production and intraocular pressure.

Exp. Eye Res. 73, 355–364.

Koskela, T., and Brubaker, R. F. (1991). The nocturnal suppression of aqueous humor flow in humans is not blocked by bright light. Invest. Ophthalmol. Vis. Sci. 32, 2504–2506.

Kotikoski, H., Vapaatalo, H., and Oksala, O. (2003). Nitric oxide and cyclic GMP enhance aqueous humor outflow facility in rabbits. Curr. Eye Res. 26, 119–123.

Krohn, J., and Bertelsen, T. (1997). Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the human eye. Acta Ophthalmol. 75, 32–35.

Kurata, K., Fujimoto, H., Tsukuda, R., Suzuki, T., Ando, T., and Tokuriki, M. (1998). Aqueous humor dynamics in beagle dogs with caVeine induced ocular hypertension. J. Vet. Med. Sci. 60, 737–739.

Lee, P. Y., Podos, S. M., Howard Williams, J. R., Severin, C. H., Rose, A. D., and Siegel, M. J. (1985). Pharmacological testing in the laser induced monkey glaucoma model. Curr. Eye Res. 4, 775–781.

Levene, R. Z., Rothberger, M., and Rosenberg, S. (1974). Corticosteroid glaucoma in the rabbit.

Am. J. Ophthalmol. 78, 505–510.

Lu¨tjen Drecoll, E. (1999). Functional morphology of the trabecular meshwork in primate eyes.

Prog. Retin. Eye Res. 18, 91–119.

Ma¨epea, O., and Bill, A. (1989). The pressures in the episcleral veins, Schlemm’s canal and the trabecular meshwork in monkeys: EVects of changes in intraocular pressure. Exp. Eye Res. 49, 645–663.

Maurice, D. M. (1963). A new objective fluorophotometer. Exp. Eye Res. 2, 33–38.

McLaren, J. W., Brubaker, R. F., and FitzSimon, J. S. (1996). Continuous measurement of intraocular pressure in rabbits by telemetry. Invest. Ophthalmol. Vis. Sci. 37, 966–975.

McMaster, P. R. B., and Macri, F. J. (1968). Secondary aqueous humor outflow pathways in the rabbit, cat, and monkey. Arch. Ophthalmol. 79, 297–303.

Melena, J., Santafe´, J., Segarra Domenech, J., and Puras, G. (1999). Aqueous humor dynamics in a chymotrypsin induced ocular hypertensive rabbits. J. Ocul. Pharmacol. Ther. 15, 19–27.

Mermoud, A., Baerveldt, G., Minckler, D. S., Prata, J. A., Jr., and Rao, N. A. (1996). Aqueous humor dynamics in rats. Graefes Arch. Clin. Exp. Ophthalmol. 234, S198–S203.

Morrison, J. C., Moore, C. G., Deppmeier, L. M. H., Gold, B. G., Meshul, C. K., and Johnson, E. C. (1997). A rat model of chronic pressure induced optic nerve damage. Exp. Eye Res. 64, 85–96.

Muta, K., Tamaki, Y., Araie, M., and Matsubara, M. (2000). EVect of ifenprodil on aqueous humor dynamics and optic nerve head circulation in rabbits. J. Ocul. Pharmacol. Ther. 16, 241–250.

Nguyen, C. T. O., Bui, B. V., Sinclair, A. J., and Vingrys, A. J. (2007). Dietary omega 3 fatty acids decrease intraocular pressure with age by increasing aqueous outflow. Invest. Ophthalmol. Vis. Sci. 48, 756–762.

Nilsson, S. F. E., Drecoll, E., Lu¨tjen Drecoll, E., Toris, C. B., Krauss, A. H. P., Kharlamb, A., Nieves, T., Guerra, T., and Woodward, D. F. (2006). The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey. Invest. Ophthalmol. Vis. Sci. 47, 4042–4049.

Ogidigben, M. J., and Potter, D. E. (2001). Central imidazoline (I1) receptors modulate aqueous hydrodynamics. Curr. Eye Res. 22, 358–366.

Oka, T., Taniguchi, T., Kitazawa, Y., Sagara, T., and Nishida, T. (2006). Aqueous humor dynamics associated with the phorbol ester induced decrease in intraocular pressure in the rabbit. Jpn. J. Ophthalmol. 50, 497–503.

Okka, M., Tian, B., and Kaufman, P. L. (2004). EVects of latrunculin B on outflow facility, intraocular pressure, corneal thickness, and miotic and accommodative responses to pilocarpine in monkeys. Trans. Am. Ophthalmol. Soc. 102, 251–257.

Oksala, O., and Stjernschantz, J. (1988). Increase in outflow facility of aqueous humor in cats induced by calcitonin gene related peptide. Exp. Eye Res. 47, 787–790.

Pease, M. E., Hammond, J. C., and Quigley, H. A. (2006). Manometric calibration and comparison of TonoLab and Tono Pen tonometers in rats with experimental glaucoma and in normal mice. J. Glaucoma 15, 512–519.

Pederson, J. E., and Gaasterland, D. E. (1984). Laser induced primate glaucoma. I. Progression of cupping. Arch. Ophthalmol. 102, 1689–1692.

Pederson, J. E., Gaasterland, D. E., and MacLellan, H. M. (1977). Uveoscleral aqueous outflow in the rhesus monkey: Importance of uveal reabsorption. Invest. Ophthalmol. Vis. Sci. 16, 1008–1017.

PeiVer, R. L., Jr., Gelatt, K. N., and Gum, G. G. (1976). Determination of the facility of aqueous humor outflow in the dog, comparing in vivo and in vitro tonographic and constant pressure perfusion techniques. Am. J. Vet. Res. 37, 1473–1477.

PeiVer, R. L., Jr., Gum, G. G., Grimson, R. C., and Gelatt, K. N. (1980). Aqueous humor outflow in beagles with inherited glaucoma: Constant pressure perfusion. Am. J. Vet. Res. 41, 1808–1813.

Peterson, J. A., Tian, B., Geiger, B., and Kaufman, P. L. (2000a). EVect of latrunculin B on outflow facility in monkeys. Exp. Eye Res. 70, 307–313.

Peterson, J. A., Tian, B., McLaren, J. W., Hubbard, W. C., Geiger, B., and Kaufman, P. L. (2000b). Latrunculins’ eVects on intraocular pressure, aqueous humor flow, and corneal endothelium. Invest. Ophthalmol. Vis. Sci. 41, 1749–1758.

Podos, S. M., Camras, C. B., Serle, J. B., and Lee, P. Y. (1987). Pharmacologic alteration of aqueous humor dynamics in normotensive and glaucomatous monkey eyes. In ‘‘Glaucoma Update III’’ (G. K. Krieglstein, ed.), pp. 225–235. Springer Verlag, Berlin.

Puras, G., Santafe´, J., Segarra, J., Garrido, M., and Melena, J. (2002a). EVects of topical natural ergot alkaloids on intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits. J. Ocul. Pharmacol. Ther. 18, 41–52.

Puras, G., Santafe´, J., Segarra, J., Garrido, M., and Melena, J. (2002b). The eVect of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in rabbits with a chymotrypsin induced ocular hypertension. Graefes Arch. Clin. Exp. Ophthalmol. 240, 322–328.

Quigley, H. A., and Hohman, R. M. (1983). Laser energy levels for trabecular meshwork damage in the primate eye. Invest. Ophthalmol. Vis. Sci. 24, 1305–1307.

Reiss, G. R., Lee, D. A., Topper, J. E., and Brubaker, R. F. (1984). Aqueous humor flow during sleep. Invest. Ophthalmol. Vis. Sci. 25, 776–778.

Reitsamer, H. A., and Kiel, J. W. (2002). A rabbit model to study orbital venous pressure, intraocular pressure, and ocular hemodynamics simultaneously. Invest. Ophthalmol. Vis. Sci. 43, 3728–3734.

Reitsamer, H. A., Kiel, J. W., Harrison, J. M., Ransom, N. L., and McKinnon, S. J. (2004). Tono Pen measurement of intraocular pressure in mice. Exp. Eye Res. 78, 799–804.

Rosenberg, L. F., Karalekas, D. P., Krupin, T., and Hyderi, A. (1996). Cyclocryotherpay and noncontact Nd:YAG laser cyclophotocoagulation in cats. Invest. Ophthalmol. Vis. Sci. 37, 2029–2036.

Ruiz Ederra, J., and Verkman, A. S. (2006). Mouse model of sustained elevation in intraocular pressure produced by episcleral vein occlusion. Exp. Eye Res. 82, 879–884.

Russell, K. R. M., Wang, D. R., and Potter, D. E. (2000). Modulation of ocular hydrodynamics and iris function by bremazocine, a kappa opioid receptor agonist. Exp. Eye Res. 70, 675–682.

Schnell, C. R., Debon, C., and Percicot, C. L. (1996). Measurement of intraocular pressure by telemetry in conscious, unrestrained rabbits. Invest. Ophthalmol. Vis. Sci. 37, 958–965.

Shareef, S. R., Garcia Valenzuela, E., Salierno, A., Walsh, J., and Sharma, S. C. (1995). Chronic ocular hypertension following episcleral venous occlusion in rats. Exp. Eye Res. 61, 379–382.

Silver, D. M., and Farrell, R. A. (1994). Validity of pulsatile ocular blood flow measurements.

Surv. Ophthalmol. 38, S72–S80.

Skorobohach, B. J., Ward, D. A., and Hendrix, D. V. H. (2003). EVects of oral administration of methazolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs. Am. J. Vet. Res. 64, 183–187.

Smith, S. D., and Gregory, D. S. (1989). A circadian rhythm of aqueous flow underlies the circadian rhythm of IOP in NZW rabbits. Invest. Ophthalmol. Vis. Sci. 30, 775–778.

Sperber, G. O., and Bill, A. (1984). A method for near continuous determination of aqueous humor flow; eVects of anaesthetics, temperature and indomethacin. Exp. Eye Res. 39, 435–453.

Sugiyama, T., Kida, T., Mizuno, K., Kojima, S., and Ikeda, T. (2001). Involvement of nitric oxide in the ocular hypotensive action of nipradilol. Curr. Eye Res. 23, 346–351.

Suguro, K., Toris, C. B., and Pederson, J. E. (1985). Uveoscleral outflow following cyclodialysis in the monkey eye using a fluorescein tracer. Invest. Ophthalmol. Vis. Sci. 26, 810–813.

Takagi, Y., Nakajima, T., Shimazaki, A., Kageyama, M., Matsugi, T., Matsumura, Y., Gabelt, B. T., Kaufman, P. L., and Hara, H. (2004). Pharmacological characteristics of AFP 168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug.

Exp. Eye Res. 78, 767–776.

Tian, B., and Kaufman, P. L. (2005). EVects of the Rho kinase inhibitor Y 27632 and the phosphatase inhibitor calyculin A on outflow facility in monkeys. Exp. Eye Res. 80, 215–225.

Tian, B., Wang, R. F., Podos, S. M., and Kaufman, P. L. (2004). EVects of topical H 7 on outflow facility, intraocular pressure, and corneal thickness in monkeys. Arch. Ophthalmol. 122, 1171–1177.

Toris, C. B., and Pederson, J. E. (1985). EVect of intraocular pressure on uveoscleral outflow following cyclodialysis in the monkey eye. Invest. Ophthalmol. Vis. Sci. 26, 1745–1749.

Toris, C. B., Yablonski, M. E., Wang, Y. L., and Hayashi, M. (1995). Prostaglandin A2 increases uveoscleral outflow and trabecular outflow facility in the cat. Exp. Eye Res. 61, 649–657.

Toris, C. B., Yablonski, M. E., Wang, Y. L., and Camras, C. B. (1999). Aqueous humor dynamics in the aging human eye. Am. J. Ophthalmol. 127, 407–412.

Toris, C. B., Zhan, G. L., Wang, Y. L., Zhao, J., McLaughlin, M. A., Camras, C. B., and Yablonski, M. E. (2000). Aqueous humor dynamics in monkeys with laser induced glaucoma. J. Ocul. Pharmacol. Ther. 16, 19–27.

Toris, C. B., Koepsell, S. A., Yablonski, M. E., and Camras, C. B. (2002). Aqueous humor dynamics in ocular hypertensive patients. J. Glaucoma 11, 253–258.

Toris, C. B., Zhan, G. L., and McLaughlin, M. A. (2003). EVects of brinzolamide on aqueous humor dynamics in monkeys and rabbits. J. Ocul. Pharmacol. Ther. 19, 397–404.

Toris, C. B., Zhan, G. L., Camras, C. B., and McLaughlin, M. A. (2005). EVects of travoprost on aqueous humor dynamics in monkeys. J. Glaucoma 14, 70–73.

Toris, C. B., Lane, J. T., Akagi, Y., Blessing, K. A., and Kador, P. F. (2006a). Aqueous flow in galactose fed dogs. Exp. Eye Res. 83, 865–870.

Toris, C. B., Zhan, G. L., Feilmeier, M. R., Camras, C. B., and McLaughlin, M. A. (2006b). EVects of a prostaglandin DP receptor agonist, AL 6598, on aqueous humor dynamics in a nonhuman primate model of glaucoma. J. Ocul. Pharmacol. Ther. 22, 86–92.

Toris, C. B., Dawson, W. W., and McLaughlin, M. A. (2007). Aqueous humor dynamics in Rhesus monkeys with naturally occurring ocular hypertension. Invest. Ophthalmol. Vis. Sci. 48, 4894.

Wang, J., Song, Y., Ren, B., Sun, N., Yu, Y., and Hu, H. (2003). DiVerent eVects of topical prazosin and pilocarpine on uveoscleral outflow in rabbit eyes. Yan Ke Xue Bao 19, 191–194.

Wang, W. H., Millar, J. C., Pang, I. H., Wax, M. B., and Clark, A. F. (2005). Noninvasive measurement of rodent intraocular pressure with a rebound tonometer. Invest. Ophthalmol. Vis. Sci. 46, 4617–4621.

Wang, Y. L., Toris, C. B., Zhan, G., and Yablonski, M. E. (1999). EVects of topical epinephrine on aqueous humor dynamics in the cat. Exp. Eye Res. 68, 439–445.

Ward, D. A., Cawrse, M. A., and Hendrix, D. V. H. (2001). Fluorophotometric determination of aqueous humor flow rate in clinically normal dogs. Am. J. Vet. Res. 62, 853–858.

WoldeMussie, E., Ruiz, G., Wijono, M., and Wheeler, L. A. (2001). Neuroprotection of retinal ganglion cells by brimonidine in rats with laser induced chronic ocular hypertension. Invest. Ophthalmol. Vis. Sci. 42, 2849–2855.

Zeimer, R. C. (1989). Episcleral venous pressure. In ‘‘The Glaucomas’’ (R. Ritch, M. B. Shields, and T. Krupin, eds.), pp. 249–255. The C. V. Mosby Company, St. Louis.

Zhan, G. L., Miranda, O. C., and Bito, L. Z. (1992). Steroid glaucoma: Corticosteroid induced ocular hypertension in cats. Exp. Eye Res. 54, 211–218.

Zhan, G. L., Toris, C. B., Camras, C. B., Wang, Y. L., and Yablonski, M. E. (1998). Bunazosin reduces intraocular pressure in rabbits by increasing uveoscleral outflow. J. Ocul. Pharmacol. Ther. 14, 217–228.

Zhan, G. L., Lee, P. Y., Ball, D. C., Mayberger, C. J., Tafoya, M. E., Camras, C. B., and Toris, C. B. (2002). Time dependent eVects of sympathetic denervation on aqueous humor dynamics and choroidal blood flow in rabbits. Curr. Eye Res. 25, 99–105.

Zhang, D., Vetrivel, L., and Verkman, A. S. (2002). Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. J. Gen. Physiol. 119, 561–569.

Zhu, M. D., and Cai, F. Y. (1992). Development of experimental chronic intraocular hypertension in the rabbit. Aust. N. Z. J. Ophthalmol. 20, 225–234.