Ophthalmic drug discovery

Nature Reviews Drug Discovery

Volumn 2, Issue 6, 2003, Pages 448-459

  Clark, Abbot F ^a,b   Yorio, Thomas ^a  

^a ALCON RESEARCH LTD   (United States)

^b UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (5 ISOQUINOLINESULFONYL) 2 METHYLPIPERAZINE; AGENTS ACTING ON THE EYE; ANGIOGENESIS INHIBITOR; ANTIGLAUCOMA AGENT; BIMATOPROST; BUMETANIDE; CHELERYTHRINE; CHOLINERGIC RECEPTOR STIMULATING AGENT; CYCLOSPORIN; ETACRYNIC ACID; FUMAGILLIN; LATANOPROST; LATRUNCULIN A; LATRUNCULIN B; LOTEPREDNOL ETABONATE; MACROLIDE; METALLOPROTEINASE INHIBITOR; MYOCILIN; NONSTEROID ANTIINFLAMMATORY AGENT; PILOCARPINE; PROSTAGLANDIN DERIVATIVE; PROSTAGLANDIN F2 ALPHA DERIVATIVE; PROTEIN KINASE C INHIBITOR; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIMEXOLONE; RUBOXISTAURIN; STAUROSPORINE; SWINHOLIDE A; TRAVOPROST; UNINDEXED DRUG; EYE DROPS; NEUROPROTECTIVE AGENT;

BLINDNESS; CATARACT; CONJUNCTIVITIS; DIABETIC RETINOPATHY; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG PENETRATION; DRUG TARGETING; DRY EYE; EYE DISEASE; EYE INFECTION; GLAUCOMA; HUMAN; KERATITIS; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RETINA MACULA AGE RELATED DEGENERATION; REVIEW; UVEITIS; ANIMAL; METABOLISM; METHODOLOGY; PHARMACEUTICS; VISUAL DISORDER;

ANIMALS; DRUG DELIVERY SYSTEMS; GLAUCOMA; HUMANS; NEUROPROTECTIVE AGENTS; OPHTHALMIC SOLUTIONS; TECHNOLOGY, PHARMACEUTICAL; VISION DISORDERS;

EID: 0038132019     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd1106     Document Type: Review

References (168)

1. Alward, W. L. Biomedicine. A new angle on ocular development. Science 299, 1527-1528 (2003).
2. Vision problems in the U. S. (2002) Prevent Blindness America; National Eye Institute. www.nei.nih.gov/eyedata/.
3. Clark, A. F. Current trends in antiglaucoma therapy. Emerging Drugs 4, 333-353 (1999).
4. Alward, W. L. M. Glaucoma: The Requisites in Ophthalmology. 1-260 (Mosby, St Louis, 2000).
5. Fraser, S. & Wormald, R. in Ophthalmology (eds Yanoff, M. & Duker, J. S.) 12:1.1-12:1.6 (Mosby, London, 1999).
6. Wirtz, M. K. & Samples, J. R. in Glaucoma: Science and Practice (eds Morrison, J. C. & Pollack, I. P.) 12-21 (Thieme Medical, New York, 2003).
7. Wudunn, D. Genetic basis of glaucoma. Curr. Opin. Ophthalmol. 13, 55-60 (2002).
8. Stone, E. M. et al. Identification of a gene that causes primary open angle glaucoma. Science 275, 668-670 (1997).
9. Vittitow, J. & Borras, T. Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure. Biochem. Biophys. Res. Commun. 298, 67-74 (2002).
10. Rezaie, T. et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 295, 1077-1079 (2002).
11. Kass, M. A. et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch. Ophthalmol. 120, 701-713; discussion 829-730 (2002).
12. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am. J. Ophthalmol. 130, 429-440 (2000).
13. Clark, A. F. & Pang, I.-H. Advances in glaucoma therapeutics. Expert Opin. Emerging Drugs 7, 141-163 (2002).
14. Medeiros, F. A. & Weinreb, R. N. Medical backgrounders: glaucoma. Drugs Today (Barc.) 38, 563-570 (2002).
15. Bradley, J. M. et al. Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Invest. Ophthalmol. Vis. Sci. 39, 2649-2658 (1998).
16. Wong, T. T. et al. Matrix metalloproteinases in disease and repair processes in the anterior segment. Surv. Ophthalmol. 47, 239-256 (2002).
17. Parshley, D. E., Bradley, J. M., Samples, J. R., Van Buskirk, E. M. & Acott, T. S. Early changes in matrix metalloproteinases and inhibitors after In vitro laser treatment to the trabecular meshwork. Curr. Eye Res. 14, 537-544 (1995).
18. Parshley, D. E. et al. Laser trabeculoplasty induces stromelysin expression by trabecular juxtacanalicular cells. Invest. Ophthalmol. Vis. Sci. 37, 795-804 (1996).
19. Pang, I.-H., Fleenor, D. L., Hellberg, P. E., Stropki, K., McCartney, M. D. & Clark, A. F. Aqueous outflow-enhancing effect of tert-butylhydroquinone: involvement of AP-1 activation and MMP-3 expression. Invest. Ophthalmol. Vis. Sci. (In the press).
20. Lindsey, J. D. et al. Prostaglandins increase proMMP-1 and proMMP-3 secretion by human ciliary smooth muscle cells. Curr. Eye Res. 15, 869-875 (1996).
21. Weinreb, R. N., Kashiwagi, K., Kashiwagi, F., Tsukahara, S. & Lindsey, J. D. Prostaglandins increase matrix metalloproteinase release from human ciliary smooth muscle cells. Invest. Ophthalmol. Vis. Sci. 38, 2772-2780 (1997).
22. Quigley, H. A. Experimental glaucoma damage mechanism. Arch. Ophthalmol. 101, 1301-1302 (1983).
23. Halpern, D. L. & Grosskreutz, C. L. Glaucomatous optic neuropathy: mechanisms of disease. Ophthalmol. Clin. North Am. 15, 61-68 (2002).
24. Fechtner, R. D. & Weinreb, R. N. Mechanisms of optic nerve damage in primary open angle glaucoma. Surv. Ophthalmol. 39, 23-42 (1994).
25. Wordinger, R. J. & Clark, A. F. Effects of glucocorticoids or the trabecular meshwork: towards a better understanding of glaucoma. Prog. Retin. Eye Res. 18, 629-667 (1999).
26. Neufeld, A. H. Nitric oxide: a potential mediator of retinal ganglion cell damage in glaucoma. Surv. Ophthalmol. 43 Suppl 1, S129-135 (1999).
27. Vorwerk, C. K., Gorla, M. S. & Dreyer, E. B. An experimental basis for implicating excitotoxicity in glaucomatous optic neuropathy. Surv. Ophthalmol. 43, S142-150 (1999).
28. Tezel, G. & Wax, M. B. Increased production of tumor necrosis factor-α by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. J. Neurosci. 20, 8693-8700 (2000).
29. Yorio, T., Krishnamoorthy, R. & Prasanna, G. Endothelin: is it a contributor to glaucoma pathophysiology? J. Glaucoma 11, 259-270 (2002).
30. Pang, I.-H. & Yorio, T. Ocular actions of endothelins. Proc. Soc. Exp. Biol. Med. 215, 21-34 (1997).
31. Wax, M. B., Yang, J. & Tezel, G. Serum autoantibodies in patients with glaucoma. J. Glaucoma 10, S22-24 (2001).
32. Schwartz, M. Physiological approaches to neuroprotection. Boosting of protective autoimmunity. Surv. Ophthalmol. 45, S256-260; discussion S273-276 (2001).
33. Aihara, M., Lindsey, J. D. & Weinreb, R. N. Reduction of intraocular pressure in mouse eyes treated with latanoprost. Invest. Ophthalmol. Vis. Sci. 43, 146-150 (2002).
34. Avila, M. Y., Carre, D. A., Stone, R. A. & Civan, M. M. Reliable measurement of mouse intraocular pressure by a servo-null micropipette system. Invest. Ophthalmol. Vis. Sci. 42, 1841-1846 (2001).
35. Fanous, M. M., Challa, P. & Maren, T. H. Comparison of intraocular pressure lowering by topical and systemic carbonic anhydrase inhibitors in the rabbit. J. Ocul. Pharmacol. Ther. 15, 51-57 (1999).
36. Wang, R. F., Serle, J. B., Gagliuso, D. J. & Podos, S. M. Comparison of the ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears added to timolol in glaucomatous monkey eyes. J. Glaucoma 9, 458-462 (2000).
37. Morrison, J. C., Nylander, K. B., Lauer, A. K., Cepurna, W. O. & Johnson, E. Glaucoma drops control intraocular pressure and protect optic nerves in a rat model of glaucoma. Invest. Ophthalmol. Vis. Sci. 39, 526-531 (1998).
38. Pederson, J. E. & Gaasterland, D. E. Laser-induced primate glaucoma. I. Progression of cupping. Arch. Ophthalmol. 102, 1689-1692 (1984).
39. Zhu, M. D. & Cai, F. Y. Development of experimental chronic intraocular hypertension in the rabbit. Aust. N. Z. J. Ophthalmol. 20, 225-234 (1992).
40. Morrison, J. C. et al. A rat model of chronic pressure-induced optic nerve damage. Exp. Eye Res. 64, 85-96 (1997).
41. Anderson, M. G. et al. Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nature Genet. 30, 81-85 (2002).
42. Shareef, S. R., Garcia-Valenzuela, E., Salierno, A., Walsh, J. & Sharma, S. C. Chronic ocular hypertension following episcleral venous occlusion in rats. Exp. Eye Res. 61, 379-382 (1995).
43. Mittag, T. W. et al. Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model. Invest. Ophthalmol. Vis. Sci. 41, 3451-3459 (2000).
44. Ueda, J. et al. Experimental glaucoma model in the rat induced by laser trabecular photocoagulation after an intracameral injection of India ink. Jpn. J. Ophthalmol. 42, 337-344 (1998).
45. Wheeler, L. A. & Woldemussie, E. α-2 adrenergic receptor agonists are neuroprotective in experimental models of glaucoma. Eur. J. Ophthalmol. 11, S30-35 (2001).
46. Levkovitch-Verbin, H. et al. Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats. Invest. Ophthalmol. Vis. Sci. 43, 402-410 (2002).
47. Garcia-Valenzuela, E., Shareef, S., Walsh, J. & Sharma, S. C. Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp. Eye Res. 61, 33-44 (1995).
48. Johnson, E. C., Deppmeier, L. M., Wentzien, S. K., Hsu, I. & Morrison, J. C. Chronology of optic nerve head and retinal responses to elevated intraocular pressure. Invest. Ophthalmol. Vis. Sci. 41, 431-442 (2000).
49. Cioffi, G. A., Orgul, S., Onda, E., Bacon, D. R. & van Buskirk, E. M. An in vivo model of chronic optic nerve ischemia: the dose-dependent effects of endothelin-1 on the optic nerve microvasculature. Curr. Eye Res. 14, 1147-1153 (1995).
50. Flammer, J., Pache, M. & Resink, T. Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. Prog. Retin. Eye Res. 20, 319-349 (2001).
51. Stokely, M. E., Brady, S. T. & Yorio, T. Effects of endothelin-1 on components of anterograde axonal transport in optic nerve, Invest. Ophthalmol. Vis. Sci. 43, 3223-3230 (2002).
52. Krishnamoorthy, R. R. et al. Characterization of a transformed rat retinal ganglion cell line. Brain Res. Mol. Brain Res. 86, 1-12 (2001).
53. Pang, I.-H., McCartney, M. D., Steely, H. T. & Clark, A. F. Human ocular perfusion organ culture: a versatile ex vivo model for glaucoma research. J. Glaucoma 9, 468-479 (2000).
54. Clark, A. F., Wilson, K., De Kater, A. W., Allingham, R. R. & McCartney, M. D. Dexamethasone-induced ocular hypertension in perfusion-cultured human eyes. Invest. Ophthalmol. Vis. Sci. 36, 478-489 (1995).
55. Borras, T, Brandt, C. R., Nickells, R. & Fitch, R. Gene therapy for glaucoma: treating a multifaceted, chronic disease. Invest. Ophthalmol. Vis. Sci. 43, 2513-2518 (2002).
56. Clark, A. F., Lane, D., Wilson, K., Miggians, S. T. & McCartney, M. D. Inhibition of dexamethasone-induced cytoskeletal changes in cultured human trabecular meshwork cells by tetrahydrocortisol. Invest. Ophthalmol. Vis. Sci. 37, 805-813 (1996).
57. Fleenor, D. L., Pang, I.-H. & Clark, A. F. Involvement of AP-1 in interleukin-1α-stimulated MMP-3 expression in human trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci. (in the press).
58. Benson, W. E. in Ophthalmology (eds Yanoff, M. & Duker, J. S.) 8:20.1-28:20.10 (Mosby, London, 1999).
59. Aiello, L. P. Vascular endothelial growth factor and the eye: biochemical mechanisms of action and implications for novel therapies. Ophthalmic Res. 29, 354-362 (1997).
60. Gardner, T. W., Antonetti, D. A., Barber, A. J., Lanoue, K. F. & Levison, S. W. Diabetic retinopathy: more than meets the eye. Surv. Ophthalmol. 47, S253-262 (2002).
61. Barber, A. J. A new view of diabetic retinopathy: a neuro-degenerative disease of the eye. Prog. Neuropsychopharmacol. Biol. Psychiatry. 27, 283-290 (2003).
62. Engerman, R. L. & Kern, T. S. Retinopathy in galactosemic dogs continues to progress after cessation of galactosemia. Arch. Ophthalmol. 113, 355-358 (1995).
63. Kowluru, R. A. Retinal metabolic abnormalities in diabetic mouse: comparison with diabetic rat. Curr. Eye Res. 24, 123-128 (2002).
64. Robison, W. G. Jr, Nagata, M., Laver, N., Hohman, T. C. & Kinoshita, J. H. Diabetic-like retinopathy in rats prevented with an aldose reductase inhibitor. Invest Ophthalmol. Vis. Sci. 30, 2285-2292 (1989).
65. Fong, D. S. Changing times for the management of diabetic retinopathy. Surv. Ophthalmol. 47, S238-245 (2002).
66. Lund-Andersen, H. Mechanisms for monitoring changes in retinal status following therapeutic intervention in diabetic retinopathy. Surv. Ophthalmol. 47, S270-277 (2002).
67. Aiello, F. P. The potential role of PKC β in diabetic retinopathy and macular edema. Surv. Ophthalmol. 47 Suppl 2, S263-269 (2002).
68. Jaffe, G. J. et al. Safety and pharmacokinetics of an intraocular fluocinolone acetonide sustained delivery device. Invest. Ophthalmol. Vis. Sci. 41, 3569-3575 (2000).
69. Ciulla, T A., Criswell, M. H., Danis, R. P. & Hill, T. E. Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model. Arch. Ophthalmol. 119, 399-404 (2001).
70. Martidis, A. et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 109, 920-927 (2002).
71. Edwards, M. G., Bressler, N. M. & Raja, S. C. in Ophthalmology (eds Yanoff, M. & Duker, J. S.) 8:28.1-28:28.10 (Mosby, London, 1999).
72. Husain, D., Ambati, B., Adams, A. P. & Miller, J. W. Mechanisms of age-related macular degeneration. Ophthalmol. Clin. North Am. 15, 87-91 (2002).
73. Crabb, J. W. et al. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc. Natl Acad. Sci. USA 99, 14682-14687 (2002).
74. Hageman, G. S. et al. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration. Prog. Retin. Eye Res. 20, 705-732 (2001).
75. Anderson, D. H., Mullins, R. F., Hageman, G. S. & Johnson, L. V. A role for local inflammation in the formation of drusen in the aging eye. Am. J. Ophthalmol. 134, 411-431 (2002).
76. Agarwal, N. et al. Levobetaxolol-induced up-regulation of retinal bFGF and CNTF mRNAs and preservation of retinal function against a photic-induced retinopathy. Exp. Eye Res. 74, 445-453 (2002).
77. Seiler, M. J. et al. Selective photoreceptor damage in albino rats using continuous blue light. A protocol useful for retinal degeneration and transplantation research. Graefes. Arch. Clin. Exp. Ophthalmol. 238, 599-607 (2000).
78. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, β-carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol. 119, 1417-1436 (2001).
79. Okamoto, N. et al. Transgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subretinal neovascularization. Am. J. Pathol. 151, 281-291 (1997).
80. Penn, J. S. & Henry, M. M. Assessing retinal neovascularization in an animal model of proliferative retinopathy. Microvasc. Res. 51, 126-130 (1996).
81. Robinson, G. S. et al. Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc. Natl Acad. Sci. USA 93, 4851-4856 (1996).
82. Griggs, J. et al. Inhibition of proliferative retinopathy by the anti-vascular agent combretastatin-A4. Am. J. Pathol. 160. 1097-1103 (2002).
83. Garcia, C. et al. Efficacy of Prinomastat (AG3340), a matrix metalloprotease inhibitor, in treatment of retinal neovascularization. Curr. Eye Res. 24, 33-38 (2002).
84. Bainbridge, J. W. et al. Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther. 9, 320-326 (2002).
85. Murata, T. et al. Response of experimental retinal neovascularization to thiazolidinediones. Arch. Ophthalmol. 119, 709-717 (2001).
86. Smith, L. E. et al. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276, 1706-1709 (1997).
87. Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Retina 22, 143-152 (2002).
88. Presta, L. G. et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 57, 4593-4599 (1997).
89. Krzystolik, M. G. et al. Prevention of experimental chemical neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch. Ophthalmol. 120, 338-346 (2002).
90. Das, A., McLamore, A., Song, W., McGuire, P. G. Retinal neovascularization is suppressed with a matrix metalloproteinase inhibitor. Arch. Ophthalmol. 117, 498-503 (1999).
91. 5 in ocular neovascular diseases. Proc. Natl Acad. Sci. USA 93, 9764-9769 (1996).
92. Clark, A. F., Bingaman, D. P. & Kapin, M. A. Ocular angiostatic agents. Expert Opin. Ther. Patents 10, 427-448 (2000).
93. Clark, A. F. AL-3789: a novel ophthalmic angiostatic steroid, Exp. Opin. Invest. Drugs 6, 1867-1877 (1997).
94. Penn, J. S., Rajaratnam, V. S., Collier, R. J. & Clark, A. F. The effect of an angiostatic steroid on neovascularization in a rat model of retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. 42, 283-290 (2001).
95. Rechtman, E., Ciulla, T. A., Criswell, M. H., Pollack, A. & Harris, A. An update on photodynamic therapy in age-related macular degeneration. Expert Opin. Pharmacother. 3, 931-938 (2002).
96. Sieving, P. A. in Ophthalmology (eds Yanoff, M. & Duker, J. S.) 8:11.1-18:11.10. (Mosby, London, 1999).
97. Zack, D. J. et al. What can we learn about age-related macular degeneration from other retinal diseases? Mol. Vis. 5, 30 (1999).
98. Stone, E. M., Sheffield, V. C. & Hageman, G. S. Molecular genetics of age-related macular degeneration. Hum. Mol. Genet. 10, 2285-2292 (2001).
99. Allikmets, R. et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy Nature Genet, 15, 236-246 (1997).
100. Weber, B. H., Vogt, G., Pruett, H. C., Stohr, H. & Felbor, U. Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nature Genet. 8, 352-356 (1994).
101. Petrukhin, K. et al. Identification of the gene responsible for Best macular dystrophy. Nature Genet. 19, 241-247 (1998).
102. Stone, E. M. et al. A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy. Nature Genet. 22, 199-202 (1999).
103. Stone, E. M. et al. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Nature Genet. 20, 328-329 (1998).
104. de la Paz, M. A., Pericak-Vance, M. A., Lennon, F., Haines, J. L. & Seddon, J. M. Exclusion of TIMP3 as a candidate locus in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 38, 1060-1065 (1997).
105. Allikmets, R. et al. Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies. Hum. Genet. 104, 449-453 (1999).
106. Felbor, U., Doepner, D., Schneider, U., Zrenner, E. & Weber, B. H. Evaluation of the gene encoding the tissue inhibitor of metalloproteinases-3 in various maculopathies. Invest. Ophthalmol. Vis. Sci. 38, 1054-1059 (1997).
107. Weber, B. H. et al. A mouse model for Sorsby fundus dystrophy Invest. Ophthalmol. Vis. Sci. 43, 2732-2740 (2002).
108. Rakoczy, P. E. et al. Progressive age-related changes similar to age-related macular degeneration in a transgenic mouse model. Am. J. Pathol. 161, 1515-1524 (2002).
109. Fauser, S., Luberichs, J. & Schuttauf, F. Genetic animal models for retinal degeneration. Surv. Ophthalmol. 47, 357-367 (2002).
110. Chang, B. et al. Retinal degeneration mutants in the mouse. Vision Res. 42, 517-525 (2002).
111. Chader, G. J. Animal models in research on retinal degenerations: past progress and future hope. Vision Res. 42, 393-399 (2002).
112. 2+ antagonist. Invest. Ophthalmol. Vis. Sci. 43, 919-926 (2002).
113. McGee Sanftner, L. H., Abel, H., Hauswirth, W. W. & Flannery, J. G. Glial cell line delved neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa. Mol. Ther. 4, 622-629 (2001).
114. Liang, F. Q. et al. AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse. Mol. Ther. 3, 241-248 (2001).
115. Campochiaro, P. A. Gene therapy for retinal and choroidal diseases. Expert Opin. Biol. Ther. 2, 537-544 (2002).
116. Acland, G. M. et al. Gene therapy restores vision in a canine model of childhood blindness. Nature Genet. 28, 92-95 (2001).
117. Bielory, L. Update on ocular allergy treatment. Expert Opin. Pharmacother. 3, 541-553 (2002).
118. Bielory, L. Ocular allergy guidelines: a practical treatment algorithm. Drugs 62, 1611-1634 (2002).
119. Yanni, J. M. et al. A current appreciation of sites for pharmacological intervention in allergic conjunctivitis: effects of new topical ocular drugs. Acta Ophthalmol. Scand. Suppl. 228, 33-37 (1999).
120. Kunert, K. S., Tisdale, A. S. & Gipson, I. K. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch. Ophthalmol. 120, 330-337 (2002).
121. Fujihara, T., Murakami, T., Fujita, H., Nakamura, M. & Nakata, K. Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model. Invest. Ophthalmol. Vis. Sci. 42, 96-100 (2001).
122. Calonge, M. The treatment of dry eye. Surv. Ophthalmol. 45, S227-239 (2001).
123. Nelson, M. L. & Martidis, A. Managing cystoid macular edema after cataract surgery. Curr. Opin. Ophthalmol. 14, 39-43 (2003).
124. Foster, C. S. et al. Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis. Am. J. Ophthalmol. 122, 171-182 (1996).
125. Leibowitz, H. M. et al. Intraocular pressure-raising potential of 1.0% rimexolone in patients responding to corticosteroids. Arch. Ophthalmol. 114, 933-937 (1996).
126. Bodor, N. Retrometabolic drug design-novel aspects, future directions, Pharmazie 56, S67-74 (2001).
127. Howes, J. F. Loteprednol etabonate: a review of ophthalmic clinical studies. Pharmazie 55, 178-183 (2000).
128. Thielen, T. L, Castle, S. S. & Terry, J. E. Anterior ocular infections: an overview of pathophysiology and treatment. Ann. Pharmacother. 34, 235-246 (2000).
129. Guembel, H. O. & Ohrloff, C. Opportunistic infections of the eye in immunocompromised patients, Ophthalmologica 211, 53-61 (1997).
130. Smith, A., Pennefather, P. M., Kaye, S. B. & Hart, C. A. Fluoroquinolones: place in ocular therapy. Drugs 61, 747-761 (2001).
131. Goldstein, M. H., Kowalski, R. P. & Gordon, Y. J. Emerging fluoroquinolone resistance in bacterial keratitis: a 5-year review. Ophthalmology 106, 1313-1318 (1999).
132. Schoenwall R. D. in Textbook of Ocular Pharmacology. (eds Zimmerman, T. J., Kooner, K. S., Sharir, M. & Fechtner, R. D.) 119-138 (Lippincott-Raven, Philadelphia, 1997).
133. Sasaki, H. et al. Enhancement of ocular drug penetration. Crit. Rev. Ther. Drug. Carrier Syst. 16, 85-146 (1999).
134. Kaur, I. P. & Kanwar, M. Ocular preparations: the formulation approach. Drug Dev. Ind. Pharm. 28, 473-493 (2002).
135. Loftsson, T. & Stefansson, E. Cyclodextrins in eye drop formulations: enhanced topical delivery of corticosteroids to the eye. Acta Ophthalmol. Scand. 80, 144-150 (2002).
136. Kaur, I. P. & Smitha R. Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic drug delivery. Drug Dev. Ind. Pharm. 213, 353-369 (2002).
137. Kimura, H. & Ogura, Y. Biodegradable polymers for ocular drug delivery. Ophthalmologica 215, 143-155 (2001).
138. Geroski, D. H. & Edelhauser, H. F. Transscleral drug delivery for posterior segment disease. Adv. Drug Deliv. Rev. 52, 37-48 (2001).
139. Ke, T. L., Clark, A. F. & Gracy, R. W. Age-related permeability changes in rabbit corneas. J. Ocul. Pharmacol. Ther. 15, 513-523 (1999).
140. Sheffield, V. C. et al. Genetic linkage of familial open angle glaucoma to chromosome 1q21-q31. Nature Genet. 4, 47-50 (1993).
141. Fauss, D. J. et al. in Basic Aspects of Glaucoma Research III (ed. Lutjen-Drecoll, E.) 319-330 (Schattauer, New York, 1993).
142. Nguyen, T. D. et al. Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells. J. Biol. Chem. 273, 6341-6350 (1998).
143. Kubota, R. et al. A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping. Genomics 41, 360-369 (1997).
144. Fingert, J. H. et al. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum. Mol. Genet. 8, 899-905 (1999).
145. Fingert, J. H., Stone, E. M., Sheffield, V. C. & Alward, W. L. Myocilin glaucoma. Surv. Ophthalmol. 47, 547-561 (2002).
146. Alward, W. L. et al. Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A). N. Engl. J. Med. 338, 1022-1027 (1998).
147. Alward, W. L. et al. Variations in the myocilin gene in patients with open-angle glaucoma. Arch. Ophthalmol. 120, 1189-1197 (2002).
148. Tamm, E. R. Myocilin and glaucoma: facts and ideas. Prog. Retin. Eye Res. 21, 395-428 (2002).
149. Lam, D. S. et al. Truncations in the TIGR gene in individuals with and without primary open-angle glaucoma. Invest. Ophthalmol. Vis. Sci. 41, 1386-1391 (2000).
150. Kim, B. S. et al. Targeted disruption of the myocilin gene (Myoc) suggests that human glaucoma-causing mutations are gain of function. Mol. Cell Biol. 21, 7707-7713 (2001).
151. Clark, A. F. et al. Glucocorticoid induction of the glaucoma gene MYOC in human and monkey trabecular meshwork cells and tissues. Invest. Ophthalmol. Vis. Sci. 42, 1769-1780 (2001).
152. Filla, M. S. et al. In vitro localization of TIGR/MYOC in trabecular meshwork extracellular matrix and binding to fibronectin. Invest. Ophthalmol. Vis. Sci. 43, 151-161 (2002).
153. Fingert, J. H. et al. Evaluation of the myocilin (MYOC) glaucoma gene in monkey and human steroid-induced ocular hypertension. Invest. Ophthalmol. Vis. Sci. 42, 145-152 (2001).
154. Fautsch, M. P., Bahler, C. K., Jewison, D. J. & Johnson, D. H. Recombinant TIGR/MYOC increases outflow resistance in the human anterior segment. Invest. Ophthalmol. Vis. Sci. 41, 4163-4168 (2000).
155. Caballero, M., Rowlette, L. L. & Borras, T. Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain. Biochim. Biophys. Acta 1502, 447-460 (2000).
156. Jacobson, N. et al. Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor. Hum. Mol. Genet. 10, 117-125 (2001).
157. Zhou, Z. & Vollrath, D. A cellular assay distinguishes normal and mutant TIGR/myocilin protein. Hum. Mol. Genet. 8, 2221-2228 (1999).
158. Klein, B. E., Klein, R. & Lee, K. E. Incidence of age-related cataract over a 10-year interval: the Beaver Dam Eye Study, Ophthalmology 109, 2052-2057 (2002).
159. Panchapakesan, J. et al. Five year incidence of cataract surgery: the Blue Mountains Eye Study. Br. J. Ophthalmol. 87, 168-172 (2003).
160. McKinnon, S. J. et al. Baculoviral IAP repeat-cortaining-4 protects optic nerve axons in a rat glaucoma model. Mol. Ther. 5, 780-787 (2002).
161. Tatton, W. G. Apoptotic mechanisms in neurodegeneration possible relevance to glaucoma. Eur. J. Ophthalmol. 9, S22-29 (1999).
162. Hare, W. et al. Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey. Surv. Ophthalmol. 45, S284-289; discussion S295-286 (2001).
163. Wood, J. P., Desantis, L., Chao, H. M. & Osborne, N. N. Topically applied betaxalol attenuates ischaemia-induced effects to the rat retina and stimulates BDNF mRNA. Exp. Eye Res. 72, 79-86 (2001).
164. Neufeld, A. H., Sawada, A. & Becker, B. Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc. Natl Acad. Sci. USA 96, 9944-9948 (1999).
165. Tatton, W. G., Chalmers-Redman, R. M. & Tatton, N. A. Apoptosis and anti-apoptosis signalling in glaucomatous retinopathy. Eur. J. Ophthalmol. 11, S12-22 (2001).
166. Nakazawa, T., Tamai M. & Mori, N. Brain-derived neurotrophic factor prevents axotomized retinal ganglion cell death through MAPK and PI3K signaling pathways. Invest. Ophthalmol. Vis. Sci. 43, 3319-3326 (2002).
167. Ko, M. L., Hu, D. N., Ritch, R., Sharma, S. C. & Chen, C.F. Patterns of retinal ganglion cell survival after brain-derived neurotropric factor administration in hypertensive eyes of rats. Neurosci. Lett. 305, 139-142 (2001).
168. Zhou, J. et al. Characterization of RGS5 in regulator of G protein-coupled receptor signaling. Life Sci. 68, 1457-1469 (2001).