Conclusion

The major sight-threatening diseases are glaucoma, AMD, and diabetic retinopathy. Intense research is ongoing to find more potent and efficacious drugs with reduced side-effect potential to treat these diseases. Traditional research centered around receptor-based pharmaceutics, but now more emphasis seems to be directed toward discovering and developing enzyme inhibitors. Furthermore, agents that impart multiple therapeutically useful activities, for instance IOP-lowering and retinoprotective agents, are being actively pursued to add value to the treatment of these ocular diseases. A better ability to noninvasively diagnose and treat retinal diseases and dysfunctions at an earlier stage would greatly enhance the overall success rate of treatment. The generation of novel techniques (e.g., proteomics and gene therapy) and reagents such as small interfering RNA (siRNA)100 may represent tomorrow's 'drugs' to treat ocular diseases such as AMD, diabetic retinopathy, and glaucoma. We look forward to such advances in the drug discovery/ development and disease diagnosis processes.

References

2. Clark, A. C.; Yorio, T Nat. Rev. Drug Disc. 2003, 2, 448-459.

3. Pang, I.-H.; Wang, W-H.; Clark, A. C. Exp. Eye Res. 2005, 80, 207-214.

4. Allingham, R. R.; Wiggs, J. L.; Hauser, E. R.; Larocque-Abramson, K. R.; Santiago-Turla, C.; Broomer, B.; Del Bono, E. A.; Graham, F L.; Haines, J. L.; Pericak-Vance, M. A. et al. Invest. Ophthalmol. Vis. Sci. 2005, 46, 2002-2005.

5. Kincaid, M. C. In Age-Related Macular Degeneration: Principles and Practice; Hampton, G. R., Nelson, P T, Eds.; Raven Press: New York, 1992, Chapter 2, pp 37-61.

6. Clemons, T E.; Milton, R. C.; Klein, R.; Seddon, J. M.; Ferris, F L., III. Ophthalmology 2005, 112, 533-539.

7. Friedman, E. Br. J. Ophthalmol. 2004, 88, 161-163.

8. Friedman, D. S.; O'Colmain, B. J.; Munoz, B.; Tomany, S. C.; McCarty, C.; de Jong, P T; Nemesure, B.; Mitchell, P.; Kempen, J. Arch. Ophthalmol. 2004, 4, 564-572.

9. Congdon, N.; O'Colmain, B.; Klaver, C. C.; Klein, R.; Munoz, B.; Friedman, D. S.; Kempen, J.; Taylor, H. R.; Mitchell, P Arch. Ophthalmol. 2004, 122, 477-485.

10. Fuchshofer, R.; Welge-Lussen, U.; Luten-Drecoll, E. Exp. Eye Res. 2003, 77, 757-765.

11. Choi, J.; Miller, A. M.; Nolan, M. J.; Yue, B. Y J. T; Thotz, S. T; Clark, A. C.; Agarwal, N.; Knepper, P. A. Invest. Ophthalmol. Vis. Sci. 2005, 46, 214-222.

12. Urieli-Shoval, S.; Cohen, P; Eisenberg, S.; Matzner, Y J. Histochem. Cytochem. 1998, 46, 1377-1384.

13. McKinnon, S. J.; Lehman, D. M.; Kerrigan-Baumrind, L. A.; Merges, C. A.; Pease, M. E.; Kerrigan, D. F; Ransom, N. L.; Tahzib, N. G.; Reitsamer, H. A.; Levkovitch-Verbin, H. et al. Invest. Ophthalmol. Vis. Sci. 2002, 43, 1077-1087.

14. Guo, Li.; Moss, S. E.; Alexander, R. A.; Ali, R. R.; Fitzke, F W; Cordeiro, M. F Invest. Ophthalmol. Vis. Sci. 2004, 46, 175-182.

15. Zarbin, M. A. Arch. Ophthalmol. 2004, 122, 598-614.

16. Hageman, G. S.; Luthert, P. J.; Chong, N. H. V; Johnson, L. V; Anderson, D. H.; Mullins, R. F Prog. Ret. Eye Res. 2001, 20, 705-732.

17. Anderson, D. H.; Talaga, K. C.; Rivest, A. J.; Barron, E.; Hageman, G. S.; Johnson, L. V Exp. Eye Res. 2004, 78, 243-256.

18. Anderson, D. H.; Mullins, R. F; Hageman, G. S.; Johnson, L. V Am. J. Ophthalmol. 2002, 134, 411-431.

19. Ben-Shabat, S.; Parish, C. A.; Hashimoto, M.; Liu, J.; Nakanishi, K.; Sparrow, J. R. Bioorg. Med. Chem. Lett. 2001, 11, 1533-1540.

20. Pawlak, A.; Wrona, M. Photochem. Photobiol. 2003, 77, 253-258.

21. Azarian, S. M.; Travis, G. H. FEBS Lett. 1997, 409, 247-252.

22. Allikmets, R.; Shroyer, N. F; Singh, N.; Seddon, J. M.; Lewis, R. A.; Bernstein, P. S.; Peiffer, A.; Zabriskie, N. A.; Li, Y; Hutchinson, A. et al. Science 1997, 277, 1805-1807.

23. Evans, J. R.; Fletcher, A. E.; Wormald, R. P Br. J. Ophthalmol. 2005, 89, 550-553.

24. Seddon, J. M.; George, S.; Rosner, B.; Rifai, N. Arch. Ophthalmol. 2005, 123, 774-782.

25. Klein, R. J.; Zeiss, C.; Chew, E. Y.; Tsai, J. Y.; Sackler, R. S.; Haynes, C.; Henning, A. K.; SanGiovanni, J. P.; Mane, S. M.; Mayne, S. T. et al.

Science 2005, 308, 385-389.

26. Haines, J. L.; Hauser, M. A.; Schmidt, S.; Scott, W. K.; Olson, L. M.; Gallins, P.; Spencer, K. L.; Kwan, S. Y.; Noureddine, M.; Gilbert, J. R. et al. Science 2005, 308, 419-421.

27. Kijlstra, A.; La Heij, E.; Hendrikse, F Ocul. Immunol. Inflamm. 2005, 13, 3-11.

28. Miller, D. M.; Espinosa-Heidmann, D. G.; Legra, J.; Dubovy, S. R.; Suner, I. J.; Sedmak, D. D.; Dix, R. D.; Cousins, S. W Am. J. Ophthalmol. 2004, 138, 323-328.

29. Zareparsi, S.; Reddick, A. C.; Branham, K. E.; Moore, K. B.; Jessup, L.; Thoms, S.; Smith-Wheelock, M.; Yashar, B. M.; Swaroop, A. Invest. Ophthalmol. Vis. Sci. 2004, 45, 1306-1310.

30. Schmidt, S.; Klaver, C.; Saunders, A.; Postel, E.; De La Paz, M.; Agarwal, A.; Small, K.; Udar, N.; Ong, J.; Chalukya, M. et al. Ophthalmic Genet. 2002, 23, 209-223.

31. van Leeuwen, R.; Klaver, C. C.; Vingerling, J. R.; Hofman, A.; van Duijn, C. M.; Stricker, B. H.; de Jong, P T Am. J. Ophthalmol. 2004, 137, 750-752.

32. Malek, G.; Johnson, L. V; Mace, B. E.; Saloupis, P.; Schmechel, D. E.; Rickman, D. W; Toth, C. A.; Sullivan, P M.; Rickman, C. B. Proc. Natl. Acad. Sci. USA 2005, 102, 11900-11905.

33. Sharif, N. A.; Williams, G. W; Crider, J. Y; Xu, S. X.; Davis, T. L. J. Ocular Pharmacol. Ther. 2004, 20, 489-508.

34. Weinreb, R. N.; Lindsey, J. D. Invest. Ophthalmol. Vis. Res. 2002, 43, 716-722.

35. Sharif, N. A.; Kelly, C. R.; Crider, J. Y; Senchyna, M. Invest. Ophthalmol. Vis. Sci. 2005, Suppl. Abst. 3688.

36. Pang, I.-H.; McCartney, M. D.; Steeley, H. T; Clark, A. C. J. Glaucoma 2000, 9, 468-479.

37. Anderson, M. G.; Smith, R. S.; Hawes, N. L.; Zabaleta, A.; Chang, B.; Wiggs, J. L.; John, S. W Nature Genet. 2002, 30, 81-85.

38. May, J. M.; McLaughlin, M. A.; Sharif, N. A.; Hellberg, M. R.; Dean, T R. J. Pharmacol. Expt. Ther. 2003, 306, 301-309.

39. Pang, I.-H.; Wang, W-H.; Millar, J. C.; Clark, A. C. Exp. Eye Res. 2005, 81, 359-360.

40. Moreno, M. C.; Marcos, H. J. A.; Croxatto, J. O.; Sande, P H.; Campanelli, J.; Jaliffa, C. O.; Benozzi, J.; Rosentein, R. E. Exp. Eye Res. 2005, 81, 71-80.

41. Shareef, S. R.; Garcia-Valenzuela, E.; Salierno, A.; Walsh, J.; Sharma, S. C. Exp. Eye Res. 1995, 61, 379-382.

42. Reitsamer, H. A.; Kiel, J. W; Harrison, J. M.; Ransom, N. L.; McKinnon, S. J. Exp. Eye Res. 2004, 78, 799-804.

43. Avila, M. Y; Stone, R. A.; Civan, M. M. Invest. Ophthalmol. Vis. Res. 2002, 43, 3021-3026.

44. Stokely, M. E.; Brady, S. T; Yorio, T Invest Ophthalmol. Vs. Sci. 2002, 43, 3223-3230.

45. Crawford, M. J.; Krishnamoorthy, R. R.; Rudick, L. V; Collier, R. J.; Kapin, M.; Agarwal, B. B.; Al-Ubaidi, M. R.; Agarwal, N. Biochem. Biophys. Res. Commun. 2001, 281, 1304-1312.

47. Verkman, A. S. Exp. Eye Res. 2003, 76, 137-143.

48. Agarwal, N.; Martin, E.; Krishnamoorthy, R. R.; Landers, R.; Wen, R.; Krueger, S.; Kapin, M. A.; Collier, R. J. Exp. Eye Res. 2002, 74, 445-453.

49. D'Cruz, P M.; Yasumura, D.; Weir, J.; Matthes, M. T; Abderrahim, H.; LaVail, M. M.; Vollrath, D. Hum. Mol. Genet. 2000, 9, 645-651.

50. Machida, S.; Kondo, M.; Jamison, J. A.; Khan, N. W; Kononen, L. T; Sugawara, T; Bush, R. A.; Sieving, P. A. Invest. Ophthal. Vis. Sci. 2000, 41, 3200-3209.

51. Fauser, S . ; Luberichs, J . ; Schuttauf, F Surv. Ophthalmol 2002, 47, 357-367 .

52. Ambati, J.; Anand, A.; Fernandez, S.; Sakurai, E.; Lynn, B. C.; Kuziel, W A.; Rollins, B. J.; Ambati, B. K. Nat. Med. 2003, 9, 1390-1397.

53. Ambati, J.; Ambati, B. K.; Yoo, S. H.; Ianchulev, S.; Adamis, A. P Surv. Ophthalmol. 2003, 48, 257-293.

54. Pulido, J. S.; Sanders, D.; Klingel, R. Can. J. Ophthalmol. 2005, 40, 332-340.

55. Melnikova, I. Nat. Rev. Drug Disc. 2005, 4, 711-712.

56. Koevary, S. B. Curr. Drug Metab. 2003, 4, 213-222.

57. Aizu, Y; Katayama, H.; Takahama, S.; Hu, J.; Nakagawa, H.; Oyanagi, K. Neuroreport 2003, 14, 2067-2071.

58. Lambiase, A.; Tirassa, P; Micera, A.; Aloe, L.; Bonini, S. Invest. Ophthalmol. Vis. Sci. 2005, 46, 3800-3806.

59. Takahashi, K.; Saishin, Y; Mori, K.; Ando, A.; Yamamoto, S.; Oshima, Y; Nambu, H.; Melia, M. B.; Bingaman, D. P; Campochiaro, P A. Invest. Ophthalmol. Vs. Sci. 2003, 44, 409-415.

60. Ke, T L.; Graff, G.; Spellman, J. M.; Yanni, J. M. Inflammation 2000, 24, 371-384.

61. Woodward, D. F; Krauss, A. H.-P; Chen, J.; Lai, R. K.; Spada, C. S.; Burke, R. M.; Andrews, S. W; Shi, L.; Liang, Y; Kedzie, K. M. et al. Surv. Ophthalmol. 2001, 45, S337-S345.

62. Hellberg, M. R.; Ke, T-L.; Haggard, K.; Klimko, P. G.; Dean, T. R.; Graff, G. J. Ocular Pharmacol. Ther. 2003, 19, 97-103.

63. Toyran, S.; Liu, Y; Sigha, S.; Shan, S.; Cho, M. R.; Gordon, R. J.; Edward, D. P Exp. Eye Res. 2005, 81, 298-305.

64. Age-Related Eye Disease Study Research Group Report 8. Arch. Ophthalmol. 2001, 119, 1417-1436.

65. Gaynes, B. I. Arch. Ophthalmol. 2003, 121, 416-417.

66. Azab, M.; Boyer, D. S.; Bressler, N. M.; Bressler, S. B.; Cihelkova, I.; Hao, Y; Immonen, I.; Lim, J. I.; Menchini, U.; Naor, J. et al. Arch. Opthalmol 2005, 123, 448-457.

67. Gragoudas, E. S.; Adamis, A. P.; Cunningham, E. T, Jr.; Feinsod, M.; Guyer, D. R. N. Engl. J. Med. 2004, 351, 2805-2816.

68. Adamis, A. P; Shima, D. T. Retina 2005, 25, 111-118.

69. Storkebaum, E.; Lambrechts, D.; Carmeliet, P. Bioessays 2004, 26, 943-954.

70. Syed, I. S.; Sanborn, T A.; Rosengart, T K. Cardiology 2004, 101, 131-143.

71. Tian, B.; Kaufman, P L. Exp. Eye Res. 2005, 80, 215-225.

72. Zhang, M.; Rao, P V Invest. Ophthalmol. Vis. Sci. 2005, 46, E-Abst. 1351.

73. Pintor, J. Curr. Opin. Invest. Drugs 2005, 6, 76-80.

74. Campana, G.; Bucolo, C.; Murari, G.; Spampinato, S. J. Pharmacol. Expt. Ther. 2002, 303, 1086-1094.

75. Wang, R.-F; Podos, S. M.; Mittag, T W; Yokoyoma, T Exp. Eye Res. 2005, 80, 629-632.

76. Chidlow, G.; Cupido, A.; Melena, J.; Osborne, N. N. Curr. Eye Res. 2001, 23, 144-153.

77. Chu, E.; Socci, R.; Chu, T. C. J. Ocular Pharmacol. Ther. 2004, 20, 15-23.

78. Pang, I.-H.; Moll, H.; McLaughlin, M. A.; Knepper, P A.; DeSantis, L.; Epstein, D. L.; Clark, A. C. Exp. Eye Res. 2001, 73, 815-825.

79. Chein, F. Y.; Wang, R.-F.; Mittag, T. W.; Podos, S. M. Arch. Ophthalmol. 2003, 121, 87-90.

80. Millar, J. C.; Shahidullah, M.; Wilson, W S. J. Ocular Pharmacol. Ther. 1997, 13, 1-11.

81. Hellberg, M. R.; McLaughlin, M. A.; Sharif, N. A.; DeSantis, L.; Dean, T. R.; Kyba, E. P; Bishop, J. E.; Klimko, P G.; Zinke, P W; Selliah, R. D. et al. Surv. Ophthalmol 2002, 47, S13-S33.

82. Epstein, D. L.; Roberts, B. C.; Skinner, L. L. Invest. Ophthalmol. Vis. Res. 1997, 38, 1526-1534.

83. Woldemussie, E.; Ruiz, G.; Wijono, M.; Wheeler, L. A. Invest. Ophthalmol. Vis. Sci. 2001, 42, 2849-2855.

84. Osborne, N. N.; Cazevieille, C.; Carvalho, A. L.; Larsen, A. K.; DeSantis, L. Brain Res. 1997, 751, 113-123.

85. Hare, W.; Woldemussie, E.; Lai, R. K.; Ton, H.; Ruiz, G.; Chun, T.; Wheeler, L. Invest. Ophthalmol. Vis. Sci. 2004, 45, 2625-2639.

86. Speicher, M. A.; Danis, R. P; Criswell, M.; Pratt, L. Expert Opin. Emerg. Drug 2003, 8, 239-250.

87. Aiello, L. P. Surv Ophthalmol. 2002, 47, S263-S269.

88. Clark, A. C.; Bingaman, D. P.; Kapin, M. A. Expert Opin. Ther. Patents 2000, 10, 427-448.

89. Thanos, C.; Emerich, D. Expert Opin. Biol. Ther. 2005, 5, 1443-1452.

90. Mukherjee, P K.; Marcheselli, V L.; Serhan, C. N.; Bazan, N. G. Proc. Natl. Acad. Sci. USA 2004, 101, 8491-8496.

91. Markomichelakis, N. N.; Theodossiadis, P. G.; Sfikakis, P. P Am. J. Ophthalmol. 2005, 139, 537-540.

92. Arnhold, S.; Klein, H.; Semkova, I.; Addicks, K.; Schraermeyer, U. Invest. Ophthalmol. Vis. Sci. 2004, 45, 4251-4255.

93. Bielroy, L.; Lien, K. W; Bigelsen, S. Drugs 2005, 65, 215-228.

94. Yanni, J. M.; Sharif, N. A.; Gamache, D. A.; Miller, S. T; Weimer, L. K.; Spellman, J. M. Acta Ophthalmol. Scand. 1999, 77, 33-37.

95. Stern, M. E.; Pflugfelder, S. C. Ocular Surface 2004, 2, 124-130.

96. McNatt, L. G.; Weimer, L.; Yanni, J.; Clark, A. C. J. Ocular Pharmacol. Ther. 1999, 15, 413-423.

97. Gamache, D. A.; Wei, Z.; Weimer, L. K.; Miller, S. T.; Spellman, J. M.; Yanni, J. M. J. Ocular Pharmacol. Ther. 2002, 18, 349-361.

98. BenEzra, D. P.; Griffin, B. W; Maftzir, G.; Sharif, N. A.; Clark, A. F Invest. Ophthalmol. Vis. Sci. 1997, 38, 1954-1962.

99. Schlech, B. A.; Blondeau, J. Surv. Ophthalmol. 2005, 50, S64-S67. 100. Oshitari, T; Brown, D.; Roy, S. Exp. Eye Res. 2005, 81, 32-37.

Biographies

NajA Sharif was educated and trained in England. He received his PhD in neuropharmacology (1982) from the University of Southampton (UK) and conducted postdoctoral work at the University of Maryland and at University of Nottingham (UK). Dr Sharif was a Staff Scientist at Parke-Davis Research Unit (Cambridge, UK) and at Syntex Research (Palo Alto, CA), and a Group Leader at Synaptic Pharmaceutical Corp (NJ). He joined Alcon Laboratories in 1992 and is a Director and Head of Pharmacology. Dr Sharif has been involved in pharmacological drug discovery research for the last 20 years, publishing over 150 papers/book chapters and editing two scientific books. Dr Sharif has filed numerous Memoranda of Invention and has authored numerous patent applications. Dr Sharif is on the Editorial Boards of several journals and reviews manuscripts for leading pharmacology and ocular journals. Dr Sharif is an Adjunct Professor at the University of North Texas (UNT) and at the University of Houston.

Peter Klimko was born in Detroit, Michigan, in 1965. He obtained his BSc degree in chemistry from Ohio State University in Columbus, Ohio, in 1987 and his PhD in synthetic organic chemistry from Texas A&M University in 1992 under the direction of Professor Daniel Singleton. After postdoctoral studies with Professor Charles Swindell at Bryn Mawr College, investigating the development of an efficient synthetic route to taxane diterpenes, Dr Klimko started at Alcon Laboratories in 1993 as a medicinal chemist. His research interests have included the exploration of prostaglandin SAR with respect to lowering intraocular pressure and the effect of arachidonic acid metabolites on dry eye symptoms.

© 2007 Elsevier Ltd. All Rights Reserved Comprehensive Medicinal Chemistry II

No part of this publication may be reproduced, stored in any retrieval system or transmitted ISBN (set): 0-08-044513-6 in any form by any means electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers ISBN (Volume 6) 0-08-044519-5; pp. 297-320

Was this article helpful?

0 0
Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment