Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:

Ординатура / Офтальмология / Английские материалы / Retinal and Choroidal Angiogenesis_Penn_2008

.pdf
Скачиваний:
0
Добавлен:
28.03.2026
Размер:
10.34 Mб
Скачать

498

D. P. Bingaman et al.

147.Y. Oshima, H. Sakaguchi, F. Gomi and Y. Tano, Regression of iris neovascularization after intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy, Am. J. Ophthalmol. 142 (1), 155-158 (2006).

148.S. Grisanti, S. Biester, S. Peters, O. Tatar, F. Ziemssen and K. U. Bartz-Schmidt, Intracameral bevacizumab for iris rubeosis, Am. J. Ophthalmol. 142 (1), 158-160 (2006).

149.C. Wulff, H. Wilson, S. J. Wiegand, J. S. Rudge and H. M. Fraser, Prevention of thecal angiogenesis, antral follicular growth, and ovulation in the primate by treatment with vascular endothelial growth factor Trap R1R2, Endocrinology 143 (7), 2797-2807 (2002).

150.J. Cao, H. Song, Y. Liu, R. A. Renard, I. B. Lobov, N. Papadopoulos, J. S. Rudge,

D.Hylton, G. D. Yancopoulos and S. J. Wiegand, Intravitreal Administration of VEGF Trap Suppresses Vascular Leak in the Retinas of Diabetic Rats, Invest. Ophthalmol. Vis. Sci. 47 1745 (2006).

151.R. A. Renard, I. B. Lobov, Y. Liu, J. Cao, K. D. Anderson, N. J. Papadopoulos,

J.S. Rudge, G. D. Yancopoulos and S. J. Wiegand, Intravitreal Administration of VEGF Trap Inhibits Pathological Retinal Neovascularization in a Mouse Model of Oxygen Induced Retinopathy, Invest. Ophthalmol. Vis. Sci. 47 1750 (2006).

152.E. Zimmer, B. J. Christian, P. E. Miller, M. T. Nork, J. N. VerHoeve, C. J. Murphy,

J.M. Miller, R. A. Leedle, J. Lesniak and E. Bentley, Safety Evaluation of Intravitreal Administration of VEGF Trap in Cynomolgus Monkeys for 13 Weeks, Invest. Ophthalmol. Vis. Sci. 47 1751 (2006).

153.E. Furfine, A. Coppil, E. Koehler-Stec, E. Zimmer, W. Tu and C. Struble, Pharmacokinetics and Ocular Tissue Penetration of VEGF Trap After Intravitreal Injections in Rabbits, Invest. Ophthalmol. Vis. Sci. 47 1430 (2006).

154.S. J. Wiegand, R. Dubielzig, E. P. Zimmer, T. M. Nork, P. E. Miller, B. J. Christian,

J.Cao, J. Cedarbaum and G. D. Yancopoulos, Histologic Evaluation of Laser-Induced Choroidal Neovascularization (CNV) in Primates Receiving Intravitreal Injections of VEGF Trap: Correlation With Fluorescein Angiography, Invest. Ophthalmol. Vis. Sci. 47 2188 (2006).

155.Q. D. Nguyen, S. M. Shah, G. Hafiz, E. Quinlan, J. Sung, K. Chu, J. M. Cedarbaum and

P.A. Campochiaro, A phase I trial of an IV-administered vascular endothelial growth factor trap for treatment in patients with choroidal neovascularization due to age-related macular degeneration, Ophthalmology 113 (9), 1522 e1521-1522 e1514 (2006).

156.S. M. Shah, Q. D. Nguyen, S. Harriprisad, K. Chu, N. Holekamp, J. Buskey, D. Nadler,

J.Cederbaum and P. A. Campochiaro, A Double-Masked, Placebo-Controlled, Safety, and Tolerability Study of Intravenous VEGF Trap in Patients With Diabetic Macular Edema, Invest. Ophthalmol. Vis. Sci. 47 3850 (2006).

157.Q. D. Nguyen, S. M. Shah, D. Browning, P. Sonkin, H. Hudson, K. Chu, K. Rich,

A.Lucas, J. Cedarbaum and P. A. Campochiaro, Results of a Phase I, Dose-Escalation, Safety, Tolerability, and Bioactivity Study of Intravitreous VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration, Invest. Ophthalmol. Vis. Sci. 47 2144 (2006).

158.T. Hunter, Signaling--2000 and beyond, Cell 100 (1), 113-127 (2000).

159.http://www.cellsignal.com/retail/.

160.G. Manning, D. B. Whyte, R. Martinez, T. Hunter and S. Sudarsanam, The protein kinase complement of the human genome, Science 298 (5600), 1912-1934 (2002).

161.D. R. Robinson, Y. M. Wu and S. F. Lin, The protein tyrosine kinase family of the human genome, Oncogene 19 (49), 5548-5557 (2000).

23. Novel Therapeutic Strategies for PSNV

499

162.C. de Vries, J. A. Escobedo, H. Ueno, K. Houck, N. Ferrara and L. T. Williams, The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor, Science 255 (5047), 989-991 (1992).

163.B. I. Terman, M. Dougher-Vermazen, M. E. Carrion, D. Dimitrov, D. C. Armellino,

D.Gospodarowicz and P. Bohlen, Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor, Biochem. Biophys. Res. Commun. 187 (3), 1579-1586 (1992).

164.J. Schlessinger, Cell signaling by receptor tyrosine kinases, Cell 103 (2), 211-225 (2000).

165.B. Millauer, S. Wizigmann-Voos, H. Schnurch, R. Martinez, N. P. Moller, W. Risau and

A.Ullrich, High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis, Cell 72 (6), 835-846 (1993).

166.T. P. Quinn, K. G. Peters, C. De Vries, N. Ferrara and L. T. Williams, Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium, Proc. Natl. Acad. Sci. USA 90 (16), 7533-7537 (1993).

167.F. Shalaby, J. Rossant, T. P. Yamaguchi, M. Gertsenstein, X. F. Wu, M. L. Breitman and A. C. Schuh, Failure of blood-island formation and vasculogenesis in Flk-1- deficient mice, Nature 376 (6535), 62-66 (1995).

168.P. Carmeliet, V. Ferreira, G. Breier, S. Pollefeyt, L. Kieckens, M. Gertsenstein, M. Fahrig, A. Vandenhoeck, K. Harpal, C. Eberhardt, C. Declercq, J. Pawling, L. Moons,

D.Collen, W. Risau and A. Nagy, Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele, Nature 380 (6573), 435-439 (1996).

169.J. Waltenberger, L. Claesson-Welsh, A. Siegbahn, M. Shibuya and C. H. Heldin, Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor, J. Biol. Chem. 269 (43), 26988-26995 (1994).

170.S. Rafii, D. Lyden, R. Benezra, K. Hattori and B. Heissig, Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?, Nat. Rev. Cancer 2 (11), 826835 (2002).

171.U. Eriksson and K. Alitalo, VEGF receptor 1 stimulates stem-cell recruitment and new hope for angiogenesis therapies, Nat. Med. 8 (8), 775-777 (2002).

172.D. Lyden, K. Hattori, S. Dias, C. Costa, P. Blaikie, L. Butros, A. Chadburn, B. Heissig,

W.Marks, L. Witte, Y. Wu, D. Hicklin, Z. Zhu, N. R. Hackett, R. G. Crystal, M. A. Moore, K. A. Hajjar, K. Manova, R. Benezra and S. Rafii, Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth, Nat. Med. 7 (11), 1194-1201 (2001).

173.M. B. Grant, W. S. May, S. Caballero, G. A. Brown, S. M. Guthrie, R. N. Mames,

B.J. Byrne, T. Vaught, P. E. Spoerri, A. B. Peck and E. W. Scott, Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization, Nat. Med. 8 (6), 607-612 (2002).

174.K. G. Csaky, J. Z. Baffi, G. A. Byrnes, J. D. Wolfe, S. C. Hilmer, J. Flippin and

S.W. Cousins, Recruitment of marrow-derived endothelial cells to experimental choroidal neovascularization by local expression of vascular endothelial growth factor, Exp. Eye Res. 78 (6), 1107-1116 (2004).

175.J. Shen, R. Samul, R. L. Silva, H. Akiyama, H. Liu, Y. Saishin, S. F. Hackett, S. Zinnen,

K.Kossen, K. Fosnaugh, C. Vargeese, A. Gomez, K. Bouhana, R. Aitchison, P. Pavco and P. A. Campochiaro, Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1, Gene Ther. (2005).

176.B. K. Ambati, M. Nozaki, N. Singh, A. Takeda, P. D. Jani, T. Suthar, R. J. Albuquerque,

E.Richter, E. Sakurai, M. T. Newcomb, M. E. Kleinman, R. B. Caldwell, Q. Lin,

Y.Ogura, A. Orecchia, D. A. Samuelson, D. W. Agnew, J. St Leger, W. R. Green,

500

D. P. Bingaman et al.

P. J. Mahasreshti, D. T. Curiel, D. Kwan, H. Marsh, S. Ikeda, L. J. Leiper,

J.M. Collinson, S. Bogdanovich, T. S. Khurana, M. Shibuya, M. E. Baldwin,

N.Ferrara, H. P. Gerber, S. De Falco, J. Witta, J. Z. Baffi, B. J. Raisler and J. Ambati, Corneal avascularity is due to soluble VEGF receptor-1, Nature 443 (7114), 993-997 (2006).

177.J. Krishnan, V. Kirkin, A. Steffen, M. Hegen, D. Weih, S. Tomarev, J. Wilting and

J.P. Sleeman, Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats, Cancer Res. 63 (3), 713-722 (2003).

178.A. Ostman and C. H. Heldin, Involvement of platelet-derived growth factor in disease: development of specific antagonists, Adv. Cancer Res. 80, 1-38 (2001).

179.L. E. Benjamin, I. Hemo and E. Keshet, A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF, Development 125 (9), 1591-1598 (1998).

180.D. Fukumura, R. Xavier, T. Sugiura, Y. Chen, E. C. Park, N. Lu, M. Selig, G. Nielsen,

T.Taksir, R. K. Jain and B. Seed, Tumor induction of VEGF promoter activity in stromal cells, Cell 94 (6), 715-725 (1998).

181.F. Ponten, Z. Ren, M. Nister, B. Westermark and J. Ponten, Epithelial-stromal interactions in basal cell cancer: the PDGF system, J. Invest. Dermatol 102 (3), 304-309 (1994).

182.M. Skobe and N. E. Fusenig, Tumorigenic conversion of immortal human keratinocytes through stromal cell activation, Proc. Natl. Acad. Sci. USA 95 (3), 1050-1055 (1998).

183.D. Wang, H. J. Huang, A. Kazlauskas and W. K. Cavenee, Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase, Cancer Res. 59 (7), 1464-1472 (1999).

184.P. Lindahl, B. R. Johansson, P. Leveen and C. Betsholtz, Pericyte loss and microaneurysm formation in PDGF-B-deficient mice, Science 277 (5323), 242-245 (1997).

185.M. Hellstrom, M. Kalen, P. Lindahl, A. Abramsson and C. Betsholtz, Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse, Development 126 (14), 3047-3055 (1999).

186.N. Reinmuth, W. Liu, Y. D. Jung, S. A. Ahmad, R. M. Shaheen, F. Fan, C. D. Bucana,

G.McMahon, G. E. Gallick and L. M. Ellis, Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival, FASEB J. 15 (7), 1239-1241 (2001).

187.D. George, Platelet-derived growth factor receptors: a therapeutic target in solid tumors, Semin. Oncol. 28 (5 Suppl 17), 27-33 (2001).

188.K. Pietras, K. Rubin, T. Sjoblom, E. Buchdunger, M. Sjoquist, C. H. Heldin and

A.Ostman, Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy, Cancer Res. 62 (19), 5476-5484 (2002).

189.J. L. Wilkinson-Berka, S. Babic, T. De Gooyer, A. W. Stitt, K. Jaworski, L. G. Ong,

D.J. Kelly and R. E. Gilbert, Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy, Am. J. Pathol. 164 (4), 1263-1273 (2004).

190.H. S. Mudhar, R. A. Pollock, C. Wang, C. D. Stiles and W. D. Richardson, PDGF and its receptors in the developing rodent retina and optic nerve, Development 118 (2), 539-552 (1993).

23. Novel Therapeutic Strategies for PSNV

501

191.T. Asahara, D. Chen, T. Takahashi, K. Fujikawa, M. Kearney, M. Magner, G. D. Yancopoulos and J. M. Isner, Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization, Circ. Res. 83 (3), 233-240 (1998).

192.A. Otani, H. Takagi, H. Oh, S. Koyama, M. Matsumura and Y. Honda, Expressions of angiopoietins and Tie2 in human choroidal neovascular membranes, Invest. Ophthalmol. Vis. Sci. 40 (9), 1912-1920 (1999).

193.H. Oh, H. Takagi, K. Suzuma, A. Otani, M. Matsumura and Y. Honda, Hypoxia and

vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells, J. Biol. Chem 274 (22), 15732-15739 (1999).

194. S. F. Hackett, H. Ozaki, R. W. Strauss, K. Wahlin, C. Suri, P. Maisonpierre,

G.Yancopoulos and P. A. Campochiaro, Angiopoietin 2 expression in the retina: upregulation during physiologic and pathologic neovascularization, J. Cell. Physiol. 184 (3), 275-284 (2000).

195.S. Sarlos, B. Rizkalla, C. J. Moravski, Z. Cao, M. E. Cooper and J. L. Wilkinson-Berka, Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin, Am. J. Pathol. 163 (3), 879-887 (2003).

196.H. P. Hammes, J. Lin, P. Wagner, Y. Feng, F. Vom Hagen, T. Krzizok, O. Renner,

G.Breier, M. Brownlee and U. Deutsch, Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy, Diabetes 53 (4), 1104-1110 (2004).

197.H. Ohashi, H. Takagi, S. Koyama, H. Oh, D. Watanabe, D. A. Antonetti, T. Matsubara,

K.Nagai, H. Arai, T. Kita and Y. Honda, Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats, Mol. Vis. 10, 608-617 (2004).

198.H. Takagi, S. Koyama, H. Seike, H. Oh, A. Otani, M. Matsumura and Y. Honda, Potential role of the angiopoietin/tie2 system in ischemia-induced retinal neovascularization, Invest. Ophthalmol. Vis. Sci. 44 (1), 393-402 (2003).

199.A. Morabito, E. De Maio, M. Di Maio, N. Normanno and F. Perrone, Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions, The Oncologist 11 (7), 753-764 (2006).

200.A. Gschwind, O. M. Fischer and A. Ullrich, The discovery of receptor tyrosine kinases: targets for cancer therapy, Nat. Rev. Cancer 4 (5), 361-370 (2004).

201.P. Traxler, G. Bold, E. Buchdunger, G. Caravatti, P. Furet, P. Manley, T. O’Reilly,

J.Wood and J. Zimmermann, Tyrosine kinase inhibitors: from rational design to clinical trials, Med. Res. Rev. 21 (6), 499-512 (2001).

202.C. Murakata, M. Kaneko, G. Gessner, T. S. Angeles, M. A. Ator, T. M. O’Kane,

B.A. McKenna, B. A. Thomas, J. R. Mathiasen, M. S. Saporito, D. Bozyczko-Coyne and R. L. Hudkins, Mixed lineage kinase activity of indolocarbazole analogues, Bioorg. Med. Chem. Lett. 12 (2), 147-150 (2002).

203.D. S. Lawrence and J. Niu, Protein kinase inhibitors: the tyrosine-specific protein kinases, Pharmacol. Ther. 77 (2), 81-114 (1998).

204.M. S. Seo, N. Kwak, H. Ozaki, H. Yamada, N. Okamoto, E. Yamada, D. Fabbro,

F.Hofmann, J. M. Wood and P. A. Campochiaro, Dramatic inhibition of retinal and choroidal neovascularization by oral administration of a kinase inhibitor, Am. J. Pathol. 154 (6), 1743-1753 (1999).

205.H. Ozaki, M. S. Seo, K. Ozaki, H. Yamada, E. Yamada, N. Okamoto, F. Hofmann,

J.M. Wood and P. A. Campochiaro, Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization, Am. J. Pathol. 156 (2), 697-707 (2000).

502

D. P. Bingaman et al.

206.F. Kinose, G. Roscilli, S. Lamartina, K. D. Anderson, F. Bonelli, S. G. Spence,

G.Ciliberto, T. F. Vogt, D. J. Holder, C. Toniatti and C. J. Thut, Inhibition of retinal and choroidal neovascularization by a novel KDR kinase inhibitor, Mol. Vis. 11 366-373 (2005).

207.P. A. Campochiaro, Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412, Invest. Ophthalmol. Vis. Sci. 45 (3), 922-931 (2004).

208.H. Mellor and P. J. Parker, The extended protein kinase C superfamily, Biochem. J. 332 (Pt 2), 281-292 (1998).

209.P. Xia, T. Inoguchi, T. S. Kern, R. L. Engerman, P. J. Oates and G. L. King, Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia, Diabetes 43 (9), 1122-1129 (1994).

210.S. E. Bursell, C. Takagi, A. C. Clermont, H. Takagi, F. Mori, H. Ishii and G. L. King, Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats, Invest. Ophthalmol. Vis. Sci. 38 (13), 2711-2720 (1997).

211.H. Ishii, D. Koya and G. L. King, Protein kinase C activation and its role in the development of vascular complications in diabetes mellitus, J. Mol. Med. 76 (1), 21-31 (1998).

212.T. Inoguchi, R. Battan, E. Handler, J. R. Sportsman, W. Heath and G. L. King, Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation, Proc. Natl. Acad. Sci. USA 89 (22), 11059-11063 (1992).

213.S. E. Bursell, A. C. Clermont, B. T. Kinsley, D. C. Simonson, L. M. Aiello and

H.A. Wolpert, Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy, Invest. Ophthalmol. Vis. Sci. 37 (5), 886-897 (1996).

214.L. P. Aiello, S. E. Bursell, A. Clermont, E. Duh, H. Ishii, C. Takagi, F. Mori,

T.A. Ciulla, K. Ways, M. Jirousek, L. E. Smith and G. L. King, Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor, Diabetes 46 (9), 1473-1480 (1997).

215.G. T. Feke, S. M. Buzney, H. Ogasawara, N. Fujio, D. G. Goger, N. P. Spack and

K.H. Gabbay, Retinal circulatory abnormalities in type 1 diabetes, Invest. Ophthalmol. Vis. Sci. 35 (7), 2968-2975 (1994).

216.R. P. Danis, D. P. Bingaman, M. Jirousek and Y. Yang, Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKCbeta inhibition with LY333531, Invest. Ophthalmol. Vis. Sci. 39 (1), 171-179 (1998).

217.A. Nonaka, J. Kiryu, A. Tsujikawa, K. Yamashiro, K. Miyamoto, H. Nishiwaki,

Y.Honda and Y. Ogura, PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats, Invest. Ophthalmol. Vis. Sci. 41 (9), 2702-2706 (2000).

218.X. Xu, Q. Zhu, X. Xia, S. Zhang, Q. Gu and D. Luo, Blood-retinal barrier breakdown induced by activation of protein kinase C via vascular endothelial growth factor in streptozotocin-induced diabetic rats, Curr. Eye Res. 28 (4), 251-256 (2004).

219.P. Xia, L. P. Aiello, H. Ishii, Z. Y. Jiang, D. J. Park, G. S. Robinson, H. Takagi,

W.P. Newsome, M. R. Jirousek and G. L. King, Characterization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms, and endothelial cell growth, J. Clin Invest. 98 (9), 2018-2026 (1996).

23. Novel Therapeutic Strategies for PSNV

503

220.K. Suzuma, N. Takahara, I. Suzuma, K. Isshiki, K. Ueki, M. Leitges, L. P. Aiello and

G.L. King, Characterization of protein kinase C beta isoform’s action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization, Proc. Natl. Acad. Sci. USA 99 (2), 721-726 (2002).

221.N. S. Harhaj, E. A. Felinski, E. B. Wolpert, J. M. Sundstrom, T. W. Gardner and

D.A. Antonetti, VEGF activation of protein kinase C stimulates occludin phosphorylation and contributes to endothelial permeability, Invest. Ophthalmol. Vis. Sci. 47 (11), 5106-5115 (2006).

222.M. R. Jirousek, J. R. Gillig, C. M. Gonzalez, W. F. Heath, J. H. McDonald, 3rd,

D.A. Neel, C. J. Rito, U. Singh, L. E. Stramm, A. Melikian Badalian, M. Baevsky,

L.M. Ballas, S. E. Hall, L. L. Winneroski and M. M. Faul, (S)-13-[(dimethylamino) methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo [3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta, J. Med. Chem. 39 (14), 2664-2671 (1996).

223.H. Ishii, M. R. Jirousek, D. Koya, C. Takagi, P. Xia, A. Clermont, S. E. Bursell,

T.S. Kern, L. M. Ballas, W. F. Heath, L. E. Stramm, E. P. Feener and G. L. King, Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor, Science 272 (5262), 728-731 (1996).

224.I. Idris, S. Gray and R. Donnelly, Protein kinase C-beta inhibition and diabetic microangiopathy: effects on endothelial permeability responses in vitro, Eur. J. Pharmacol. 485 (1-3), 141-144 (2004).

225.J. A. Beckman, A. B. Goldfine, M. B. Gordon, L. A. Garrett and M. A. Creager, Inhibition of protein kinase Cbeta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans, Circ. Res. 90 (1), 107-111 (2002).

226.The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial, Diabetes 54 (7), 2188-2197 (2005).

227.C. Strom, B. Sander, K. Klemp, L. P. Aiello, H. Lund-Andersen and M. Larsen, Effect of ruboxistaurin on blood-retinal barrier permeability in relation to severity of leakage in diabetic macular edema, Invest. Ophthalmol. Vis. Sci. 46 (10), 3855-3858 (2005).

228.PRNewswire, Lilly Announces FDA Requirement of Additional Clinical Trial Before Ruboxistaurin Could Be Approved for Treatment of Diabetic Retinopathy http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/09-29- 2006/0004442237&EDATE= September 29 (2006).

229.A. Fire, S. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver and C. C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans, Nature 391 (6669), 806-811 (1998).

230.M. K. Montgomery, S. Xu and A. Fire, RNA as a target of double-stranded RNAmediated genetic interference in Caenorhabditis elegans, Proc. Natl. Acad. Sci. USA 95 (26), 15502-15507 (1998).

231.A. J. Hamilton and D. C. Baulcombe, A species of small antisense RNA in posttranscriptional gene silencing in plants, Science 286 (5441), 950-952 (1999).

232.S. M. Elbashir, W. Lendeckel and T. Tuschl, RNA interference is mediated by 21and 22-nucleotide RNAs, Genes Dev. 15 (2), 188-200 (2001).

233.Y. Dorsett and T. Tuschl, siRNAs: applications in functional genomics and potential as therapeutics, Nat. Rev. Drug Discov. 3 (4), 318-329 (2004).

504

D. P. Bingaman et al.

234.Acuity-Pharmaceuticals, Acuity Pharmaceuticals reports positive phase II results for Bevasiranib in wet AMD, http://www.acuitypharma.com/press/release15.pdf

September 11 (2006).

235.Acuity-Pharmaceuticals, Acuity Pharmaceuticals reports positive initial phase II results for Bevasiranib (cand5) in wet AMD, http://www.acuitypharma.com/press/release13.pdf

June 1 (2006).

236.Acuity-Pharmaceuticals, Acuity Pharmaceuticals initiates phase II trial of Cand5 in wet AMD following successful completion of phase I, http://www.acuitypharma.com/ press/release9.pdf October 14 (2005).

237.M. J. Tolentino, A. J. Brucker, J. Fosnot, G. S. Ying, I. H. Wu, G. Malik, S. Wan and

S.J. Reich, Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization, Retina 24 (1), 132-138 (2004).

238.S. J. Reich, J. Fosnot, A. Kuroki, W. Tang, X. Yang, A. M. Maguire, J. Bennett and

M.J. Tolentino, Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model, Mol. Vis. 9, 210-216 (2003).

239.M. J. Tolentino, A. J. Brucker, S. Wan, S. J. Reich, J. Gordon and Y. J. Duh, Re: Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization, Retina 24 (4), 661 (2004).

240.Chemical-Business-NewsBase, Sirna Therapeutics announces results from interim analysis of Phase I single dose trial with Sirna-027 in patients with age-related macular degeneration., http://workgroups.newsedge.com/display_news.asp?doc_id=NEa0512544.8iw

May 12 (2005).

241.E. Quinlan, siRNA Directed Against VEGFR1 mRNA for AMD, Invest. Ophthalmol. Vis. Sci. 46 SIG 387 Blockade of VEGF: Lessons from Early Clinical Experiences (2005).

242.Bioworld-Today, Sirna’s RNAi Work Lands $250M Deal With Allergan By Jennifer Boggs Staff Writer., http://workgroups.newsedge.com/display_news.asp? doc_id=NEi1003678. 3ac October 03 (2005).

243.Business-Wire, Merck & Co., Inc. Announces Completion of Acquisition of Sirna Therapeutics, Inc., http://phx.corporate-ir.net/phoenix.zhtml?c=141787&p=irol- newsArticle&ID=945592&highlight= 12-29-2006 (2006).

244.Bioworld-Today, Isis, Alnylam Sign RNAi Deal; Goal To Make ‘One-Stop Shop’, http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?forceid=32320&next =bioWorldToday_article&search=1&prodID=4&htsid=13&htmax=16 March 15

(2004).

245.PR-Newswire, Alnylam Reports Progress in Strategic Alliance with Merck, http://workgroups.newsedge.com/display_news.asp?doc_id=NEp0103008.3rw January 04 (2005).

246.J. E. Poulsen, Diabetes and anterior pituitary insufficiency. Final course and postmortem study of a diabetic patient with Sheehan’s syndrome, Diabetes 15 (2), 73-77 (1966).

247.J. E. Poulsen, Recovery from retinopathy in a case of diabetes with Simmonds’ disease, Diabetes 2 (1), 7-12 (1953).

248.D. A. Adams, R. W. Rand, N. H. Roth, A. M. Dashe, R. M. Gipstein and G. Heuser, Hypophysectomy in diabetic retinopathy. The relationship between the degree of pituitary ablation and ocular response, Diabetes 23 (8), 698-707 (1974).

249.M. Grant, B. Russell, C. Fitzgerald and T. J. Merimee, Insulin-like growth factors in vitreous. Studies in control and diabetic subjects with neovascularization, Diabetes 35 (4), 416-420 (1986).

23. Novel Therapeutic Strategies for PSNV

505

250.R. Meyer-Schwickerath, A. Pfeiffer, W. F. Blum, H. Freyberger, M. Klein, C. Losche,

R.Rollmann and H. Schatz, Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects, J. Clin. Invest. 92 (6), 2620-2625 (1993).

251.R. J. Waldbillig, B. E. Jones, T. J. Schoen, P. Moshayedi, S. Heidersbach, M. S. Bitar,

F.J. van Kuijk, E. de Juan, P. Kador and G. J. Chader, Vitreal insulin-like growth factor binding proteins (IGFBPs) are increased in human and animal diabetics, Curr. Eye Res. 13 (7), 539-546 (1994).

252.M. Boulton, Z. Gregor, D. McLeod, D. Charteris, J. Jarvis-Evans, P. Moriarty,

A.Khaliq, D. Foreman, D. Allamby and B. Bardsley, Intravitreal growth factors in proliferative diabetic retinopathy: correlation with neovascular activity and glycaemic management, Br. J. Ophthalmol. 81 (3), 228-233 (1997).

253.A. Pfeiffer, J. Spranger, R. Meyer-Schwickerath and H. Schatz, Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown, Diabetes 46 Suppl 2 S26-30 (1997).

254.R. Rosenthal, H. Wohlleben, G. Malek, L. Schlichting, H. Thieme, C. Bowes Rickman and O. Strauss, Insulin-like growth factor-1 contributes to neovascularization in agerelated macular degeneration, Biochem. Biophys. Res. Commun. 323 (4), 1203-1208 (2004).

255.J. J. Kopchick and S. Okada, Growth hormone receptor antagonists: discovery and potential uses, Growth Horm. IGF Res. 11 Suppl A, S103-109 (2001).

256.H. Kitamei, M. Yokoi, M. Kase and S. Ohno, Retinal neovascularization during treatment with IGF-1 for insulin resistance syndrome, Graefes Arch. Clin. Exp. Ophthalmol. 243 (7), 715-717 (2005).

257.P. Moriarty, M. Boulton, A. Dickson and D. McLeod, Production of IGF-I and IGF binding proteins by retinal cells in vitro, Br. J. Ophthalmol. 78 (8), 638-642 (1994).

258.M. B. Grant, S. Caballero and W. J. Millard, Inhibition of IGF-I and b-FGF stimulated growth of human retinal endothelial cells by the somatostatin analogue, octreotide: a potential treatment for ocular neovascularization, Regulatory peptides 48 (1-2), 267-278 (1993).

259.M. B. Grant, R. N. Mames, C. Fitzgerald, E. A. Ellis, M. Aboufriekha and J. Guy, Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina: comparative studies with basic fibroblast growth factor, Diabetologia 36 (4), 282-291 (1993).

260.R. P. Danis and D. P. Bingaman, Insulin-like growth factor-1 retinal microangiopathy in the pig eye, Ophthalmology 104 (10), 1661-1669 (1997).

261.L. E. Smith, J. J. Kopchick, W. Chen, J. Knapp, F. Kinose, D. Daley, E. Foley,

R.G. Smith and J. M. Schaeffer, Essential role of growth hormone in ischemia-induced retinal neovascularization, Science 276 (5319), 1706-1709 (1997).

262.T. Kondo, D. Vicent, K. Suzuma, M. Yanagisawa, G. L. King, M. Holzenberger and

C.R. Kahn, Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization, J. Clin. Invest. 111 (12), 1835-1842 (2003).

263.J. Ruberte, E. Ayuso, M. Navarro, A. Carretero, V. Nacher, V. Haurigot, M. George,

C.Llombart, A. Casellas, C. Costa, A. Bosch and F. Bosch, Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease, J. Clin. Invest. 113 (8), 1149-1157 (2004).

264.R. S. Punglia, M. Lu, J. Hsu, M. Kuroki, M. J. Tolentino, K. Keough, A. P. Levy,

N.S. Levy, M. A. Goldberg, R. J. D’Amato and A. P. Adamis, Regulation of vascular

506

D. P. Bingaman et al.

endothelial growth factor expression by insulin-like growth factor I, Diabetes 46 (10), 1619-1626 (1997).

265.C. Treins, S. Giorgetti-Peraldi, J. Murdaca, M. N. Monthouel-Kartmann and E. Van Obberghen, Regulation of hypoxia-inducible factor (HIF)-1 activity and expression of HIF hydroxylases in response to insulin-like growth factor I, Molecular Endocrinology (Baltimore, MD) 19 (5), 1304-1317 (2005).

266.P. E. Spoerri, A. Afzal, S. Li Calzi, L. C. Shaw, J. Cai, H. Pan, M. Boulton and

M.B. Grant, Effects of VEGFR-1, VEGFR-2, and IGF-IR hammerhead ribozymes on glucose-mediated tight junction expression in cultured human retinal endothelial cells, Mol. Vis. 12 32-42 (2006).

267.J. Pless, From somatostatin to Sandostatin: history and chemistry, Metabolism: Clinical and Experimental 41 (9 Suppl 2), 5-6 (1992).

268.D. D. Klisovic, M. S. O’Dorisio, S. E. Katz, J. W. Sall, D. Balster, T. M. O’Dorisio,

E.Craig and M. Lubow, Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study, Invest. Ophthalmol. Vis. Sci. 42 (10), 2193-2201 (2001).

269.S. E. Katz, D. D. Klisovic, M. S. O’Dorisio, R. Lynch and M. Lubow, Expression of

somatostatin receptors 1 and 2 in human choroid plexus and arachnoid granulations: implications for idiopathic intracranial hypertension, Arch. Ophthalmol. 120 (11), 1540-1543 (2002).

270. A. Vasilaki, T. Papadaki, G. Notas, G. Kolios, N. Mastrodimou, D. Hoyer, M. Tsilimbaris, E. Kouroumalis, I. Pallikaris and K. Thermos, Effect of somatostatin on nitric oxide production in human retinal pigment epithelium cell cultures, Invest. Ophthalmol. Vis. Sci. 45 (5), 1499-1506 (2004).

271.C. Hernandez, E. Carrasco, R. Casamitjana, R. Deulofeu, J. Garcia-Arumi and R. Simo, Somatostatin molecular variants in the vitreous fluid: a comparative study between

diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects, Diabetes Care 28 (8), 1941-1947 (2005).

272. A. C. Lambooij, R. W. Kuijpers, E. G. van Lichtenauer-Kaligis, M. Kliffen, G. S. Baarsma, P. M. van Hagen and C. M. Mooy, Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration, Invest. Ophthalmol. Vis. Sci. 41 (8), 2329-2335 (2000).

273.J. W. Sall, D. D. Klisovic, M. S. O’Dorisio and S. E. Katz, Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells, Exp. Eye Res. 79 (4), 465-476 (2004).

274.Y. Bezerra, J. A. Fuselier, G. A. Peyman, H. Oner, G. Drouant and D. H. Coy, Study of inhibitory effects of an antiangiogenic somatostatin-camptothecin conjugate on laserinduced choroidal neovascularization in rats, Retina 25 (3), 345-354 (2005).

275.M. B. Grant and S. Caballero, Jr., The potential role of octreotide in the treatment of diabetic retinopathy, Treatments in Endocrinology 4 (4), 199-203 (2005).

276.M. B. Grant and S. Caballero, Somatostatin analogues as drug therapies for retinopathies, Drugs Today (Barc) 38 (11), 783-791 (2002).

277.U. Wegewitz, I. Gohring and J. Spranger, Novel approaches in the treatment of angiogenic eye disease, Curr. Pharm. Des. 11 (18), 2311-2330 (2005).

278.D. W. Zlock, F. S. Greenspan, O. H. Clark and C. B. Higgins, Octreotide therapy in advanced thyroid cancer, Thyroid 4 (4), 427-431 (1994).

279.S. L. Hyer, P. S. Sharp, R. A. Brooks, J. M. Burrin and E. M. Kohner, Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy, Acta Endocrinologica 120 (2), 187-194 (1989).

23. Novel Therapeutic Strategies for PSNV

507

280.S. L. Shumak, L. D. Grossman, E. Chew, V. Kozousek, S. R. George, W. Singer, A. G. Harris and B. Zinman, Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study, Clinical and Investigative Medicine 13 (5), 287-292 (1990).

281.B. Mallet, B. Vialettes, S. Haroche, P. Escoffier, P. Gastaut, J. P. Taubert and P. Vague, Stabilization of severe proliferative diabetic retinopathy by long-term treatment with SMS 201-995, Diabete & Metabolisme 18 (6), 438-444 (1992).

282.M. McCombe, S. Lightman, D. J. Eckland, A. M. Hamilton and S. L. Lightman, Effect of a long-acting somatostatin analogue (BIM23014) on proliferative diabetic retinopathy: a pilot study, Eye 5 (Pt 5), 569-575 (1991).

283.M. C. Hernaez-Ortega, E. Soto-Pedre and J. J. Martin, Sandostatin LAR for cystoid diabetic macular edema: a 1-year experience, Diabetes Research and Clinical Practice 64 (1), 71-72 (2004).

284.C. Kirkegaard, K. Norgaard, O. Snorgaard, T. Bek, M. Larsen and H. Lund-Andersen, Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus, Acta Endocrinologica 122 (6), 766-772 (1990).

285.K. L. Goa, M. Haria and M. I. Wilde, Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus, Drugs 53 (6), 1081-1105 (1997).

286. N. Chaturvedi, A. K. Sjolie, J. M. Stephenson, H. Abrahamian, M. Keipes,

A.Castellarin, Z. Rogulja-Pepeonik and J. H. Fuller, Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus, Lancet 351 (9095), 28-31 (1998).

287.B. Williams, Angiotensin II, VEGF, and diabetic retinopathy, Lancet 351 (9105), 837-838 (1998).

288.M. Egeblad and Z. Werb, New functions for the matrix metalloproteinases in cancer progression, Nat. Rev. Cancer 2 (3), 161-174 (2002).

289.M. A. Moses, The regulation of neovascularization of matrix metalloproteinases and their inhibitors, Stem Cells 15 (3), 180-189 (1997).

290.A. H. Baker, D. R. Edwards and G. Murphy, Metalloproteinase inhibitors: biological actions and therapeutic opportunities, J. Cell Sci. 115 (Pt 19), 3719-3727 (2002).

291.C. Takahashi, Z. Sheng, T. P. Horan, H. Kitayama, M. Maki, K. Hitomi, Y. Kitaura,

S.Takai, R. M. Sasahara, A. Horimoto, Y. Ikawa, B. J. Ratzkin, T. Arakawa and

M.Noda, Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK, Proc. Natl. Acad. Sci. USA 95 (22), 13221-13226 (1998).

292.M. M. Handsley and D. R. Edwards, Metalloproteinases and their inhibitors in tumor angiogenesis, Int. J. Cancer 115 (6), 849-860 (2005).

293.D. R. Shalinsky, J. Brekken, H. Zou, L. A. Bloom, C. D. McDermott, S. Zook,

N.M. Varki and K. Appelt, Marked antiangiogenic and antitumor efficacy of AG3340 in chemoresistant human non-small cell lung cancer tumors: single agent and combination chemotherapy studies, Clin. Cancer Res. 5 (7), 1905-1917 (1999).

294.C. Garcia, D. U. Bartsch, M. E. Rivero, M. Hagedorn, C. D. McDermott, G. Bergeron Lynn, L. Cheng, K. Appelt and W. R. Freeman, Efficacy of Prinomastat) (AG3340), a matrix metalloprotease inhibitor, in treatment of retinal neovascularization, Curr. Eye Res. 24 (1), 33-38 (2002).

295.M. H. El-Bradley, D. A. Cheresh, K. Appelt, D. U. Bartsch, D. Plummer, G. Bergeron Lynn, G. M. Severson and W. R. Freeman, Prevention of experimental laser induced