Strategies for blocking angiogenesis in diabetic retinopathy:: from basic science to clinical practice

被引:40
作者
Hernandez, Cristina [1 ]
Simo, Rafael [1 ]
机构
[1] Hosp Univ Vall Hebron, Diabet & Metab Res Unit, Div Endocrinol, Barcelona 08035, Spain
关键词
angiogenic factors; antiangiogenic factors; diabetic retinopathy; gene therapy; protein kinase C inhibitors; somatostatin; stem cell therapy; vascular endothelial growth factor; vitreous fluid;
D O I
10.1517/13543784.16.8.1209
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Proliferative diabetic retinopathy (PDR) demands both more effective and less expensive biologically based treatments. Our understanding of the pathophysiology of the disease is increasing as new biochemical pathways are identified. Most reports emphasize proangiogenic stimuli, with the natural inhibitory elements receiving little attention. There are two therapeutic strategies for blocking retinal angiogenesis in PDR: systemic drug administration (protein kinase C inhibitors and somatostatin analogs) or local therapies (anti-vascular endothelial growth factor strategies, anti-inflammatory agents, gene therapy and stem cell therapy). This review mainly focuses on the role of local therapies, especially intravitreous delivery, in the management of PDR. The potential for adverse effect are also discussed. The availabilitV of these new strategies or the combination of them will not only be beneficial in treating PDR but may also result in a shift towards treating earlier stages of diabetic retinopathy, thus easing the burden of this devastating disease.
引用
收藏
页码:1209 / 1226
页数:18
相关论文
共 175 条
[1]   Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy [J].
Abraham, Prema ;
Adelman, Ron A. ;
Alfaro, Daniel Virgil, III ;
Anand, Rajiv ;
Antoszyk, Andrew ;
Bergsma, Donald ;
Hartnett, Mary Elizabeth ;
Brucker, Alexander J. ;
Carr, Tyree ;
Casey, Raynor C. ;
Rubino, John ;
Chandler, Thomas W. ;
Charles, Steven ;
Chaudhry, Nauman ;
Combs, James ;
Doft, Bernard ;
Young, Lucy H. Y. ;
Drouilhet, John H. ;
Dugel, Pravin U. ;
Feman, Stephen S. ;
Finkelstein, Daniel ;
Foster, Robert E. ;
Petersen, Michael R. ;
Fox, Gregory ;
Garretson, Bruce ;
Gieser, Jon P. ;
Gentile, Ronald C. ;
Giovinazzo, Vincent ;
Glazer, Louis ;
Goodart, Roy A. ;
Gottlieb, Justin ;
Greven, Craig ;
Grizzard, William S. ;
Hainsworth, Dean P. ;
Halperin, Lawrence ;
Heier, Jeffrey S. ;
Jackson, William ;
Kubacki, Joseph J. ;
Kanter, Eric D. ;
Keyser, Bruce ;
Kingsley, Ronald ;
Ko, Paula ;
Kokame, Gregg T. ;
Kuppermann, Baruch ;
Lambert, H. Michael ;
Lewis, Hilel ;
Lewis, Richard Alan ;
Marcus, Dennis ;
Nussbaum, Julian ;
Maturi, Raj K. .
OPHTHALMOLOGY, 2006, 113 (12) :2221-2230
[2]   Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals [J].
Adamis, AP ;
Altaweel, M ;
Bressler, NM ;
Cunningham, ET ;
Davis, MD ;
Goldbaum, M ;
Gonzales, C ;
Guyer, DR ;
Katz, B ;
Patel, M .
OPHTHALMOLOGY, 2006, 113 (01) :23-28
[3]   Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate [J].
Adamis, AP ;
Shima, DT ;
Tolentino, MJ ;
Gragoudas, ES ;
Ferrara, N ;
Folkman, J ;
DAmore, PA ;
Miller, JW .
ARCHIVES OF OPHTHALMOLOGY, 1996, 114 (01) :66-71
[4]   Inhibition of PKC β by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients [J].
Aiello, LP ;
Clermont, A ;
Arora, V ;
Davis, MD ;
Sheetz, MJ ;
Bursell, SE .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (01) :86-92
[5]   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 [J].
Aiello, LP ;
Bursell, SE ;
Clermont, A ;
Duh, E ;
Ishii, H ;
Takagi, C ;
Mori, F ;
Ciulla, TA ;
Ways, K ;
Jirousek, M ;
Smith, LEH ;
King, GL .
DIABETES, 1997, 46 (09) :1473-1480
[6]  
Aiello LP, 2005, DIABETES, V54, P2188
[7]   SUPPRESSION OF RETINAL NEOVASCULARIZATION IN-VIVO BY INHIBITION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) USING SOLUBLE VEGF-RECEPTOR CHIMERIC PROTEINS [J].
AIELLO, LP ;
PIERCE, EA ;
FOLEY, ED ;
TAKAGI, H ;
CHEN, H ;
RIDDLE, L ;
FERRARA, N ;
KING, GL ;
SMITH, LEH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (23) :10457-10461
[8]   The chemokine SDF-1 is a chemoattractant for human CD34(+) hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34(+) progenitors to peripheral blood [J].
Aiuti, A ;
Webb, IJ ;
Bleul, C ;
Springer, T ;
GutierrezRamos, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (01) :111-120
[9]  
Amin RH, 1997, INVEST OPHTH VIS SCI, V38, P36
[10]   A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus [J].
Anand, V ;
Duffy, B ;
Yang, ZX ;
Dejneka, NS ;
Maguire, AM ;
Bennett, J .
MOLECULAR THERAPY, 2002, 5 (02) :125-132