Somatostatin analogues as drug therapies for retinopathies.
Proliferative retinopathies account for the majority of cases of vision loss throughout the world. Currently accepted therapy for retinopathy consists of retinal ablation by panretinal laser photocoagulation or cryotherapy. This technique is not without deleterious effects to patients, including diminished night vision, reduced peripheral vision and loss of precise vision, decreasing visual acuity by one to two lines in magnitude. One promising area of research into pharmacotherapeutics for retinopathies, especially proliferative diabetic retinopathy, involves the use of synthetic analogues of somatostatin. The rationale for somatostatin as a therapeutic agent for retinal neovascularization is discussed. Somatostatin analogues such as octreotide have shown promise as a safe and effective treatment for severe proliferative diabetic retinopathy by blocking the local and systemic production of growth hormone and insulin-like growth factor type 1 associated with angiogenesis and endothelial cell proliferation. There are also observations suggesting an autocrine and paracrine effect of somatostatin, perhaps directly on retinal cells, which are known to express somatostatin receptors (SSTR). SSTR2 and SSTR3 are the most important receptor subtypes mediating growth hormone secretion and endothelial cell cycle arrest, retinal endothelial cell apoptosis and release of insulin. Thus, analogues that target these receptor subtypes may prove more useful. Long-acting somatostatin analogues are currently being tested for treatment of diabetic retinopathy and are, in fact, the only therapeutic alternative for patients who fail panretinal photocoagulation. Whether such a therapy may also prove effective for other retinal vascular proliferative diseases such as retinopathy of prematurity and age-related macular degeneration remains an open question that deserves attention, given our new understanding of the cellular and molecular mechanisms by which somatostatin may exert its antiangiogenic effects.
Grant
Maria B
MB
Department of Pharmacology and Therapeutics, PO Box 100267, University of Florida, 1600 SW Archer Road, Room R-5244, Gainesville, FL 32610-0267, U.S.A. grantma@pharmacology.ufl.edu
Caballero
Sergio
S
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D006728:Hormones / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000187:drug effects; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000209:etiology; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000502:physiology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D006728:Hormones; D017481:Receptors, Somatostatin; D013004:Somatostatin; D015282:Octreotide