Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease.
IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood. Here we show that normoglycemic/normoinsulinemic transgenic mice overexpressing IGF-1 in the retina developed most alterations seen in human diabetic eye disease. A paracrine effect of IGF-1 in the retina initiated vascular alterations that progressed from nonproliferative to proliferative retinopathy and retinal detachment. Eyes from 2-month-old transgenic mice showed loss of pericytes and thickening of basement membrane of retinal capillaries. In mice 6 months and older, venule dilatation, intraretinal microvascular abnormalities, and neovascularization of the retina and vitreous cavity were observed. Neovascularization was consistent with increased IGF-1 induction of VEGF expression in retinal glial cells. In addition, IGF-1 accumulated in aqueous humor, which may have caused rubeosis iridis and subsequently adhesions between the cornea and iris that hampered aqueous humor drainage and led to neovascular glaucoma. Furthermore, all transgenic mice developed cataracts. These findings suggest a role of IGF-1 in the development of ocular complications in long-term diabetes. Thus, these transgenic mice may be used to study the mechanisms that lead to diabetes eye disease and constitute an appropriate model in which to assay new therapies.
Ruberte
Jesús
J
Center of Animal Biotechnology and Gene Therapy, Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Bellaterra, Spain.
Ayuso
Eduard
E
Navarro
Marc
M
Carretero
Ana
A
Nacher
Víctor
V
Haurigot
Virginia
V
George
Mónica
M
Llombart
Cristina
C
Casellas
Alba
A
Costa
Cristina
C
Bosch
Assumpció
A
Bosch
Fatima
F
D000818:Animals; D002386:Cataract / Q000209:etiology; D003930:Diabetic Retinopathy / Q000209:etiology*; D015355:Glaucoma, Neovascular / Q000209:etiology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012160:Retina / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D005904:Glial Fibrillary Acidic Protein; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I