Characterization of a mouse model of hyperglycemia and retinal neovascularization.
One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors--hyperglycemia and vascular endothelial growth factor--interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/-) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema.
Rakoczy
Elizabeth P
EP
Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, Australia. rakoczy@cyllene.uwa.edu.au
Ali Rahman
Ireni S
IS
Binz
Nicolette
N
Li
Cai-Rui
CR
Vagaja
Nermina N
NN
de Pinho
Marisa
M
Lai
Chooi-May
CM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004195:Disease Models, Animal; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000473:pathology / Q000503:physiopathology*; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001786:Blood Glucose; D042461:Vascular Endothelial Growth Factor A