Retinal Angiogenesis in the Ins2^AkitaMouse Model of Diabetic Retinopathy

Abstract

These data indicate that the Ins2(Akita) mouse is a good model for later-onset DR, modeling both early and some late disease signs. Furthermore, this work suggests that this model may be suitable for testing and development of targeted DR therapies.

Oxidative stress modulates the expression of VEGF isoforms in the diabetic retina

“…Previous studies with the Ins2 Akita mice have shown a similar trend concerning pro-and anti-angiogenic factors in the retina [22]. These authors did not detect significant differences at 6-months of age but found an imbalance between the expression of VEGF and PEDF in the retinas of 9-months old diabetic mice [22]. It is suggested that the loss of anti-angiogenic factors in the retina might occur at earlier stages of the disease and it might be an event that precedes the overexpression of angiogenic factors.…”

“…In the present study, the expression of VEGF was virtually unchanged in the retina of 6-month old diabetic mice while the expression of VEGF 165 b was highly reduced, comparing with the normoglycaemic mice. Previous studies with the Ins2 Akita mice have shown a similar trend concerning pro-and anti-angiogenic factors in the retina [22]. These authors did not detect significant differences at 6-months of age but found an imbalance between the expression of VEGF and PEDF in the retinas of 9-months old diabetic mice [22].…”

“…Akita mouse, a model extensively used for the study of diabetes and diabetes-associated complications, shows evidences of hyperglycemia approximately at 4 weeks of age and retinal complications around 12 weeks after the onset of hyperglycemia [20][21][22]. In the present study it was used retinal tissue collected from 6-months old mice, a time-point where the diabetic mice demonstrate features of retinal disease [21].…”

Bowman lecture on the role of inflammation in degenerative disease of the eye

“…In experimental models, similar changes are also seen except for neovascularisation which has never been observed. (Recently it has been reported (Han et al 46 ) that the Akita mouse model of hyperglycaemia develops intraretinal neovascularisation, similar to the intraretinal microvascular abnormalities characteristic of severe diabetic retinopathy in humans. )…”

Animal Models of Diabetic Retinopathy

“…Disease onset in this model is at 8 weeks, with an increase in retinal vascular permeability and reactive gliosis. Disease progression continues up to 8 months of age, with a reduction in axons and dendrites of RGCs by 12 weeks, an increase in acellular capillaries at 36 weeks, and an increase in leukocytes in the vascular wall, as a result of inflammation [101,102]. Additionally, a decreased number of cholinergic and dopaminergic amacrine cells [103] is also observed leading to a reduction in the thickness of the IPL and INL [101,104].…”