The Ins2^AkitaMouse as a Model of Early Retinal Complications in Diabetes

Abstract

The retinas of heterozygous male Ins2(Akita) mice exhibit vascular, neural, and glial abnormalities generally consistent with clinical observations and other animal models of diabetes. In light of the relatively early, spontaneous onset of the disease and the popularity of the C57BL/6J inbred strain as a background for the generation and study of other genetic alterations, combining the Ins2(Akita) mutation with other engineered mutations will be of great use for studying the molecular basis of retinal complications of diabetes.

Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes

“…The apparent lack of cell loss from the GCL of diabetic WT (C57BL/6J) mice is consistent with prior studies by us and others [33,34], but is in contrast to another report using the same strain of mouse, where a 20% to 25% loss of cells in the GCL was observed after only 14 weeks of diabetes [35]. A 23% loss of cell bodies in the GCL from another mouse strain (Ins2 Akita mice) has been detected at 22 weeks of diabetes [36].…”

Is neuronal dysfunction an early sign of diabetic retinopathy? Microperimetry and Spectral Domain Optical Coherence Tomography (SD-OCT) Study in individuals with diabetes, but no diabetic retinopathy

“…18 Sufficient evidence also comes from the animal studies that thickness of the inner retinal layers decreases in diabetic condition, indicating early neurodegeneration. 19,20 Although apoptosis in the retinal capillary pericytes is known to cause the early microvascular changes seen in diabetic retinopathy, 21 gradual loss of neurons resulting from ganglion cell atrophy and degeneration of the inner nuclear and inner plexiform layers in diabetics has been accepted as an evidence for the early neurodegeneration occurring in diabetic retinopathy. 22 What remains to be proven is the sequence of events, that is, whether the apoptotic neuronal cell changes precede the vascular damage, or vice versa.…”

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

“…Neurotoxicity associated with excitatory amino acids was reported to be mediated to a large extent through the activation of NMDA receptors (Romano et al, 1995;Vorwerk et al, 1996). In the context of diabetes, the increase of NR1 subunit expression and of retinal glutamate content may therefore contribute to the retinal neuronal loss observed in diabetes (Aizu et al, 2002;Barber et al, 2005Barber et al, , 1998Martin et al, 2004;Park et al, 2003;Santiago et al, 2007). However, within the complex regulation of glutamate signaling and metabolism in the retina, several mechanisms may counteract the damaging effect brought upon by increased NR1 levels.…”