Article

Neural degeneration in the retina of the streptozotocin-induced type 1 diabetes model.

Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan.
Experimental Diabetes Research (Impact Factor: 3.54). 01/2011; 2011:108328. DOI: 10.1155/2011/108328
Source: PubMed

ABSTRACT Diabetic retinopathy, a vision-threatening disease, has been regarded as a vascular disorder. However, impaired oscillatory potentials (OPs) in the electroretinogram (ERG) and visual dysfunction are recorded before severe vascular lesions appear. Here, we review the molecular mechanisms underlying the retinal neural degeneration observed in the streptozotocin-(STZ-) induced type 1 diabetes model. The renin-angiotensin system (RAS) and reactive oxygen species (ROS) both cause OP impairment and reduced levels of synaptophysin, a synaptic vesicle protein for neurotransmitter release, most likely through excessive protein degradation by the ubiquitin-proteasome system. ROS also decrease brain-derived neurotrophic factor (BDNF) and inner retinal neuronal cells. The influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively, are potential candidates for neuroprotective and preventive therapies to improve the visual prognosis.

0 Bookmarks
 · 
124 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Retinal neurodegeneration is a key component of diabetic retinopathy (DR), although the detailed neuronal damage remains ill-defined. Recent evidence suggests that in addition to amacrine and ganglion cell, diabetes may also impact on other retinal neurons. In this study, we examined retinal degenerative changes in Ins2Akita diabetic mice. In scotopic electroretinograms (ERG), b-wave and oscillatory potentials were severely impaired in 9-month old Ins2Akita mice. Despite no obvious pathology in fundoscopic examination, optical coherence tomography (OCT) revealed a progressive thinning of the retina from 3 months onwards. Cone but not rod photoreceptor loss was observed in 3-month-old diabetic mice. Severe impairment of synaptic connectivity at the outer plexiform layer (OPL) was detected in 9-month old Ins2Akita mice. Specifically, photoreceptor presynaptic ribbons were reduced by 25% and postsynaptic boutons by 70%, although the density of horizontal, rod- and cone-bipolar cells remained similar to non-diabetic controls. Significant reductions in GABAergic and glycinergic amacrine cells and Brn3a+ retinal ganglion cells were also observed in 9-month old Ins2Akita mice. In conclusion, the Ins2Akita mouse develops cone photoreceptor degeneration and the impairment of synaptic connectivity at the OPL, predominately resulting from the loss of postsynaptic terminal boutons. Our findings suggest that the Ins2Akita mouse is a good model to study diabetic retinal neuropathy.
    PLoS ONE 05/2014; 9(5):e97970. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative process exacerbated by several risk factors including impaired glucose metabolism in the brain that could cause molecular and neurochemical alterations in cognitive regions such as the hippocampus (Hp). Consequently, this process could cause neuronal morphological changes, however, the mechanism remains elusive. We induced chronic hyperglycemia after streptozotocin (STZ) administration. Then, we examined spatial learning and memory using the Morris water maze test and evaluated neuronal morphological changes using the Golgi–Cox stain procedure in hyperglycemic rats that received a Aβ25‐35 unilateral injection into the Hp. Our results demonstrate that STZ combined with Aβ25‐35 induced significant deficits in the spatial memory. In addition, we observed a significant reduction in the number of dendritic spines of pyramidal neurons in the dorsal Hp of rats with STZ plus Aβ25‐35. In conclusion, the reduced spine density of pyramidal neurons in the CA1 dorsal Hp could produce the spatial memory deficit observed in these animals. These results suggest that hyperglycemia can trigger Aß‐induced neurodegeneration and thus the appearance of AD symptoms would be accelerated. Synapse, 2014. © 2014 Wiley Periodicals, Inc.
    Synapse 07/2014; 68(12). · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic retinopathy is the major ocular complication associated with diabetes, and represents the leading cause of legal blindness in the working-age population of developed countries. Although classically diagnosed based on abnormalities of the retinal microvasculature, diabetic retinopathy is now widely recognized as a neurovascular disease. While all patients with diabetes are at increased risk for eye disease including diabetic retinopathy, proactive measures, and timely intervention can prevent or delay subsequent vision loss. Systemic management of diabetes by combined control of glycemia, blood pressure, and serum lipid levels remains the most important method of preventing diabetic retinopathy onset and progression. Once detected, surgical and medical interventions including photocoagulation, vitrectomy, and intravitral drug injection can help preserve vision. However, the need for improved detection methods and therapies that will allow earlier diagnosis and treatment remains apparent. This review summarizes current techniques for the prevention and intervention for diabetic retinopathy, and examines ongoing developments in the search for new endpoints and therapies as they apply to preventing vision loss associated with diabetes.
    US ophthalmic review. 01/2014; 7(1):54-58.

Full-text (2 Sources)

Download
16 Downloads
Available from
Jul 10, 2014