Wednesday, June 01, 2016

In the retina, diabetes damages nerves before it damages blood vessels. 
    Diabetes is a major risk factor for severe vision loss and blindness. A condition known as retinal diabetic neuropathy causes visual impairment through the degeneration of small nerves (neurons) in light-sensitive tissue called the retina, which lines the back of the eye. By combining evidence from human patients and mouse models, researchers from the Wynn Institute for Vision Research at the University of Iowa and the Fraternal Order of Eagles Diabetes Center, Drs. Elliott Sohn and Michael Abramoff as well as collaborators from the University of Amsterdam, show that retinal diabetic neuropathy causes progressive damage to the nerve cells in the retina before any signs of damage to the blood vessels in the retina, in contrast to widely held beliefs. To assess retinal damage, the authors used an imaging technique called optical coherence tomography in addition to microscopy. In a group of 45 patients with type 1 diabetes, the neural layers in the retina became progressively thinner over a four-year period. Moreover, these neural layers were thinner in six donor eyes from deceased diabetic individuals compared with non-diabetic controls, even though the retinal capillary density was not different between the two groups. Similarly, two mouse models of type 1 and type 2 diabetes showed significant, progressive thinning of the two tissue layers, but no vascular abnormalities compared with non-diabetic control mice. Taken together, the results suggest that retinal diabetic neuropathy precedes the vascular changes caused by diabetes. The findings may lead to the development of much-needed treatment options for patients with retinal diabetic neuropathy and potentially for diabetic retinopathy. It may also mean that screening for nerve damage in the eye should become an important part of screening for diabetes induced retinal disease. These findings were recently published in the scientific journal Proceedings of the National Academy of Sciences.

Neuroretinal hypoxic signaling in a new preclinical mouse model for proliferative diabetic retinopathy
    In addition, a second research team from the University of Iowa conducted a study on diabetic retinopathy. Thus far, it is not been possible to create a mouse model to study proliferative diabetic retinopathy, one of the major ways in which diabetes leads to blindness. A research team from the University of Iowa (Drs. Mahajan and Alexander Bassuk) and Columbia (Dr. Stephen Tsang) has made a major advance in diabetic retinopathy. Based on human vitreous (eye fluid) samples, the team identified hypoxia inducible factor in the vitreous of patients with proliferative diabetic retinopathy. Using mouse genetics, the research team then tricked photoreceptors in the retina into "overexpressing" this protein, mimicking cell specific hypoxia.

    The mouse eyes developed a striking phenotype identical to the human disease, with iris neovascularization (new blood vessel growth), cataract, vitreous hemorrhage, tractional retinal detachment, retinal neovascularization, and capillary loss. This new model will now allow investigations into therapeutic approaches to diabetic retinopathy.

    These examples of research breakthroughs by FOEDRC members will lead to more focused, effective, and improved preventative treatments that may ultimately prevent retinopathy and blindness in people with diabetes.