Experimental Diabetic Glomerulosclerosis

Bloodworth, J. M. B.; Hamwi, George J.

doi:10.2337/diab.5.1.37

Cited by 53 publications

(42 citation statements)

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“…Neuronal degeneration patterns have been observed in various animal models of diabetes, and early retinal dysfunction has been demonstrated (3,4). Postmortem studies in humans have revealed neuronal degeneration and apoptosis in retinas, mainly in the ganglion cell layer (5,6). Furthermore, use of the modern technique of spectral domain optical coherence tomography for retinal imaging (7) has shown thinning of the retinal nerve fiber (8,9) and photoreceptor layers (10) in diabetic subjects in vivo before any visible vascular lesions could be detected.…”

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Progression of Early Retinal Dysfunction in Diabetes Over Time: Results of a Long-term Prospective Clinical Study

2014

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We explored signs of retinal dysfunction over time in diabetic subjects before or early in the course of retinopathy. Patients with no, mild, or moderate retinopathy were consecutively recruited and underwent standard automated perimetry, visual acuity measurement, and fundus photography. These examinations and measurements of HbA 1c and blood pressure were repeated for up to 5 years from baseline. Visual field improvement/deterioration in diabetic subjects was evaluated using significance limits for change. Progression or regression of retinopathy was defined as a two-step change on the Early Treatment Diabetic Retinopathy Study final severity scale. Seventy-four subjects completed at least 3 years of follow-up, and 22% showed visual field worsening, defined as repeated significant deterioration at ‡10% of the test points, whereas only 1% showed field improvement. Worsening occurred in subjects both with and without vascular lesions. The degree of retinopathy was stable throughout the observation period in 68 of 74 eyes, improved in 4, and worsened in 2. Visual field deterioration was not correlated with a change in retinopathy. By using perimetry with an analysis tailored for monitoring diabetic subjects, we were able to demonstrate progression of retinal dysfunction over time, which may represent early signs of retinal neurodegeneration.

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Progression of Early Retinal Dysfunction in Diabetes Over Time: Results of a Long-term Prospective Clinical Study

2014

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“…The effect of neuronal apoptosis, which occurs early and is chronic in diabetes, is just now being fully appreciated. We and others (2)(3)(4)(5)(6) have reported that the neurons of the retina undergo apoptosis in both human and experimental diabetes models. However, the direct and indirect causes of neuronal dysfunction remain poorly defined.…”

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Diabetes Alters Sphingolipid Metabolism in the Retina

et al. 2006

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Dysregulated sphingolipid metabolism causes neuronal cell death and is associated with insulin resistance and diseases. Thus, we hypothesized that diabetes-induced changes in retinal sphingolipid metabolism may contribute to neuronal pathologies in diabetic retinopathy. ESI-MS/MS was used to measure ceramide content and ceramide metabolites in whole retinas after 2, 4, and 8 weeks of streptozotocin-induced diabetes. After 4 and 8 weeks of diabetes, a ϳ30% decrease in total ceramide content was observed, concomitant with a significant ϳ30% increase in glucosylceramide levels in fed diabetic rats compared with their age-matched controls. Acute insulin therapy as well as a short-term lowering of glucose via fasting did not affect the increase in glucosylceramide composition. To assess the putative biological consequences of the increase in glucosylceramide composition, R28 retinal neurons were treated with glucosylceramide synthase inhibitors. Inhibiting glycosphingolipid metabolism increased insulin sensitivity in retinal neurons. Glycosphingolipid inhibitors augmented insulin-stimulated p70 S6kinase activity in the presence of inhibitory concentrations of high glucose or glucosamine. Inhibition of glycosphingolipid synthesis also suppressed glucosamine-and interleukin-1␤-induced death. Consistent with these inhibitor studies, pharmacological accumulation of glycosphingolipids increased activation of the endoplasmic reticulum stress response, a putative modulator of insulin resistance and neuronal apoptosis. It is speculated that an increase in glucosylceramide, and possibly higher-order glycosphingolipids, could contribute to the pathogenesis of diabetic retinopathy by contributing to local insulin resistance, resulting in neuronal cell death. Thus, dysfunctional glycosphingolipid metabolism may contribute to metabolic stress in diabetes, and therapeutic strategies to restore normal sphingolipid metabolism may be a viable approach for treatment of diabetic retinopathy. Diabetes 55: [3573][3574][3575][3576][3577][3578][3579][3580] 2006

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“…DR is still usually diagnosed by visual identification of a variety of vascular lesions such as microaneurysms and lipid deposits during the fundus exam, and include the functional breakdown of the blood retinal barrier leading to macular edema [6]. But early pathology studies also identified features of cell death and degeneration in retinal tissue from humans with diabetes [7,8]. Since degenerative features in neural tissue could not be visually detected during the fundus exam they did not contribute to characterization or diagnosis of the disease.…”

Section: Diabetes Induces Apoptosis and Cell Loss In The Retinamentioning

confidence: 99%

Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

Barber

2015

Sci. China Life Sci.

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Diabetic retinopathy (DR) is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of cells in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR. retina, diabetes, neurodegeneration, visual function, vascular function, apoptosis, synapse, dendrite Citation:Barber AJ. Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss.

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Experimental Diabetic Glomerulosclerosis

Cited by 53 publications

References 0 publications

Progression of Early Retinal Dysfunction in Diabetes Over Time: Results of a Long-term Prospective Clinical Study

Progression of Early Retinal Dysfunction in Diabetes Over Time: Results of a Long-term Prospective Clinical Study

Diabetes Alters Sphingolipid Metabolism in the Retina

Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

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