Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

Kizawa, Junya; Machida, Shigeki; Kobayashi, Takaki; Gotoh, Yasutaka; Kurosaka, Daijiro

doi:10.1007/s10384-006-0326-0

Cited by 121 publications

(107 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our ERG analyses demonstrated the reduced amplitude and prolonged implicit time of OPs in diabetic mice, in accordance with clinical and experimental data on attenuated OP changes in early diabetes (1,2,29). Importantly, AT1R blockade significantly improved these functional parameters in the diabetic retina to the normal levels observed in nondiabetic controls (Fig.…”

Section: At1r-mediated Retinal Dysfunction In Diabetessupporting

confidence: 89%

“…2). OP changes including the reduced amplitude and prolonged implicit time are known to occur in the early stage of murine and human diabetic retinopathy (1,2,20,21). There was no remarkable difference in a-or b-wave among nondiabetes and 4-week diabetes treated with vehicle, telimsartan, and valsartan (data not shown).…”

Section: At1r-mediated Retinal Dysfunction In Diabetesmentioning

confidence: 87%

“…The earliest functional disruption clinically detectable is changes in oscillatory potentials (OPs) measured by electroretinography (ERG) (1,2). The cellular source of OPs is regarded as retinal neurons with synapse formation in the inner retina, including bipolar and amacrine cells (3).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Pathogenic mechanisms underlying diabetesinduced retinal dysfunction are not fully understood. The aim of the present study was to show the relationship of the reninangiotensin system (RAS) with the synaptic vesicle protein synaptophysin and neuronal activity in the diabetic retina.RESEARCH DESIGN AND METHODS-C57BL/6 mice with streptozotocin-induced diabetes were treated with the angiotensin II type 1 receptor (AT1R) blocker telimsartan or valsartan, and retinal function was analyzed by electroretinography. Retinal production of the RAS components and phosphorylation of ERK (extracellular-signal regulated kinase) were examined by immunoblotting. Retinal mRNA and protein levels of synaptophysin were measured by quantitative RT-PCR and immunoblot analyses, respectively. In vitro, synaptophysin levels were also evaluated using angiotensin II-stimulated PC12D neuronal cells cultured with or without the inhibition of ERK signaling or the ubiquitin-proteasome system (UPS).RESULTS-Induction of diabetes led to a significant increase in retinal production of angiotensin II and AT1R together with ERK activation in the downstream of AT1R. AT1R blockade significantly reversed diabetes-induced electroretinography changes and reduction of synaptophysin protein, but not mRNA, levels in the diabetic retina. In agreement with the AT1R-mediated posttranscriptional downregulation of synaptophysin in vivo, in vitro application of angiotensin II to PC12D neuronal cells caused the UPS-mediated degradation of synaptophysin protein via AT1R, which proved to be induced by ERK activation.CONCLUSIONS-These data indicate the first molecular evidence of the RAS-induced synaptophysin degradation and neuronal dysfunction in the diabetic retina, suggesting the possibility of the AT1R blockade as a novel neuroprotective treatment for diabetic retinopathy.

show abstract

Section: At1r-mediated Retinal Dysfunction In Diabetessupporting

confidence: 89%

Section: At1r-mediated Retinal Dysfunction In Diabetesmentioning

confidence: 87%

See 1 more Smart Citation

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Microangiopathy is a common characteristic of diabetic retinopathy; however, impaired vision begins prior to the appearance of an obvious vascular lesion in this disease [3,4]. At the early stage of this disease, impaired inner retinal function was detected by observing the oscillatory potentials (OPs) recorded by electroretinogram (ERG) [3,4].…”

Section: Neuroinflammatory Signaling and Cellular Disorders In The Rementioning

confidence: 99%

“…At the early stage of this disease, impaired inner retinal function was detected by observing the oscillatory potentials (OPs) recorded by electroretinogram (ERG) [3,4]. In parallel, atrophy or thinning of the inner retinal layer was also reported, based on optical Coherent Tomography (OCT) observations, in diabetes patients with no detectable clinical diabetic retinopathy [5].…”

Section: Neuroinflammatory Signaling and Cellular Disorders In The Rementioning

confidence: 99%

Neuroinflammation and Neurodegenerative Disorders of the Retina

Ozawa¹,

Kamoshita²,

Narimatsu³

et al. 2012

Endocrinol Metab Synd

View full text Add to dashboard Cite

The retina is composed of neural networks that are responsible for visual function, and vascular networks that support the tissue. Although vascular targeting therapies for retinal diseases have recently been developed, therapies directly targeting the neuronal component of these diseases have yet to be developed. Here, we review recent studies describing the pathological signaling that occurs within the neuronal cells of retinal disease models. The molecular changes caused by endogenous or exogenous factors in the retinal neural cells and the molecular events involved in neuroinflammation are illustrated. These underlying molecular mechanisms reveal promising targets for new therapeutic approaches for retinal neural disorders.

show abstract

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human‐like macula

Hammoum

Benlarbi²,

Dellaa³

et al. 2017

J of Comparative Neurology

View full text Add to dashboard Cite

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases.

show abstract

Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

Cited by 121 publications

References 29 publications

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

Neuroinflammation and Neurodegenerative Disorders of the Retina

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human‐like macula

Contact Info

Product

Resources

About