Susceptibility of Streptozotocin-Induced Diabetic Rat Retinal Function and Ocular Blood Flow to Acute Intraocular Pressure Challenge

Wong, Vickie; Vingrys, Algis J.; Jobling, Andrew I

doi:10.1167/iovs.13-11595

Cited by 11 publications

(18 citation statements)

References 59 publications

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“…These functional abnormalities are mainly neuronal in origin; and neuronal cell apoptosis can be seen as early as one month after induction of diabetes [34,35]. Abnormal ERG responses appear before vascular lesions begin to appear; streptozotocin-induced diabetic rats present delayed ERG responses within one month of induction of diabetes [36], while retinal capillary cell apoptosis and histopathology are not observed till the duration is extended to at least 6 months [32]. Similarly, alterations in multifocal ERG are considered to predict the onset and progression of retinopathy in diabetic patients [37,38].…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

et al. 2014

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PurposeIncreased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for ‘Diabetes Vision Function’, on diabetic retinopathy.MethodsStreptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at ~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1β and NF-kB.ResultsDiabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3–4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1β and NF-kB levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities.ConclusionsNutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow progressing disease feared most by diabetic patients.

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Section: Discussionmentioning

confidence: 99%

Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

et al. 2014

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“…Hyperglycemia has multiple effects that can potentially impact not only AION onset [11][12][13] and second eye involvement, 14,15 but also visual outcome once optic nerve ischemia occurs. Other than the well-known effects of hyperglycemia on blood vessels, [31][32][33][34][35] there is also evidence that diabetes increases cellular inflammation, [36][37][38][39] which can be directly attributed to hyperglycemia. 40 In hyperglycemia, there is known upregulation of levels of retinal VEGF, which is secreted by Müller cells in vivo and in vitro, [41][42][43] which can prime the hyperglycemic retinal milieu to develop greater swelling and more prominent inflammation in ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…Three weeks after diabetes induction, which is considered sufficient time to induce chronic diabetes, 31 we induced experimental AION using photochemical thrombosis 23,25,26 following injection of rose bengal (1.25 mM in phosphatebuffered saline, 5 lL/g body weight) in tail vein using transpupillary laser light with a frequency doubled Nd:YAG laser (Pascal; OptiMedica, Santa Clara, CA, USA) at 400-lm spot diameter (50 mW power, 1 second duration, 15 spots). To ensure consistency of studies, the same person performed AION induction in all experiments, and one eye in each mouse had AION induction, whereas the contralateral (fellow) eye served as control.…”

Section: Experimental Aion and Experimental Groupsmentioning

confidence: 99%

Experimental Anterior Ischemic Optic Neuropathy in Diabetic Mice Exhibited Severe Retinal Swelling Associated With VEGF Elevation

Sun

Shariati

Liao

2017

Invest. Ophthalmol. Vis. Sci.

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In the setting of hyperglycemia, AION led to greater acute, postischemic microglial activation and elevation of VEGF levels, which likely contributed to greater retinal swelling acutely and worse retinal thinning and loss of retinal ganglion cells chronically. Treatment of hyperglycemia with insulin reduced VEGF levels and retinal swelling, consistent with the idea that VEGF is an important factor in postischemic swelling and that good glycemic control following AION may lead to better visual outcome.

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“…Ocular blood flow was measured using laser Doppler flowmetry in a manner similar to previous studies (Kiel and van Heuven ; Wong et al. ). To determine the origin of the LDF signal, a pilot study (He et al.…”

Section: Methodsmentioning

confidence: 99%

“…Ocular blood flow was measured using laser Doppler flowmetry in a manner similar to previous studies (Kiel and van Heuven 1995;Wong et al 2013). To determine the origin of the LDF signal, a pilot study (He et al 2012, online supplement) showed that hyperoxemia induced by pure oxygen breathing suppressed the LDF signal by 18%.…”

Section: Experimental Protocolmentioning

confidence: 99%

Coupling blood flow and neural function in the retina: a model for homeostatic responses to ocular perfusion pressure challenge

Lim

Nguyen

et al. 2013

Physiol Rep

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Retinal function is known to be more resistant than blood flow to acute reduction of ocular perfusion pressure (OPP). To understand the mechanisms underlying the disconnect between blood flow and neural function, a mathematical model is developed in this study, which proposes that increased oxygen extraction ratio compensates for relative ischemia to sustain retinal function. In addition, the model incorporates a term to account for a pressure-related mechanical stress on neurons when OPP reduction is achieved by intraocular pressure (IOP) elevation. We show that this model, combining ocular blood flow, oxygen extraction ratio, and IOP mechanical stress on neurons, accounts for retinal function over a wide range of OPP manipulations. The robustness of the model is tested against experimental data where ocular blood flow, oxygen tension, and retinal function were simultaneously measured during acute OPP manipulation. The model provides a basis for understanding the retinal hemodynamic responses to short-term OPP challenge.

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Susceptibility of Streptozotocin-Induced Diabetic Rat Retinal Function and Ocular Blood Flow to Acute Intraocular Pressure Challenge

Abstract: STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNos expression and to autoregulate blood flow in response to stress.

Cited by 11 publications

References 59 publications

Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

Experimental Anterior Ischemic Optic Neuropathy in Diabetic Mice Exhibited Severe Retinal Swelling Associated With VEGF Elevation

Coupling blood flow and neural function in the retina: a model for homeostatic responses to ocular perfusion pressure challenge

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