Elevated vitreous nitric oxide levels in patients with proliferative diabetic retinopathy

Yılmaz, Gürsel; Esser, Peter; Kociek, Norbert; Aydin, Pınar; Heimann, Klaus

doi:10.1016/s0002-9394(00)00398-6

Cited by 44 publications

(38 citation statements)

References 26 publications

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“…Recently Yilmaz et al found elevated NO levels in the vitreous of diabetic patients with proliferative diabetic retinopathy compared to controls. 44 We haven't found significant differences in NO levels between smokers and non-smokers although smoking is a well known oxidative factor.…”

Section: Discussionmentioning

confidence: 72%

Protective role of oral antioxidant supplementation in ocular surface of diabetic patients

Peponis

Papathanasiou²,

Kapranou³

et al. 2002

British Journal of Ophthalmology

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Aim: To investigate the effect of vitamin C and E supplementation in the levels of nitrite, nitric oxide (NO) related metabolite, and ocular surface parameters in diabetic patients. Methods: 50 patients with non-insulin dependent diabetes mellitus were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) supplementation for 10 days. Nitrite levels in tears were measured by photometric determination before and after vitamin supplementation. Tear function parameters (Schirmer test I, BUT, ocular ferning test) and brush cytology analysis of the conjunctival epithelium were also evaluated. Results: Nitrite levels were found to be significantly reduced (p<0.05) after 10 days of vitamin C and E supplementation. Improved values for Schirmer test, BUT test, and ocular ferning test were also found. Goblet cell density and grading of squamous metaplasia showed a significant improvement. Conclusions: Oxidative stress and free radical production are elevated in diabetes mellitus. Antioxidants, such as vitamin C and vitamin E, probably have an important role in reducing the oxidative damage produced by nitric oxide and other free radicals and improving the ocular surface milieu.

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Section: Discussionmentioning

confidence: 72%

Protective role of oral antioxidant supplementation in ocular surface of diabetic patients

Peponis

Papathanasiou²,

Kapranou³

et al. 2002

British Journal of Ophthalmology

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“…12 Previous reports have shown increased levels of nitrate and nitrite (NO) in PDR. [12][13][14] Our results suggest that diabetic patients show no significant differences from controls in their vitreal NO concentrations, even though the diabetic patients did have lower levels compared to controls. These differences in results may be related to the method of analysing NO levels and the nature of NO itself.…”

Section: Discussionmentioning

confidence: 89%

Concentration of haemodynamic and inflammatory related cytokines in diabetic retinopathy

Patel

Saleh²,

Hykin

et al. 2006

Eye

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Aim There are changes in blood flow during the clinical stages of diabetic retinopathy with increasing leukostasis and secondary elaboration of cytokines. This study evaluated the vitreous concentrations of haemodynamicrelated (endothelin-1 (ET-1) and nitric oxide (NO)), inflammatory and anti-inflammatory (interleukin-1 receptor antagonist, IL-1 Ra) cytokines in the diabetic patients (with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)), compared them with those of control patients (full thickness macular hole, FTMH) and correlated to macular structural indices. Method Vitreous samples from five FTMH patients representing normal controls were analysed together with the vitreous samples of 15 patients with NPDR and five with PDR. The vitreous concentrations of nitrite (total NO), ET-1, and prostacyclin was determined using ELISA kits (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions. A sandwich luminescent immunoassay technique was used to determine IL-1b and IL-1 Ra concentrations. Results In the different clinical groups, there were no differences in the vitreous NO and prostacyclin concentrations. In NPDR, the median ET-1 concentration (0.7 pg/ml SD 70.8 pg/ml) was significantly reduced (Po0.05), compared to PDR (6.35 pg/ml SD 70.6 pg/ml) and FTMH (3.6 pg/ml SD 70.14 pg/ml). Its concentration also positively correlated with foveal thickness and macular volume (Po0.05) in patients with NPDR and macular oedema. IL-1 b was detected in PDR, and diabetic patients demonstrated a lower concentration of the anti-inflammatory cytokine IL-1 Ra.Conclusion Reduced concentrations of ET-1 in NPDR may reflect the haemodynamic changes of NPDR. The IL-1 Ra concentration suggests a change in the anti-inflammatory environment of the diabetic retina.

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“…Yilmaz and coworkers [26] reported a fivefold elevation of NO in the vitreous of patients with proliferative diabetic retinopathy compared with nondiabetic control patients. Given that NO levels are increased in diabetic retinopathy [23][24][25][26], coupled with our findings that NO can upregulate system x c -transporter in RPE cells [4], we asked whether this transporter is present in ganglion cells and if so, whether it is upregulated by NO in these cells.…”

Section: Introductionmentioning

confidence: 98%

Expression of the cystine-glutamate exchanger (xc −) in retinal ganglion cells and regulation by nitric oxide and oxidative stress

et al. 2006

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Purpose-The cystine-glutamate transporter, system x c -, mediates the Na + -independent exchange of cystine into cells coupled to the efflux of intracellular glutamate. Within cells, cystine is reduced to cysteine, a component of glutathione, thus system x c -plays a critical role in glutathione homeostasis. Studies in brain had initially suggested that system x c -was present primarily in astrocytes and not neurons, but more recent work suggests that certain brain neurons have an active system x c -. In the retina, system x c -has been demonstrated in retinal Müller and RPE cells. Recent immunohistochemical work from our lab suggested that the two protein components of system x c -, xCT and 4F2hc, are present in ganglion cells of the intact retina. The purpose of this investigation was to determine whether system x c -was present in primary ganglion cells isolated from neonatal mouse retinas and, if so, to study its regulation by oxidative stress in a retinal ganglion cell line, RGC-5.Methods-The presence of xCT and 4F2hc in RGC-5 cells was established by RT-PCR, immunoblotting and immunohistochemistry and in primary mouse retinal ganglion cells by immunoblotting and immunohistochemistry; the function of the transporter in RGC-5 cells was established by measuring radiolabeled glutamate uptake in the absence of Na + . To assess regulation of system x c -by oxidative stress in ganglion cells, RGC-5 cells were incubated in the presence or absence of nitric oxide (NO) donors (3-nitroso-N-acetylpenicillamine (SNAP), Snitrosoglutathione (SNOG), or 3-morpholinosydnonimine hydrochloride (SIN-1) and reactive oxygen species (ROS) donors menadione sodium bisulfite, hydrogen peroxide and xanthine sodium salt/xanthine oxidase and system x c -was analyzed using functional assays, RT-PCR and immunoblotting.Results-RGC-5 cells and primary ganglion cells isolated from mouse retina express xCT and 4F2hc as demonstrated by RT-PCR, immunoblotting and immunohistochemistry. RGC-5 cells take up glutamate in the absence of Na + and this uptake was blocked by known inhibitors of system x c -, glutamate, cysteine, and cystine as well as quisqualic acid. Treatment of RGC-5 cells with NO donors and donors of ROS led to an increase in the functional activity of system x c -. Kinetic analysis of SNAP-treated RGC-5 cells compared to control cells showed that the increase was associated with an increase in the maximal velocity of the transporter with no significant change in the substrate affinity. Molecular analyses showed that the upregulation is associated with an increase in the expression of xCT with no detectable change in the expression of 4F2hc. Conclusions-RGC-5 cells and ganglion cells isolated from neonatal mice express the cystine/ glutamate transporter x c -(the light chain xCT and the heavy chain 4F2hc) as is evident from functional and molecular studies. Oxidative stress upregulates this transport system in RGC-5 cells and the process is associated with an increase in xCT mRNA and protein but no change in 4F2hc mRNA or...

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Elevated vitreous nitric oxide levels in patients with proliferative diabetic retinopathy

Cited by 44 publications

References 26 publications

Protective role of oral antioxidant supplementation in ocular surface of diabetic patients

Protective role of oral antioxidant supplementation in ocular surface of diabetic patients

Concentration of haemodynamic and inflammatory related cytokines in diabetic retinopathy

Expression of the cystine-glutamate exchanger (xc −) in retinal ganglion cells and regulation by nitric oxide and oxidative stress

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