Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes

Katakami, Naoto; Kaneto, Hideaki; Takahara, Mitsuyoshi; Matsuoka, Taka‐aki; Imamura, K.; Ishibashi, Fukashi; Kanda, Tsutomu; Kawai, Koichi; Osonoi, Takeshi; Matsuhisa, Munehide; Kashiwagi, Atsunori; Kawamori, Ryuzo; Shimomura, Iichiro; Yamasaki, Yuichiro

doi:10.1016/j.diabres.2011.02.017

Cited by 32 publications

(17 citation statements)

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“…In this study, the significant changes in both AKR and SDH levels in either insulin or oral‐treated groups may lead to onset as well as worsening of complications, such as retinopathy. Similarly hyperglycaemia is a strong risk factor for diabetic retinopathy . Further studies can be undertaken on a large diabetic population to show the variations in both AKR and SDH levels and their implications in the development of complications.…”

Section: Discussionmentioning

confidence: 99%

“…Variations within the AKR1B1 gene are highly significantly associated with the development of diabetic retinopathy . The AR gene has a susceptibility allele for diabetic retinopathy in type 2 diabetic patients . Progression of diabetic retinopathy is significantly inhibited by epalrestat, an AR inhibitor …”

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confidence: 99%

“…11 The AR gene has a susceptibility allele for diabetic retinopathy in type 2 diabetic patients. 12 Progression of diabetic retinopathy is significantly inhibited by epalrestat, an AR inhibitor. 13 Changes in sorbitol dehydrogenase (SDH) and AR gene expression cannot be fully explained on the basis of the osmoregulatory hypothesis, suggesting that regulation is mediated via mechanisms that are multifactorial and tissue-specific.…”

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confidence: 99%

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Aldo‐keto reductase and sorbitol dehydrogenase enzymes in Egyptian diabetic patients with and without proliferative diabetic retinopathy

Aldebasi

El-Gendy

Kamel

et al. 2013

Clinical and Experimental Optometry

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Background: Activation of the polyol pathway due to increased aldo-keto reductase (AKR) activity has been implicated in the development of diabetic complications, including proliferative diabetic retinopathy (PDR); however, the relationship between hyperglycaemia-induced activation of the polyol pathway in the retina and PDR is still uncertain. Methods: This study was conducted on 73 individuals, who were categorised into three groups: healthy individuals as normal control (15 age-matched subjects), diabetic patients treated with oral hypoglycaemic drugs (OHD, 34 patients), six of whom (17.7 per cent) were diagnosed with PDR and the rest were diagnosed with non-proliferative diabetic retinopathy (NPDR) and diabetic patients treated with insulin (INS, 24 patients), 12 of whom (50 per cent) were diagnosed with PDR and the rest had NPDR. Results: The AKR level in diabetic subjects showed a significant increase compared with the normal controls. Interestingly, AKR levels were significantly increased in the INS compared with the OHD group. Also the AKR level was significantly increased in the patients with proliferative compared with the non-proliferative retinopathy in both the insulin and oral diabetic groups. The sorbitol dehydrogenase (SDH) level in diabetic patients showed a significant decrease compared with the normal control level. Interestingly, the SDH level was significantly decreased in the INS compared with the OHD group. Also, the SDH level was significantly decreased in patients with proliferative compared with non-proliferative retinopathy in both INS and OHD groups. The HbA 1c level in both INS and OHD subjects showed a significant increase compared with normal controls. In addition, the triglyceride level in insulin proliferative retinopathy showed a significant increase compared with other groups. Conclusions: The AKR level was significantly increased in patients with proliferative compared with non-proliferative retinopathy in both insulin and oral diabetic groups. The SDH level was significantly decreased in patients with proliferative compared with nonproliferative retinopathy in both insulin and oral diabetic groups. Both AKR and SDH could be used as indicators for diabetic control.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Aldo‐keto reductase and sorbitol dehydrogenase enzymes in Egyptian diabetic patients with and without proliferative diabetic retinopathy

Aldebasi

El-Gendy

Kamel

et al. 2013

Clinical and Experimental Optometry

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“…Increased polyol pathway activity is observed in the retina from animal models of DR and from diabetic human donors with retinopathy 25 26. The link between polyol pathway and DR is further strengthened by the association between the C allele polymorphism at 106-position (the promoter of aldose reductase gene AKR1B1) and DR 27. In addition, recent evidence demonstrated that diabetes increases arginase activity in the retina, which by decreasing arginine supply for nitric oxide synthase, reduces nitric oxide levels and increase superoxide free radical generation 28.…”

Section: Oxidative Damage In Drmentioning

confidence: 99%

Putative protective role of lutein and zeaxanthin in diabetic retinopathy

et al. 2017

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Diabetic retinopathy (DR) is one of the most important microvascular complications of diabetes and remains the leading cause of blindness in the working-age individuals. The exact aetiopathogenesis of DR remains elusive despite major advances in basic science and clinical research. Oxidative damage as one of the underlying causes for DR is increasingly being recognised. In humans, three hydroxycarotenoids, lutein (L), zeaxanthin (Z) and -zeaxanthin (MZ), accumulate at the central retina (to the exclusion of all other dietary carotenoids), where they are collectively known as macular pigment. These hydroxycarotenoids by nature of their biochemical structure and function help neutralise reactive oxygen species, and thereby, prevent oxidative damage to the retina (biological antioxidants). Apart from their key antioxidant function, evidence is emerging that these carotenoids may also exhibit neuroprotective and anti-inflammatory function in the retina. Since the preliminary identification of hydroxycarotenoid in the human macula by Wald in the 1940s, there has been astounding progress in our knowledge of the role of these carotenoids in promoting ocular health. While the Age-Related Eye Disease Study 2 has established a clinical benefit for L and Z supplements in patients with age-related macular degeneration, the role of these carotenoids in other retinal diseases potentially linked to oxidative damage remains unclear. In this article, we comprehensively review the literature germane to the putative protective role of two hydroxycarotenoids, L and Z, in the pathogenesis of DR.

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“…As a result, the intracellular levels of NADPH and NAD nucleotides are preserved and normal intracellular levels of fructose and sorbitol (both of which contribute to intracellular osmolarity) maintained. This new experimental evidence, combined with the prevention of retinal changes in the AR knockout mouse (Cheung et al, 2005) and clinical findings in both type 1 and 2 patients that DR is linked to the presence of select AR alleles (Abhary et al, 2009; Demaine et al, 2000; dos Santos et al, 2006; Katakami et al, 2011; Kumaramanickavel et al, 2003; Olmos et al, 2000; Petrovic et al, 2005; Richeti et al, 2007; Szaflik et al, 2008; Uthra et al, 2010; Wang et al, 2003) merit further studies in this area.…”

Section: Introductionmentioning

confidence: 96%

Novel transgenic mouse models develop retinal changes associated with early diabetic retinopathy similar to those observed in rats with diabetes mellitus

Guo

Zhang

et al. 2014

Experimental Eye Research

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Retinal capillary pericyte degeneration has been linked to aldose reductase (AR) activity in diabetic retinopathy (DR). Since the development of DR in mice and rats has been reported to differ and that this may be linked to differences in retinal sorbitol levels, we have established new murine models of early onset diabetes mellitus as tools for investigating the role of AR in DR. Transgenic diabetic mouse models were developed by crossbreeding diabetic C57BL/6-Ins2Akita/J (AK) with transgenic C57BL mice expressing green fluorescent protein (GFP), human aldose reductase (hAR) or both in vascular tissues containing smooth muscle actin-α (SMAA). Changes in retinal sorbitol levels were determined by HPLC while changes of growth factors and signaling were investigated by Western Blots. Retinal vascular changes were quantitatively analyzed on elastase-digestion flat mounts. Results show that sorbitol levels were higher in neural retinas of diabetic AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors VEGF, IGF-1, bFGF and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK, and P-44/42 MAPK. Increased loss of nuclei per capillary length and a significant increase in the percentage of acellular capillaries presented in 18 week old AK-SMAA-GFP-hAR mice. These changes are similar to those observed in streptozotocin-induced diabetic rats. Retinal changes in both mice and rats were prevented by inhibition of AR. These studies confirm that the increased expression of AR in mice results in the development of retinal changes associated with the early stages of DR that are similar to those observed in rats.

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Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes

Cited by 32 publications

References 10 publications

Aldo‐keto reductase and sorbitol dehydrogenase enzymes in Egyptian diabetic patients with and without proliferative diabetic retinopathy

Aldo‐keto reductase and sorbitol dehydrogenase enzymes in Egyptian diabetic patients with and without proliferative diabetic retinopathy

Putative protective role of lutein and zeaxanthin in diabetic retinopathy

Novel transgenic mouse models develop retinal changes associated with early diabetic retinopathy similar to those observed in rats with diabetes mellitus

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