Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation

Liou, Gregory I.

doi:10.4239/wjd.v1.i1.12

Cited by 29 publications

(22 citation statements)

References 76 publications

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“…[8][9][10] Within the eye, disease states including glaucoma, diabetic retinopathy, and age-related macular degeneration share neuroinflammation as a common pathologic component. [11][12][13] In addition, many studies indicate that strategies for decreasing chronic inflammation prove therapeutic. 14,15 Therefore, microglia-mediated responses to inflammatory stimuli are treatment targets for vision-threatening diseases.…”

mentioning

confidence: 98%

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Zhao

Liou

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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confidence: 98%

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Zhao

Liou

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…Of additional interest, recent studies of DR in experimental models suggest the P2X7 receptors may have a role in mediating cytokine-induced vascular inflammatory reactions that can degrade the integrity of the bloodretinal barrier and thereby contribute to retinal vascular occlusion and ischemia [34] . More specifically, there are a number of reports linking P2X7 receptor activation in the retina with the expression of inflammatory cytokines [35] .…”

Section: Retinopathymentioning

confidence: 99%

Role of P2X₇ receptors in the development of diabetic retinopathy

Sugiyama¹

2014

WJD

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The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation. Key words: P2X7 receptor; Diabetic retinopathy; Vasotoxicity; Retinal microvessels; Interleukin-1β; Tumor necrosis factor-α Core tip: This review summarizes the studies regarding the putative role of the P2X7 receptor in triggering purinergic vasotoxicity in the retina and thereby contributing to the progression of diabetic retinopathy.Sugiyama T. Role of P2X7 receptors in the development of diabetic retinopathy.

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“…1 2 DR is characterised by retinal vessels basement membrane thickening, loss of pericytes and endothelial cells, blood-retinal barrier breakdown, capillary non-perfusion, microaneurysms, haemorrhages and neovascularisation. 3 Several molecules and biochemical pathways like polyol pathway, activation of protein kinase C, formation of advanced glycation end products (AGEs), oxidative stress, upregulation of growth factors, adhesion molecules, etc have been implicated in the pathogenesis of DR. Recent research insights describe DR as a retinal disease associated with vascular neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

ICAM-1K469E polymorphism is a genetic determinant for the clinical risk factors of T2D subjects with retinopathy in Indians: a population-based case–control study

Vinita

Sripriya²,

Prathiba

et al. 2012

BMJ Open

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ObjectiveElevated levels of intercellular adhesion molecule-1 (ICAM-1) are demonstrated in diabetes complications. The current study aims to understand association of K469E (rs5498) in ICAM-1 gene, in type 2 diabetic (T2D) subjects with retinopathy.DesignCase–control study.SettingSankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study, an epidemiology study (on prevalence of diabetic retinopathy in T2D subjects (T2DR) from south India) and outpatient department of Sankara Nethralaya, a tertiary care hospital, in Chennai, India.ParticipantsA total of 356 T2D subjects of >15 years of diabetes duration, with (n=199) and without (n=157) retinopathy.MethodsThe rs5498 polymorphism was genotyped by direct sequencing. Multivariate analysis for various clinical covariates was done using SPSS V.14. Comparative assessment of structure stability, folding rate of the variants were assessed using bioinformatics tools like STRIDE, MuPro, ModellerV97, fold rate server, etc.ResultsThe AA genotype of rs5498 was seen at a higher frequency in the retinopathy group (p=0.012). The risk for diabetic retinopathy (DR) increased in the presence of AA genotype (OR=1.89–4.82) after the sequential addition of various clinical covariates. Multivariate logistic regression analysis showed 8.26 times high risk for developing DR in the AG genotype (p=0.003). Structural superimposition of ICAM-1 wild type (K469) and variant (E469) showed 0.943 Å of backbone root mean square deviation as calculated by PYMOL software. A difference in the fold rate time was also observed between the wild type (5.4/s) and variant (3.3/s).ConclusionsThis study shows that allele A of rs5498 in ICAM-1 is a putative risk predisposing allele for T2D retinopathy and its clinical covariates in Indian population. The folding rate of the protein decreases for the A allele implicating a potential effect on the structure and function of ICAM-1.

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Diabetic retinopathy: Role of inflammation and potential therapies for anti-inflammation

Cited by 29 publications

References 76 publications

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Role of P2X₇ receptors in the development of diabetic retinopathy

ICAM-1K469E polymorphism is a genetic determinant for the clinical risk factors of T2D subjects with retinopathy in Indians: a population-based case–control study

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