Upregulation of Lysyl Oxidase Expression in Vitreous of Diabetic Subjects: Implications for Diabetic Retinopathy

Animal studies have shown diabetes-induced lysyl oxidase (LOX) upregulation promotes blood-retinal-barrier breakdown and retinal vascular cell loss associated with diabetic retinopathy (DR). However, it is unclear whether changes in LOX expression contribute to the development and progression of DR. To determine if vitreous LOX levels are altered in patients with DR, 31 vitreous specimens from subjects with advanced proliferative DR (PDR), and 27 from non-diabetics were examined. The two groups were age- and gender-matched (57 ± 12 yrs vs. 53 ± 18 yrs; 19 males and 12 females vs. 17 males and 10 females). Vitreous samples obtained during vitrectomy were assessed for LOX levels using ELISA. LOX was detected in a larger number of PDR subjects (58%) than in non-diabetic subjects (15%). Additionally, ELISA measurements showed a significant increase in LOX levels in the diabetic subjects with PDR, compared to those of non-diabetic subjects (68.3 ± 112 ng/mL vs. 2.1 ± 8.2 ng/mL; p < 0.01). No gender difference in vitreous LOX levels was observed in either the diabetic or non-diabetic groups. Findings support previous reports of increased LOX levels in retinas of diabetic animals and in retinal vascular cells in high glucose condition, raising the prospect of targeting LOX overexpression as a potential target for PDR treatment.

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Multiple Gene Polymorphisms Associated with Exfoliation Syndrome in the Uygur Population

Journal of Ophthalmology ◽

10.1155/2019/9687823 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yi-Nu Ma ◽

Ting-Yu Xie ◽

Xue-Yi Chen

Keyword(s):

Protective Factor ◽

Lysyl Oxidase ◽

Direct Sequencing ◽

Control Group ◽

Exfoliation Syndrome ◽

Nucleotide Polymorphisms ◽

Age And Gender ◽

Protective Allele ◽

Significant Difference ◽

And Gender

Background. Our previous data suggested that three single-nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, of the lysyl oxidase-like 1 gene (LOXL1) are significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). The following study investigated other SNPs that potentially effect XFS/XFG. Methods. A total of 216 Uygur patients diagnosed with XFS/XFG, and 297 Uygur volunteers were admitted to the First Affiliated Hospital at Xinjiang Medical University between January 2015 and October 2017. Blood samples were collected by venipuncture. Alleles and genotypes of LOXL1, TBC1D21, ATXN2, APOE, CLU, AFAP1, TXNRD2, CACNA1A, ABCA1, GAS7, and CNTNAP2 were analyzed by direct sequencing. Results. The allele G of rs41435250 of LOXL1 was a risk allele for XFS/XFG (P<0.001), whereas the allele G of rs893818 of LOXL1 was a protective allele for XFS/XFG (P<0.001). After adjusting all data for age and gender, the following results were obtained: the frequency of genotype CC for rs7137828 of ATXN2 was significantly higher in XFS/XFG patients than in controls (P=0.027), while no significance was found with reference to the frequency of genotype TT. The frequency of genotype GG for rs893818 of LOXL1 (P<0.001) and the frequency of genotype AA were both significantly higher in XFS/XFG groups compared to the control group (P<0.001). In addition, the frequency of genotype TT for rs41435250 of LOXL1 was higher in XFS/XFG patients than in controls (P=0.003), while no significant difference was found with reference to the frequency of genotype GG after adjusting for age and gender. In addition, the haplotypes G-A/T-G/G-G for rs41435250 and rs893818 were significantly associated with XFS/G. Conclusions. With reference to LOXL1, the rs41435250 resulted as a risk factor and rs893818 as a protective factor for XFS/XFG in the Uygur populations. Meanwhile, the rs16958445 of TBC1D21 and the rs7137828 of ATXN2 have also shown to be associated with pathogenesis of XFS/XFG.

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Asymmetric dimethylarginine aggravates blood–retinal barrier breakdown of diabetic retinopathy via inhibition of intercellular communication in retinal pericytes

Amino Acids ◽

10.1007/s00726-019-02788-1 ◽

2019 ◽

Vol 51 (10-12) ◽

pp. 1515-1526 ◽

Cited By ~ 1

Author(s):

Chu-Yi Huang ◽

Ting Zhou ◽

Ge Li ◽

Ming-Yuan Li ◽

Xiao-Ming Xiong ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Intercellular Communication ◽

Asymmetric Dimethylarginine ◽

Blood Retinal Barrier ◽

Retinal Pericytes ◽

Barrier Breakdown

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Inhibition of Protein Kinase C δ Attenuates Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

American Journal Of Pathology ◽

10.2353/ajpath.2010.090398 ◽

2010 ◽

Vol 176 (3) ◽

pp. 1517-1524 ◽

Cited By ~ 45

Author(s):

Jeong-Hun Kim ◽

Jin Hyoung Kim ◽

Hyoung-Oh Jun ◽

Young Suk Yu ◽

Kyu-Won Kim

Keyword(s):

Diabetic Retinopathy ◽

Protein Kinase C ◽

Protein Kinase ◽

Blood Retinal Barrier ◽

Kinase C ◽

Barrier Breakdown

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Cross-Talk between Sirtuin 1 and the Proinflammatory Mediator High-Mobility Group Box-1 in the Regulation of Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

Current Eye Research ◽

10.1080/02713683.2019.1625406 ◽

2019 ◽

Vol 44 (10) ◽

pp. 1133-1143 ◽

Cited By ~ 4

Author(s):

Ghulam Mohammad ◽

Ghada Maher Abdelaziz ◽

Mohammad Mairaj Siddiquei ◽

Ajmal Ahmad ◽

Gert De Hertogh ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Cross Talk ◽

High Mobility ◽

Sirtuin 1 ◽

High Mobility Group ◽

Blood Retinal Barrier ◽

Proinflammatory Mediator ◽

Barrier Breakdown

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Role of Peoxisome Proliferator Activator Receptor on Blood Retinal Barrier Breakdown

PPAR Research ◽

10.1155/2008/679237 ◽

2008 ◽

Vol 2008 ◽

pp. 1-4 ◽

Cited By ~ 6

Author(s):

Yasuo Yanagi

Keyword(s):

Diabetic Retinopathy ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Critical Role ◽

Blood Retinal Barrier ◽

Early Diabetes ◽

Pathological Conditions ◽

Barrier Breakdown ◽

Brb Breakdown

The retinal vessels have two barriers: the retinal pigment epithelium and the retinal vascular endothelium. Each barrier exhibits increased permeability under various pathological conditions. This condition is referred to as blood retinal barrier (BRB) breakdown. Clinically, the most frequently encountered condition causing BRB breakdown is diabetic retinopathy. In recent studies, inflammation has been linked to BRB breakdown and vascular leakage in diabetic retinopathy. Biological support for the role of inflammation in early diabetes is the adhesion of leukocytes to the retinal vasculature (leukostasis) observed in diabetic retinopathy. is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in a variety of biological processes, including adipogenesis, glucose metabolism, angiogenesis, and inflammation. There is now strong experimental evidence to support the theory that inhibits diabetes-induced retinal leukostasis and leakage, playing an important role in the pathogenesis of diabetic retinopathy. Therapeutic targeting of may be beneficial to diabetic retinopathy.

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