Effects of High Glucose–Induced Lysyl Oxidase Propeptide on Retinal Endothelial Cell Survival

Kim, Dongjoon; Lee, Dayeun; Trackman, Philip C.; Roy, Sayon

doi:10.1016/j.ajpath.2019.06.004

Cited by 14 publications

(6 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hyperglycemia can initiate many biochemical changes in the retinal microvasculature, including increased oxidative stress in the polyol pathway, protein kinase C (PKC) activation, and advanced glycation end-product formation [61] (Figure 3). Rat retinal endothelial cells exposed to high glucose (HG) showed a down-regulation of the protein kinase B (also known as AKT) pathway and increased apoptosis [62]. HG was also found to increase mitochondrial fragmentation and pro-apoptotic cytochrome c levels in vascular cells of rat retinal capillaries [63,64].…”

Section: Diabetic Retinopathymentioning

confidence: 99%

A Mechanistic Review of β-Carotene, Lutein, and Zeaxanthin in Eye Health and Disease

et al. 2020

View full text Add to dashboard Cite

Carotenoids are natural lipid-soluble antioxidants abundantly found as colorful pigments in fruits and vegetables. At least 600 carotenoids occur naturally, although about 20 of them, including β-carotene, α-carotene, lycopene, lutein, zeaxanthin, meso-zeaxanthin, and cryptoxanthin, are detectable in the human blood. They have distinct physiological and pathophysiological functions ranging from fetal development to adult homeostasis. β-carotene is a precursor of vitamin A that essentially functions in many biological processes including vision. The human macula lutea and eye lens are rich in lutein, zeaxanthin, and meso-zeaxanthin, collectively known as macular xanthophylls, which help maintain eye health and prevent ophthalmic diseases. Ocular carotenoids absorb light from the visible region (400–500 nm wavelength), enabling them to protect the retina and lens from potential photochemical damage induced by light exposure. These natural antioxidants also aid in quenching free radicals produced by complex physiological reactions and, consequently, protect the eye from oxidative stress, apoptosis, mitochondrial dysfunction, and inflammation. This review discusses the protective mechanisms of macular xanthophylls in preventing eye diseases such as cataract, age-related macular degeneration, and diabetic retinopathy. Moreover, some preclinical animal studies and some clinical trials are discussed briefly to understand carotenoid safety and efficacy.

show abstract

Section: Diabetic Retinopathymentioning

confidence: 99%

A Mechanistic Review of β-Carotene, Lutein, and Zeaxanthin in Eye Health and Disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…There was no difference in the LOX levels of vitreous samples derived from male and female subjects in both the diabetic group and the non-diabetic group. Of note, our recent study indicated that mannitol used as osmotic control showed no effects on LOX levels in retinal endothelial cells in vitro [34].…”

Section: Resultsmentioning

confidence: 99%

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

Mahadevan

Stein

Siegel

et al. 2019

Cells

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…In CDAA-induced NASH model, our rst observations indicated that LOXL1 were strongly expressed in activation HSCs and also in endothelial cells positioned between the plates of hepatocytes, suggested that abnormal expression of LOXL1 was different from the CCl 4 induced brosis model. Many reports indicate that LOX or LOXL2 predominantly expressed in HSCs, but also expressed in injured hepatocytes or endothelial cells under pathological conditions (13,(19)(20)(21), especially under metabolic disorders condition. We speculated that different etiology of the liver diseases would display differences in the expression patterns of LOXL1.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Stellate Cells-Specific Loxl1 Deficiency Abrogates Hepatic Inflammation, Fibrosis, and Corrects Lipid Metabolic Abnormalities in Non-Obese NASH Mice

Yang

Yan

et al. 2021

SSRN Journal

View full text Add to dashboard Cite

Background & Aims: Lysyl oxidase-like-1 (LOXL1), a vital crosslinking enzyme in extracellular matrix (ECM) protein maintenance, is well established in brosis via mediating ECM stabilization. However, the potential role of LOXL1 in the pathogenesis of nonalcoholic steatohepatitis (NASH) has not been previously studied. Methods: We generated Loxl1 / mice to selectively delete Loxl1 in hepatic stellate cells (HSCs) (Loxl1 / Gfap cre ; Loxl1 / as littermate controls) and then examined liver pathology and metabolic context in Loxl1 / Gfap cre fed a choline-de cient L-amino acid-de ned (CDAA) diet or an isocaloric control diet for 16 weeks. We con rmed study ndings in 23 patients with biopsy-proven NAFLD. Results: LOXL1 was signi cantly increased in CDAA induced non-obese NASH compared with control diet. Here, utilizing a HSCs-speci c deletion of Loxl1 model, we found that Loxl1 de cient in HSCs ameliorated CDAA-induced in ammation and brosis, with reduced expression of pro-in ammation and pro-brogenic genes. Interestingly, CDAA-fed Loxl1 de cient mice was associated with improved body weight and attenuated hepatic steatosis and to an up-regulation of leptin in adipose tissue and in serum, without changes in hepatic lipogenesis gene expression, compared with CDAA-fed control mice. Most importantly, analyses of serum LOXL1 and leptin levels from NAFLD patients revealed that LOXL1 was positively correlated with histological brosis progression, whereas was inversely correlated with leptin levels, especially in non-obese NAFLD patients. Conclusion: In a mouse model of CDAA-induced non-obese NASH, selective deletion of Loxl1 from HSCs attenuated steatohepatitis, hepatic brosis and improved lipid metabolic abnormalities. Hence, LOXL1 inhibition may serve as a new therapeutic strategy for NASH.

show abstract

Effects of High Glucose–Induced Lysyl Oxidase Propeptide on Retinal Endothelial Cell Survival

Cited by 14 publications

References 38 publications

A Mechanistic Review of β-Carotene, Lutein, and Zeaxanthin in Eye Health and Disease

A Mechanistic Review of β-Carotene, Lutein, and Zeaxanthin in Eye Health and Disease

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

Hepatic Stellate Cells-Specific Loxl1 Deficiency Abrogates Hepatic Inflammation, Fibrosis, and Corrects Lipid Metabolic Abnormalities in Non-Obese NASH Mice

Contact Info

Product

Resources

About