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

Manju L Subramanian,Steven Ness,Sayon Roy,Marissa G Fiorello,Thor D Stein,Nicole Siegel,Dongjoon Kim

doi:10.3390/cells8101122

Manju L Subramanian, Steven Ness + Show 5 more

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https://doi.org/10.3390/cells8101122

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Abstract

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.

Highlights

Diabetic retinopathy (DR) is the leading cause of vision impairment and blindness among working-age adults [1]
Is compromised by high glucose (HG)-induced lysyl oxidase (LOX) upregulation and increased activity, which leads to breakdown of blood-retinal-barrier (BRB) characteristics associated with diabetic retinopathy [9]
We examined whether LOX levels were altered in vitreous samples freshly isolated from diabetic subjects with advanced proliferative DR (PDR) and non-diabetic subjects

Summary

Introduction

Diabetic retinopathy (DR) is the leading cause of vision impairment and blindness among working-age adults [1]. The early stages of diabetic retinopathy are marked by the development of thickened capillary basement membrane (BM), formation of acellular capillaries and pericyte ghosts, and the clinical manifestation of vascular hyperpermeability in the retina [2,3,4]. A critical function of the BM is its ability to act as a selective permeable barrier, and diabetes-induced alteration of its ultrastructure is known to promote vascular permeability [5]. While excess synthesis of BM components contributes to BM thickening, lysyl oxidase (LOX), a key enzyme responsible for the maturation and development of BM, has been implicated in regulating the ultrastructural integrity of the BM [8]. The functionality of the thickened BM is compromised by high glucose (HG)-induced LOX upregulation and increased activity, which leads to breakdown of blood-retinal-barrier (BRB) characteristics associated with diabetic retinopathy [9]

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