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

Cells. 2019 Sep 21;8(10):1122. doi: 10.3390/cells8101122.

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.

Keywords: diabetic retinopathy; hyperglycemia; lysyl oxidase; retinal lesions.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Case-Control Studies
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Protein-Lysine 6-Oxidase / metabolism*
  • Retrospective Studies
  • Severity of Illness Index
  • Up-Regulation
  • Vitrectomy
  • Vitreoretinopathy, Proliferative / diagnosis
  • Vitreoretinopathy, Proliferative / metabolism
  • Vitreoretinopathy, Proliferative / pathology
  • Vitreous Body / metabolism*
  • Vitreous Body / pathology

Substances

  • Biomarkers
  • LOX protein, human
  • Protein-Lysine 6-Oxidase