Unbalanced Vitreous Levels of Osteoprotegerin, RANKL, RANK, and TRAIL in Proliferative Diabetic Retinopathy

ABSTRACT

Purpose: We investigated the expression of the proinflammatory and proangiogenic factor osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and the receptor RANK in proliferative diabetic retinopathy (PDR).

Materials and methods: Vitreous samples from PDR and nondiabetic control patients and epiretinal membranes from PDR patients were studied by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot analysis.

Results: Vascular endothelial growth factor, OPG, and soluble RANK levels in vitreous samples from PDR patients were significantly higher than that in nondiabetic controls. Soluble TRAIL levels were significantly lower in PDR patients than that in nondiabetic control, whereas soluble RANKL levels did not differ significantly. RANKL, RANK, and TRAIL were expressed in vascular endothelial cells, myofibroblasts, and CD45-expressing leukocytes in PDR epiretinal membranes.

Conclusions: Dysregulated expression of OPG/RANKL/RANK pathway and TRAIL might be related to inflammation and angiogenesis in PDR.

Keywords:

• Osteoprotegerin
• proliferative diabetic retinopathy
• RANK ligand
• receptor activator of nuclear factor-κB (RANK)
• tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
• vitreous

Acknowledgments

The authors thank Ms. Kathleen van den Eynde and Mr. Wilfried Versin for technical assistance and Ms. Connie Unisa-Marfil for secretarial work.

Funding

This work was supported by King Saud University through Vice Deanship of Research Chair (Dr. Nasser Al-Rashid Research Chair in Ophthalmology, Abu El-Asrar AM) and the European Foundation for the Study of Diabetes (EFSD)/Sanofi Collaborative Programme 2015.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by King Saud University through Vice Deanship of Research Chair (Dr. Nasser Al-Rashid Research Chair in Ophthalmology, Abu El-Asrar AM) and the European Foundation for the Study of Diabetes (EFSD)/Sanofi Collaborative Programme 2015.