Article

Diabetologia

, Volume 52, Issue 12, pp 2633-2641

First online:

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

  • M. Garcia-RamírezAffiliated withCIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM), Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron
  • , C. HernándezAffiliated withCIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM), Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron
  • , M. VillarroelAffiliated withCIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM), Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron
  • , F. CanalsAffiliated withProteomics Laboratory, Medical Oncology Research Program, Institut de Recerca, Hospital Universitari Vall d’Hebron
  • , M. A. AlonsoAffiliated withDepartment of Ophthalmology, Hospital de Son Llàtzer
  • , R. FortunyAffiliated withDepartment of Biochemistry, Hospital de Son Llàtzer
  • , L. MasmiquelAffiliated withEndocrinology Service, Hospital de Son Llàtzer
  • , A. NavarroAffiliated withBlood and Tissue Bank, Hospital Universitari Vall d’Hebron
  • , J. García-ArumíAffiliated withService of Ophthalmology, Hospital Universitari Vall d’Hebron
    • , R. SimóAffiliated withCIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM), Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron Email author 

Abstract

Aims/hypothesis

Interphotoreceptor retinoid-binding protein (IRBP) plays a major role in the visual cycle and is essential to the maintenance of photoreceptors. The aim of this study was to determine whether a decrease in IRBP production exists in the early stages of diabetic retinopathy.

Methods

Vitreous samples from diabetic patients with proliferative and non-proliferative diabetic retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole (control group) were selected for IRBP quantitative assessment by proteomic analysis (fluorescence-based difference gel electrophoresis) and western blot. Human post mortem eyes (n = 16) from diabetic donors without clinically detectable retinopathy and from non-diabetic donors (n = 16) were used to determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content (western blot and confocal microscopy). Retinal neurodegeneration was assessed by measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human retinoblastoma cells were used to test the effects of glucose, TNF-α and IL-1β on IRBP expression and IRBP levels.

Results

Intravitreous IRBP concentration was significantly lower in PDR < NPDR < control in proteomic and western blot analysis. IRBP mRNA levels and IRBP protein content were significantly lower in the retinas from diabetic donors than in those from non-diabetic donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with non-diabetic retinas. A dose-dependent downregulation of IRBP mRNA expression and IRBP content was detected with glucose, TNF-α and IL-1β in cultures of Y79 human retinoblastoma cells.

Conclusions/interpretation

Underproduction of IRBP is an early event in the human diabetic retina and is associated with retinal neurodegeneration. The mechanisms leading to this deficit deserve further investigation.

Keywords

Diabetic retinopathy Human study Interphotoreceptor retinoid-binding protein Neurodegeneration Retina Vitreous fluid