Abstract
Purpose :
Interphotoreceptor retinoid-binding protein (IRBP) is an essential photoreceptor-specific protein responsible for the solubilisation and transport of retinoids between the retinal pigment epithelium and photoreceptors in the eye. Functional IRBP is critical for the survival of photoreceptors. We previously found that photoreceptor degeneration is preceded by a marked reduction of IRBP expression in a murine model of retinal degeneration. We believe this pathogenic progress occurs in most types of retinal stress such as that induced by hyperglycemia (diabetes). Therefore, we studied the dysregulation of IRBP under hyperglycemic conditions, both ex vivoand in vivo.
Methods :
We compared the retinal expression level of IRBP in Akita mice (a model of diabetes) to control C57bl/6 mice using Western blot. The location and intensity of IRBP expression was determined by immunofluorescence staining on frozen sections of the Akita and control mice. We further evaluated expression levels of IRBP in human retinal explants cultured with different concentrations of glucose.
Results :
There was significant down-regulation of IRBP (83% of the control level) in the retinas of Akita mice compared with those from C57bl/6 control mice. Immunofluorescent staining revealed that IRBP was primarily down-regulated in the inner and outer segments of the retinas of the Akita mice when compared with retinas of control mice. This down regulation was also observed in the human retinal explants cultured with high concentrations of glucose. A high glucose treatment (45mM D-Glucose) significantly reduced the expression of IRBP (49% of the control level) compared with the control treatment (5.5mM D-Glucose).
Conclusions :
Hyperglycemia induces the down-regulation of IRBP expression in photoreceptors of mice and the human retina. This may contribute to the pathogenesis of diabetic retinopathy. Further studies of signaling pathways which regulate the expression of IRBP under hyperglycemic conditions are needed to affirm this hypothesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.