Impaired Rhodopsin Generation in the Rat Model of Diabetic Retinopathy

Am J Pathol. 2017 Oct;187(10):2222-2231. doi: 10.1016/j.ajpath.2017.06.007. Epub 2017 Jul 19.


Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity, and color perception before microvascular pathologies become apparent. Herein, we evaluated early changes in neural retinal function and in retinoid metabolism in the eye in diabetes. Streptozotocin-induced diabetic rats showed decreased a- and b-wave amplitudes of scotopic and photopic electroretinography responses 4 months after diabetes induction compared to nondiabetic controls. Although Western blot analysis revealed no difference in opsin expression, rhodopsin content was decreased in diabetic retinas, as shown by a difference in absorbance. Consistently, levels of 11-cis-retinal, the chromophore for visual pigments, were significantly lower in diabetic retinas compared to those in controls, suggesting a retinoid deficiency. Among visual cycle proteins, interphotoreceptor retinoid-binding protein and stimulated by retinoic acid 6 protein showed significantly lower levels in diabetic rats than those in nondiabetic controls. Similarly, serum levels of retinol-binding protein 4 and retinoids were significantly lower in diabetic rats. Overall, these results suggest that retinoid metabolism in the eye is impaired in type 1 diabetes, which leads to deficient generation of visual pigments and neural retinal dysfunction in early diabetes.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology*
  • Disease Models, Animal
  • Male
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology
  • Rats, Wistar
  • Retina / pathology
  • Retina / physiopathology
  • Retinaldehyde / metabolism
  • Retinol-Binding Proteins, Plasma / metabolism
  • Rhodopsin / metabolism*
  • Visual Pathways / metabolism
  • Visual Pathways / pathology


  • Rbp4 protein, rat
  • Retinol-Binding Proteins, Plasma
  • Rhodopsin
  • Retinaldehyde