Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy

Int J Mol Sci. 2020 Aug 28;21(17):6243. doi: 10.3390/ijms21176243.

Abstract

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.

Keywords: diabetes retinopathy (DR); electroretinography (ERG); fibroblast growth factor21 (FGF21); pemafibrate; selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα); streptozotocin (STZ); synaptophysin.

MeSH terms

  • Animals
  • Benzoxazoles / administration & dosage*
  • Benzoxazoles / pharmacology
  • Blood Glucose
  • Body Weight / drug effects
  • Butyrates / administration & dosage*
  • Butyrates / pharmacology
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Retinopathy / physiopathology
  • Diabetic Retinopathy / prevention & control*
  • Disease Models, Animal
  • Electroretinography
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation / drug effects
  • Lipid Metabolism
  • Liver Function Tests
  • Male
  • Mice
  • Retina / physiopathology*
  • Streptozocin
  • Synaptophysin / metabolism
  • Treatment Outcome

Substances

  • (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
  • Benzoxazoles
  • Blood Glucose
  • Butyrates
  • Synaptophysin
  • Syp protein, mouse
  • fibroblast growth factor 21
  • Streptozocin
  • Fibroblast Growth Factors