Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula

J Comp Neurol. 2017 Sep 1;525(13):2890-2914. doi: 10.1002/cne.24245. Epub 2017 Jun 7.

Abstract

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases.

Keywords: Meriones shawi; RRID: AB_10000347; RRID: AB_11210186; RRID: AB_11212299; RRID: AB_11214092; RRID: AB_177456; RRID: AB_2167511; RRID: AB_2201526; RRID: AB_2298772; RRID: AB_477010; RRID: AB_477329; RRID: AB_628142; RRID: AB_839504; RRID: AB_882426; RRID: AB_94843; diabetic macular edema; diabetic retinopathy; high fat diet; neurodegeneration; type 2 diabetes; visual streak.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Diabetic Retinopathy / complications*
  • Disease Models, Animal
  • Gerbillinae
  • Macular Degeneration / etiology*
  • Macular Degeneration / pathology
  • Male
  • Microfilament Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Opsins / metabolism
  • Retina / metabolism
  • Retina / pathology*
  • Retinal Degeneration / etiology*
  • Retinal Degeneration / pathology
  • Rhodopsin / metabolism
  • Transcription Factor Brn-3A / metabolism
  • cis-trans-Isomerases / metabolism

Substances

  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Opsins
  • Transcription Factor Brn-3A
  • Rhodopsin
  • retinoid isomerohydrolase
  • cis-trans-Isomerases