Angiotensin type-1 receptor inhibition is neuroprotective to amacrine cells in a rat model of retinopathy of prematurity

J Comp Neurol. 2010 Jan 1;518(1):41-63. doi: 10.1002/cne.22205.

Abstract

Retinopathy of prematurity (ROP) is characterized by deficits in the scotopic pathway, although the cellular locus for these deficits is not clear. Here we examined neurochemical and cellular changes that develop during oxygen-induced retinopathy, a model of ROP. In addition, we examined whether treatment with the angiotensin II type-1 receptor inhibitor, valsartan, prevented these changes. Newborn Sprague-Dawley rats were exposed from postnatal day (P) 0 to 11 to 80%:20% O(2) (22:2 hr/day) and then room air until P18. Valsartan (40 mg/kg/day) was administered from P12-P18. Pattern recognition analysis of overlapping amino acid profiles was used to provide a statistically robust and spatially complete classification of neural elements for each experimental condition. Classification yielded 12 neuronal theme classes in controls and nine classes following ROP. ROP was associated with a reduction in the number of amacrine and bipolar cell theme classes. The reduction in theme classes was confirmed as true neuronal loss by quantifying anatomical changes and using an apoptotic marker. ROP was associated with shifts in amino acid levels across all neuronal populations except for horizontal cells. A reduction in the density of glycine-immunoreactive amacrine cells, and particularly parvalbumin-immunoreactive AII amacrine cells, was observed following ROP. Valsartan treatment during ROP prevented loss of theme classes and loss of AII amacrine cells. This study suggests that deficits in scotopic vision during ROP may be associated with loss of AII amacrine cells. In addition, this study highlights the potential of AT(1)R blockade in preventing neuronal anomalies in this condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells* / drug effects
  • Amacrine Cells* / metabolism
  • Amacrine Cells* / pathology
  • Amino Acids / metabolism
  • Angiotensin II Type 1 Receptor Blockers* / metabolism
  • Angiotensin II Type 1 Receptor Blockers* / pharmacology
  • Animals
  • Animals, Newborn
  • Color Vision / physiology
  • Glycine / metabolism
  • Humans
  • Infant, Newborn
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Receptor, Angiotensin, Type 2 / metabolism
  • Retina / chemistry
  • Retina / cytology*
  • Retina / drug effects*
  • Retina / pathology*
  • Retinopathy of Prematurity* / metabolism
  • Retinopathy of Prematurity* / pathology
  • Tetrazoles / metabolism
  • Tetrazoles / pharmacology
  • Valine / analogs & derivatives
  • Valine / metabolism
  • Valine / pharmacology
  • Valsartan
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amino Acids
  • Angiotensin II Type 1 Receptor Blockers
  • Neuroprotective Agents
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Tetrazoles
  • gamma-Aminobutyric Acid
  • Valsartan
  • Valine
  • Glycine