Effects of arteriolar constriction on retinal gene expression and Müller cell responses in a rat model of branch retinal vein occlusion

Graefes Arch Clin Exp Ophthalmol. 2014 Feb;252(2):257-65. doi: 10.1007/s00417-013-2532-z. Epub 2013 Nov 29.

Abstract

Background: To investigate the effect of induced arteriolar constriction (AC) on alterations in gene expression of factors implicated in the development of edema in branch retinal vein occlusion (BRVO).

Methods: In Brown-Norway rats, BRVO was induced by laser photocoagulation of the veins in one half of the retina. AC of the afferent arterioles was performed 30 min later. We then determined the expression of Vegfa, Vegfb, Pedf, Kir4.1, Aqp4, Aqp1, Il1ß, and Il6 with real-time polymerase chain reaction (RT-PCR) in the neuroretina and retinal pigment epithelium (RPE) after 1, 3, and 7 days. Immunostaining against GFAP, aquaporin (AQP)-4, and Kir4.1 was performed on days 1 and 3.

Results: BRVO resulted in transient upregulation of Vegfa in the neuroretina on day 1. The expressions of Kir4.1, AQP4, and AQP1 were downregulated, and Il1ß and Il6 were strongly upregulated, on days 1 and 3. The retinal distribution of GFAP and AQP4 proteins remained unaltered, while the Kir4.1 protein displayed redistribution from polarized to uniform retinal distribution. AC accelerated the restoration of downregulated Kir4.1, Aqp4, and Aqp1 in the RPE, of Kir4.1 in the neuroretina, and of upregulated Il6 in the neuroretina. AC did not influence the gliotic alterations of Müller cells and the redistribution of the Kir4.1 protein.

Conclusion: Constriction of the afferent artery in the BRVO region accelerated the restoration of potassium channels and Il6. These alterations may contribute to faster resorption of retinal edema, and may decrease the level of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporins / genetics
  • Arterioles
  • Constriction, Pathologic
  • Disease Models, Animal*
  • Ependymoglial Cells / metabolism*
  • Eye Proteins / genetics*
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Interleukins / genetics
  • Macular Edema
  • Microscopy, Confocal
  • Potassium Channels, Inwardly Rectifying / genetics
  • Rats
  • Rats, Inbred BN
  • Real-Time Polymerase Chain Reaction
  • Retinal Artery / physiopathology*
  • Retinal Vein Occlusion / genetics*
  • Up-Regulation
  • Vascular Endothelial Growth Factors / genetics

Substances

  • Aquaporins
  • Eye Proteins
  • Glial Fibrillary Acidic Protein
  • Interleukins
  • Kcnj10 (channel)
  • Potassium Channels, Inwardly Rectifying
  • Vascular Endothelial Growth Factors