Cataract surgery induces retinal pro-inflammatory gene expression and protein secretion

Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):249-55. doi: 10.1167/iovs.10-6001.

Abstract

Purpose: To investigate the effect(s) of cataract surgery on the expression of pro-inflammatory genes and proteins in the retina using an experimental rodent model.

Methods: An extracapsular lens extraction was performed in one eye of C57BL/6 mice (n = 24); the contralateral unoperated eyes (n = 24) as well as eyes from unoperated animals (n = 9) served as controls. The neurosensory retina and retinal pigment epithelium (RPE)/choroid were collected postoperatively. Expression of genes involved in the acute inflammatory/injury response, including IL-1β, fibroblast growth factor, transforming growth factor β, chemokine CCL2, SDF-1, and complements C3, C4, and factor B (CFB), were examined by real-time PCR and, selectively, by immunohistochemistry.

Results: The expression of IL-1β and CCL2 genes was markedly upregulated (>20-fold, P < 0.01) in the neurosensory retina 30 minutes postoperatively and maintained for the 2-week postoperative period of observation; IL-1β expression was also upregulated in RPE/choroid. The expression of complement C3 (>5-fold) and CFB (>30-fold) genes in the neurosensory retina was also significantly upregulated (P < 0.01 in both cases). Increased IL-1b, CCL2, and CFB as well as enhanced C5b-9 immunostaining were observed by confocal microscopy.

Conclusions: In rodents, lens extraction elicited an acute pro-inflammatory gene and protein response in the posterior segment of the eye, indicating induction of the inflammasome as well as complement activation, as occurs in the "danger" response. A similar response in humans might explain the pathogenesis of cataract surgery-associated retinal complications such as cystoid macular edema.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cataract Extraction*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Choroid / immunology
  • Complement System Proteins / genetics*
  • Complement System Proteins / metabolism
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation / physiology*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Retina / immunology*
  • Retinal Pigment Epithelium / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • CXCL12 protein, human
  • Chemokine CCL2
  • Chemokine CXCL12
  • Cytokines
  • Interleukin-1beta
  • Transforming Growth Factor beta
  • Fibroblast Growth Factors
  • Complement System Proteins