Increased expression of chemokine KC, an interleukin-8 homologue, in a model of oxygen-induced retinopathy

Curr Eye Res. 2005 Apr;30(4):299-307. doi: 10.1080/02713680590923276.

Abstract

Purpose: The purpose of this study was to determine the retinal expression of angiogenic chemokines/cytokines in a mouse model of oxygen-induced retinopathy.

Methods: C57BL/6 (B6) mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12 and then recovered in room air. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine relative mRNA levels of KC, macrophage inflammatory protein-2 (MIP-2), interleukin-1alpha (IL-1alpha), and interferon gamma (IFN-gamma). Immunohistochemistry was used to localize KC in the retina. IL-1alpha was also injected into the vitreous of mouse eyes, and KC expression was examined by RT-PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry.

Results: KC expression at both the mRNA and protein levels was increased in P14, P17, and P21 of hyperoxia-injured eyes. KC immunoreactivity was localized along the nerve fiber layer and in radial Müller cell processes. IL-1alpha mRNA was modestly increased in hyperoxia-injured eyes on P14 and P17. INF-gamma mRNA was not detected in the retina. Adult mouse eyes injected with IL-1alpha demonstrated increased levels of both KC mRNA and protein, with KC immunoreactivity localized to Müller cell processes.

Conclusions: Oxygen-induced injury to the developing retina results in the induction of the CXC chemokine KC at both the mRNA and protein levels during the peak time points of neovascularization, suggesting a possible role in the pathogenesis of retinopathy of prematurity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines / genetics
  • Chemokines / metabolism
  • Chemokines, CXC / genetics*
  • Chemokines, CXC / metabolism*
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Hyperoxia / complications
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Oxygen / toxicity
  • RNA, Messenger / metabolism
  • Retinal Neovascularization / etiology
  • Retinal Neovascularization / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines
  • Chemokines, CXC
  • Cxcl1 protein, mouse
  • Cxcl2 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1
  • Interleukin-8
  • RNA, Messenger
  • Interferon-gamma
  • Oxygen