Increased expression of chemokine KC, an interleukin-8 homologue, in a model of oxygen-induced retinopathy.
OBJECTIVE
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.
Powers
Michael R
MR
Department of Pediatrics, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA. powersm@ohsu.edu
Davies
Michael H
MH
Eubanks
Joshua P
JP
D000818:Animals; D000831:Animals, Newborn; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D018496:Hyperoxia / Q000150:complications; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D007371:Interferon-gamma; D010100:Oxygen