Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury.
Previously, thymosin beta 4 (Tbeta(4)) was found to promote wound healing in full thickness skin wounds and heptanol debrided corneas. Here, the effect of Tbeta(4) was examined treatment on corneal wound healing and inflammation in vivo after alkali injury, a more severe wound of the eye. Corneas from 129 Sv mice were chemically burned with a 2 mm disc soaked in 1 N NaOH for 30 sec. Eyes were irrigated copiously with phosphate buffered saline (PBS) and then treated topically with either Tbeta(4) (5 microg/5 microl PBS) or 5 microl PBS twice daily. Animals were killed, the eyes were enucleated, fixed and embedded in plastic resin or prepared for mRNA analysis. Mouse corneas topically treated with 5 microg of Tbeta(4) twice daily after alkali injury demonstrated accelerated re-epithelialization at all time points and decreased polymorphonuclear leukocyte (PMN) infiltration at 7 days post injury (p.i.) when compared to PBS-treated controls. mRNA transcript levels were decreased several fold for interleukin (IL)-lbeta, and the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2 and monocyte chemoattractant protein (MCP)-1 from 1 to 7 days after injury in the Tbeta(4)- vs. PBS-treated corneas. Thus, Tbeta(4) may provide a new clinical treatment for severe traumatic corneal wound disorders by promoting rapid corneal wound healing and decreasing both PMN infiltration and inflammatory cytokine and chemokine mRNA levels.
Sosne
Gabriel
G
Eye Care Services Department, Henry Ford Hospital, 2799 West Grand Boulevard K10, Detroit, MI 48202, U.S.A. asosne@hotmail.com
Szliter
Elizabeth A
EA
Barrett
Ronald
R
Kernacki
Karen A
KA
Kleinman
Hynda
H
Hazlett
Linda D
LD
D000287:Administration, Topical; D000468:Alkalies; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002057:Burns, Chemical / Q000188:drug therapy* / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D003315:Cornea / Q000276:immunology / Q000648:ultrastructure; D065306:Corneal Injuries; D005126:Eye Burns / Q000188:drug therapy* / Q000276:immunology; D007375:Interleukin-1 / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000235:genetics; D013947:Thymosin / Q000627:therapeutic use*; D013997:Time Factors; D014945:Wound Healing / Q000276:immunology*; D000099201:Thymosin beta(4)
D000468:Alkalies; D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D013947:Thymosin; D000099201:Thymosin beta(4); C404915:Cxcl2 protein, mouse