Effects of interleukin-1 blockers on corneal fibroblast proliferation in vitro and ocular inflammation in vivo.
The success of keratorefractive surgical procedures is limited by the wound healing process in the corneal stroma. The proliferation and matrix synthesis of corneal stromal fibroblasts is the central element of the wound healing process that is triggered by an initial inflammation. In order to develop new therapeutic strategies to reduce wound healing intensity, we investigated the effect of newly synthesized interleukin-1 (IL-1) blockers on the proliferation of cultured rabbit corneal fibroblasts and the ocular inflammation induced by IL-1. It was found that the addition of IL-1 blockers, such as CK-135 to CK-145, led to a dose-dependent inhibition of cell proliferation after 24, 48 and 72 hr of incubation. The isotope incorporation study showed that the syntheses ofDNA and mRNA were suppressed whereas that of protein was enhanced or unaffected. These compounds also demonstrated a potent anti-inflammation action in the rat uveitis model. Our results indicate that CK (Chiou-Kumamoto) compounds may be valuable therapeutic agents for the prevention of postoperative complications after corneal keratorefractive surgical procedures.
Liu
Q
Q
Institute of Ocular Pharmacology and Department of Medical Pharmacology and Toxicology, Texas A&M University System Health Science Center, College Station 77843-1114, USA.
Zhou
Y H
YH
Xuan
B
B
Chiou
G C
GC
Okawara
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003316:Corneal Diseases / Q000188:drug therapy*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005128:Eye Diseases / Q000188:drug therapy*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007375:Interleukin-1 / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D007930:Leucine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014529:Uridine / Q000378:metabolism
D007375:Interleukin-1; D011506:Proteins; D012333:RNA, Messenger; D004247:DNA; D007930:Leucine; D013936:Thymidine; D014529:Uridine