Effect of interleukin-1 blockers, CK112, and CK116 on rat experimental choroidal neovascularization in vivo and endothelial cell cultures in vitro.
OBJECTIVE
The aim of this study was to investigate the effect of interleukin-1 blockers, CK112 and CK116, on laser-induced experimental choroidal neovascularization (CNV) in rat models in vivo and endothelial cell proliferation in vitro.


METHODS
Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. CK112, CK116, and prednisolone were given once-daily through intraperitoneal (i.p.) injection after laser treatment for 4 weeks. The development of CNV was determined by fluorescein angiography performed on weeks 2 and 4. Human umbilical vein endothelial cells (HUVEC) were tested with proliferation assay with CK112, CK116, and prednisolone at different concentrations.


RESULTS
The intensity of fluorescein leakage from the photocoagulated lesions decreased significantly, compared to the control group (treated with dimethyl sulfoxide [DMSO] only), following CK112, CK116, and prednisolone treatment. Four (4) weeks after administration, CK112, at 10 mg/kg and 30 mg/kg, inhibited CNV development to 75% and 77% of the control group, respectively (P < 0.01). Both CK116, 10 mg/kg, and prednisolone, 5 mg/kg, inhibited the CNV development to 85% of the control group (P < 0.05). All three compounds interfered with the endothelial cell proliferation significantly. The reduction of the endothelial cells was 50.5% (P < 0.01), 28.5% (P < 0.05), and 23.1% (P < 0.05), respectively, in 500 microg/mL, 300 microg/mL, and 100 microg/mL of the CK112-treated group. CK116 inhibited the cell proliferation significantly to 77.2% of the control group at 500 microg/mL (P < 0.05).


CONCLUSIONS
CK112 and CK116 inhibited the development of CNV in the rat model and interfered with vascular endothelial cell proliferation in vitro. Our results suggest that CK112 and CK116 may be good candidates to inhibit ocular neovascularization related to age-related macular degeneration (ARMD).
Zou
Yanhong
Y
Institute of Ocular Pharmacology, Medical Pharmacology & Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843, USA.
Xu
Xinrong
X
Chiou
George C Y
GC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D005451:Fluorescein Angiography; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D014471:Umbilical Veins / Q000166:cytology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C510511:CK 112; C510512:CK 116; D005938:Glucocorticoids; D007375:Interleukin-1; D011724:Pyridazines; D011239:Prednisolone