Purpose: 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 µg/mL,
300 µg/mL, and 100 µg/mL of the CK112-treated group. CK116 inhibited the cell proliferation significantly to 77.2% of the control group at 500 µg/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).
