Abstract
Purpose: :
Pentraxin-2 (PTX-2) or serum amyloid P (SAP), is a circulating 125 kD member of the pentraxin family and a soluble pattern recognition receptor that modulates the behavior of monocytes/macrophages and thus their participation in innate immune responses to injury. In several models of organ injury, PTX-2 was shown to significantly reduce inflammation and fibrosis through suppression of monocyte-derived cells. In this study, we investigated the effects of PRM-151, a recombinant human PTX-2, in mice with laser-induced CNV and ischemia-induced RNV.
Methods: :
The effects of intraocular, intraperitoneal, and periocular injections of PRM-151 on CNV and RNV (measured in mm2) was investigated.
Results: :
Intraocular injection of 1µl (20µg/µl) PRM-151 at the time of rupture of Bruch’s membrane, and 5 and 9 days after laser resulted in an 80% reduction in CNV area (0.004491± 0.000648) compared to vehicle-injected eyes (0.022391±0.008779). Periocular injections of 3 µl (20 µg/µl) of PRM-151, given on days 0, 2, 4, 6, 8, 10 and 12 after laser did not cause a statistically significant reduction in CNV size compared to vehicle-injected eyes (0.020755±0.002855 and 0.018372±0.002090, respectively), but intraperitoneal injections of 80 µl (1 µg/µl) of PRM-151 (0.013132±0.001372) at the same time points caused a 56% reduction in CNV area (0.022562±0.003021). Intraocular injection of 1µl (20 µg/µl) of PRM-151 in mice with oxygen-induced ischemic retinopathy resulted in an 80% reduction in RNV area (0.094335±0.032224) compared to vehicle-injected eyes (0.450305±0.087299). Immunofluorescent staining for CXCR4 showed that intraocular injection of PRM-151 (43.8888±2.7910) reduced the number of bone marrow-derived cells in eyes with ischemia-induced RNV compared to control (77.2777± 3.8346).
Conclusions: :
Intraperitoneal or intraocular injections of PRM-151 suppresses CNV and intraocular injections of PRM-151 suppresses ischemia-induced RNV and reduces influx of bone marrow-derived cells.
Keywords: choroid: neovascularization • retinal neovascularization