Microglial ramification and redistribution concomitant with the attenuation of choroidal neovascularization by neuroprotectin D1.
OBJECTIVE
Neuroprotectin D1 (NPD1) attenuates laser-induced choroidal neovascularization (CNV) when administered intraperitoneally. Due to its lipophilicity and low molecular weight, NPD1 is well suited for topical delivery; thus, we investigated the efficacy of topically applied NPD1 in attenuating CNV. We also examined the effect of NPD1 on the recruitment and activation of microglia surrounding CNV lesions.


METHODS
Mice were given laser-induced CNV and treated with NPD1 eye drops. CNV was evaluated by fluorescein leakage using a novel image analysis method and by isolectin B4 immunofluorescence of neovasculature. Microglia; recruitment was assessed by quantification. Using form factor, solidity, convexity, and fractal dimension, microglial activation was quantitatively assessed by two-dimensional, and for the first time, three-dimensional morphology. An ImageJ plugin, 3D Shape, was developed to enable this analysis.


RESULTS
NPD1 attenuated leakage and neovascularization. The proximity of microglia to CNV lesions was significantly closer with NPD1. Consistent with the cellular ramification, microglia in NPD1-treated eyes were larger and exhibited a lower form factor and higher fractal dimension.


CONCLUSIONS
Our data show that NPD1 signaling induces a ramified, non-injury-inducing microglial phenotype coincident with attenuation of CNV. Since microglia are crucial participants in neurodegenerative diseases, the discovery that microglia are potential targets of NPD1 signaling warrants further investigation.
Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA, USA.
Kristopher G
KG
Sheets
Bokkyoo
B
Jun
Yongdong
Y
Zhou
Min
M
Zhu
Nicos A
NA
Petasis
William C
WC
Gordon
Nicolas G
NG
Bazan
D000287:Administration, Topical; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005451:Fluorescein Angiography; D007834:Lasers; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D011859:Radiography
C487679:protectin D1; D004281:Docosahexaenoic Acids