Macrophage Activation Pattern in Human Myopic Choroidal Neovascular Membranes

Abstract

 

Purpose

 

A little is known about the role of macrophages in myopic choroidal neovascular membrane (CNV) pathogenesis. The present study aimed to characterize the pattern of macrophage activation in CNV caused by degenerative myopia compared to that caused by age related macular degeneration (AMD).

 

Methods

 

20 surgically excised CNV derived from 15 AMD (5 classic and 10 occult CNV) patient and 5 patient with degenerative myopia were stained using CD68, CCR7 and CD163 antibodies staining for pan macrophages, classically activated macrophage (M1 macrophages) and alternatively activated macrophage (M2 macrophages); respectively. The immunopositive cell density was calculated per mm2 in 400x images.

 

Results

 

All CNVs were untreated and subfoveally located. Macrophage infiltration was higher in the myopic CNV with a cell density of M: 268.4±117.78; M1: 137.8 ±189.5; M2: 453.6±313 cell/mm2. In classic AMD related CNV, the cell density of M macrophages were 251.6±72.8 cell /mm2, M1 macrophages: 131.4± 94.38, and M2 macrophages: 122.8±64.10 cell/mm2. In occult AMD related CNV, the cell density of M macrophages were 301± 159 cell /mm2, M1 macrophages: 167 ± 90 cell/mm2 and M2:167 ± 89 cell/mm2. Alternatively activated macrophages were the dominant type in myopic CNV (p value: 0.043) and differ significantly from both classic and occult AMD CNV, (p value: 0.008, 0.01) respectively.

 

Conclusions

 

Alternatively activated macrophages might play an important role in the myopic CNV pathogenesis. The identification of different activation patterns may be important for distinct therapeutic strategies.

 

 

Fig. 1 Macrophage polarized activation. A simplified view of immune and tissue-derived signals inducing classical (M1) and alternative (M2) macrophage polarized activation. The main functional effects on macrophage functions, molecular markers and effector molecules are schematically represented in both cases.

 

 

Fig. 2 Immunohistochemical detection of macrophage phenotypes (M1 and M2). A) Photomicrographs of myopic CNV depicting CD 163 (M2) positive macrophages (black arrow). Vascular channels are seen within the fibrous part of the membrane. B) Photomicrographs of occult CNV depicting CCR7 (M1) positive macrophages (black arrow),in close relation to RPE cells, scale bare 20µm.

 

Keywords: 605 myopia • 453 choroid: neovascularization • 638 pathology: human