Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization.
OBJECTIVE
To determine the expression of angiogenic cytokines in macrophages and retinal pigment epithelium cells in choroidal neovascularization (CNV).


METHODS
Ten surgically-excised subfoveal CNV specimens and ten eye bank eyes with subfoveal CNV were routinely processed, serially sectioned, and immunostained for factor VIII (F8), CD68 (KP1), cytokeratin 18 (CK18), vascular endothelial growth factor (VEGF), tissue factor (TF), and monocyte chemotactic protein (MCP). The CNV was classified as "inflammatory active" (more inflammation than fibrosis) or "inflammatory inactive" (morefibrosis than inflammation). The immunostaining was graded as none, mild (+), moderate (++), or heavy (+++). Five additional surgically-excised CNV specimens were dual labeled with CK18/MCP or CD68/TF and confocal scanning laser microscopy was performed.


RESULTS
Vascular endothelium, macrophages, and RPE expressed F8, KP1, and CK18 respectively. Macrophages expressed + to ++ VEGF and ++ to +++ TF; RPE expressed ++ to +++ VEGF and ++ to +++ MCP. Staining for angiogenic cytokines was stronger in inflammatory active versus inflammatory inactive CNV. RPE dual labeled for CK18/MCP and macrophages dual labeled for CD68/TF.


CONCLUSIONS
This study shows that RPE cells express MCP, a cytokine involved with macrophage recruitment, and that macrophages express TF in CNV. Macrophages and RPE express VEGF, thus perpetuating angiogenesis. TF is involved with fibrin formation and provides a scaffold effect for growth of the CNV complex. CNV likely represents a dynamic process with inflammatory active and inflammatory inactive (involutional) stages.
Grossniklaus
Hans E
HE
Departments of Ophthalmology and Pathology, Emory University School of Medicine, Atlanta, GA, USA. ophtheg@emory.edu
Ling
Jun X
JX
Wallace
Timothy M
TM
Dithmar
Stefan
S
Lawson
Diane H
DH
Cohen
Cynthia
C
Elner
Victor M
VM
Elner
Susan G
SG
Sternberg
Paul
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D013925:Thromboplastin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D016228:Endothelial Growth Factors; D005169:Factor VIII; D007633:Keratins; D008222:Lymphokines; D018945:Monocyte Chemoattractant Proteins; D013925:Thromboplastin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule