Are low inflammatory reactions involved in exudative age-related macular degeneration? Morphological and immunhistochemical analysis of AMD associated with basal deposits.
OBJECTIVE
Basal laminar and linear deposits (BLD) are associated with the development of choroidal neovascularization (CNV). Therefore, analysis of BLD composition may provide further information concerning the pathogenesis of BLD and CNV in age-related macular degeneration (AMD).


METHODS
BLD in 25 specimens of surgically removed CNV were examined, using histochemical and immunohistochemical methods, for extracellular matrix proteins and their modulating enzymes, and for cell markers and proteins involved in inflammatory processes. In addition, ultrastructural electron microscopic analysis (EM) was performed.


RESULTS
The chemical and structural composition of all the BLD was similar. Only the inner aspect of the BLD contained laminin and collagen IV, which corresponded to a new RPE basal lamina upon EM analysis. The extracellular matrix protein predominantly found in all layers of BLD was vitronectin, which was seen as a homogeneous material within the BLD upon EM analysis. The metalloproteinases MMP-2 and MMP-9 could only be detected in the inner aspect, while MMP-7 and TIMP-3 were observed predominantly in the outer aspect of BLD. In this area, staining for phospholipids and less intensely for neutral lipids was also visible. The labelling of complement complexes C3 and C5b-9 was intensely positive, and vascular endothelial growth factor (VEGF) was detected in all BLDs.


CONCLUSIONS
Diffuse deposits such as BLD appear consistently with the development of CNV in AMD. They consist of extracellular matrix components and predominantly vitronectin. However, activated complement and VEGF could also be detected. The results of the current study may support the hypothesis that inflammatory processes are involved in the pathogenesis of BLD and CNV in AMD.
Lommatzsch
A
A
Department of Ophthalmology and Ophtha-Lab, St. Franziskus Hospital Münster, Münster, Germany. Albrecht.Lommatzsch@web.de
Hermans
P
P
Müller
K D
KD
Bornfeld
N
N
Bird
A C
AC
Pauleikhoff
D
D
D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure*; D015415:Biomarkers / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003176:Complement C3 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005122:Exudates and Transudates; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000032:analysis; D008268:Macular Degeneration / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
D015415:Biomarkers; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D016326:Extracellular Matrix Proteins; D008055:Lipids; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D053505:Matrix Metalloproteinases, Secreted