Selective accumulation of the complement membrane attack complex in aging choriocapillaris.

Area of Science:

• Ophthalmology
• Immunology
• Pathology

Background:

• The complement membrane attack complex (MAC) is elevated in the choriocapillaris during aging and age-related macular degeneration (AMD).
• Perivascular MAC accumulation in the choroid is known, but its presence in other aging tissues is unclear.

Purpose of the Study:

• To investigate the abundance and localization of MAC across various human tissues.
• To determine if MAC deposition is unique to the ocular tissues affected by AMD.

Main Methods:

• Immunohistochemical labeling of paraffin-embedded human donor eyes (n=6) and a 19-tissue array.
• Antibodies used: anti-MAC, anti-intercellular adhesion molecule-1 (ICAM-1), and Ulex europaeus agglutinin-I (UEA-I).
• Confirmation using unfixed frozen sections of RPE-choroid and extraocular tissues.

Main Results:

• High MAC levels were exclusively detected in the choriocapillaris.
• MAC was not found in 38 additional samples from 19 diverse human tissues.
• ICAM-1 was widespread, and UEA-I labeled vasculature in all tissues examined.

Conclusions:

• MAC accumulation is highly restricted to the choriocapillaris.
• This ocular specificity of MAC may contribute to the targeted pathology of AMD in the retina, RPE, and choroid.
• The limited systemic distribution of MAC suggests a reason for the relative absence of systemic disease in AMD.