Protein analysis of human maculae in relation to age-related maculopathy.

Age-related maculopathy (ARM) is the most common cause of blindness in the elderly in the western world. Its early stage is characterized by many histopathologic changes, including two extracellular deposits, basal laminar deposit (BLD) and drusen. The origin and chemical composition of BLD and drusen are unknown and are considered to be important in the development of ARM, so we analyzed proteins in human macular tissue associated with ARM. Homogenized macular extracts of 15 human eyes with ARM and 10 age-matched control eyes were examined by two-dimensional electrophoresis. The proteins in the gels were silver-stained, and the obtained protein patterns were analyzed by a computer-imaging system. Five glycoproteins were specifically present in human maculae with ARM (p = 0.0009). One of the spots was characterized by sequence analysis as haptoglobin beta-chain, and another had a high homology with a part of the interphotoreceptor retinoid-binding protein precursor. However, the 100% matching of the latter was not statistically significant because we could only sequence eight amino acids of this protein. The known association between haptoglobin beta-chain and atherosclerosis and the increase of this glycoprotein in human maculae with ARM supports the recently described relationship between atherosclerosis and ARM found in an epidemiologic study. Furthermore, the neovascular growth-stimulating properties of haptoglobin warrant further research into haptoglobin as a possible inducing agent of late stages of ARM.