Oil red O staining suggests that the rounded particles of tryptase immunoreactivity in GA choroid might be low density lipoprotein (LDL) deposited in BM, RPE, and drusen. The accumulation of lipids as a consequence of aging and AMD has been well characterized by Curcio et al.
17–20 There is considerable indirect evidence suggesting a connection between lipid deposition/oxidation and aging diseases, such as AMD. Accumulation of oxidized lipids in RPE, BM, and CH in the aging eye impedes the proper flow of nutrients and metabolites. It also is a likely cause of chronic inflammation. It has been demonstrated that LDL binds to released MC granules and forms complexes.
21 Heparan, which is stored in complex with tryptase in the secretory granule and cosecreted during degranulation, is essential for binding of LDL to granules.
22,23 Tryptase is a unique serine protease that is active enzymatically only in its tetrameric form.
24 It requires glycosaminoglycans (GAGs), notably heparan proteoglycan of MCs, for preservation of its enzymatic activity.
25 The heparan proteoglycans tend to prevent monomerization of the enzyme after secretion, preserving its activity for a prolonged period of time in the extracellular space. In addition to the fibrous connective tissue elements present in BM, a variety of proteoglycans also are found in this compartment. The major proteoglycans present are the chondroitin sulfate, dermatan sulfate, and heparan sulfate-types.
26 In addition, the nonsulfated glycosaminoglycan, hyaluronic acid also is present in this compartment. With age, there is an increase in proteoglycans in BM.
27 Proteoglycans have a well-established role of retaining LDLs early in the pathogenesis of atherosclerosis.
28 Like MC–derived heparan proteoglycans, the arterial proteoglycans also can stabilize the tryptase tetramer or may modulate the activity of tryptase. Degranulated MCs present in atherosclerotic lesions release tryptase and the released tryptase is stabilized by arterial proteoglycans.
3 Taken together, the accumulation of LDL and increased proteoglycans within BM with age
29,30 may act in concert to bind and stabilize secreted MC tryptase and to preserve the enzymatic activity in this structure for prolonged periods.