The primary cause of AMD is not known, but several lines of investigation have been directed at elucidating the connection between BM aging and cellular changes seen in the disease, such as RPE atrophy and photoreceptor degeneration.
10,11,14,18,20 Age-related changes within BM occur several decades before cellular ones, thus suggesting that BM dysfunction can precede and may induce changes in surrounding cells.
14,15,19,20 In our system, previously developed to isolate the effects of basement membrane aging from the effects of cellular aging, we have shown that BM aging affects proper attachment and proliferation of RPE cells and increases their rate of apoptosis while decreasing the rate of phagocytosis.
27,28 We have also shown that reengineering human BM can improve the attachment, survival, and proliferation of the RPE.
27 In this report, we showed that reengineering of old donor–derived human BM with detergent cleaning, and subsequent recoating with ECM proteins, can increase the phagocytic ability of ARPE-19 cells cultured on its surface. However, this increase did not reach levels compared with young BM, indicating that other factors are also involved in the aging process and in the functional decrease in phagocytosis of cells cultured onto old BM. It is likely that other deleterious changes occur at the molecular level within BM as a function of age, such as other forms of enzymatic or nonenzymatic protein crosslinking (e.g., nonreducing sugars, reactive oxygen species, and reactive nitrogen species).
10 In addition, aging of BM may also affect other proteins (e.g., heparan sulfate) that may play an important role in the overall function of the RPE.
20 These results are not surprising, since the molecular changes that occur within BM with aging are protean in nature, and not completely understood. Nevertheless, the fact that there is an increase in proliferation, survival, and RPE function by providing fresh ECM protein may also be important in other systems designed to reproduce an artificial BM.
32 A recent report describes how primary RPE cells were able to grow and proliferate as polarized monolayers in three-dimensional scaffolds made of collagen type 1 and a material called poly(lactic-co-glycolic acid) (PLGA).
32 This fibrillary network resembles the fibrillar architecture of the collagenous layer of BM, and cells grow looking morphologically and molecularly similar to RPE while displaying a correctly polarized monolayer.
32 Additional coating of these scaffolds with ECM proteins may have a long-term positive impact in the overall function of transplanted RPE monolayers.