Lipid Accumulation in Aging Bruch's Membrane

Public Deposited

Age-related maculopathy (ARM) is a leading cause of legal blindness in the elderly in the world. Currently, the physiological and ultrastructural bases for the development of ARM remain unclear. Many studies have proposed that the morphological changes, particularly the accumulations of lipids with aging, in Bruch's membrane - an extracellular matrix between the retinal pigment epithelium (RPE) and the choriocapillaris, are likely to impede the metabolite transport across this region thus lead to the dysfunction of the RPE and photoreceptor cells. However, this age-related phenomenon is not fully understood, as many conventional tissue processing techniques do not preserve lipids in the tissue very well In this study, lipid-preserved quick-freeze/deep-etch (QFDE) technique and stereologic methods are used to characterize, both qualitatively and quantitatively, the age-related accumulations of lipids in Bruch's membrane. We find solid lipid particles that we called "lipoprotein-like particles (LLPs)" as the major debris accumulated in Bruch's membrane. It appears that, with the increase of age, significant amount of LLPs are accumulated and filled the middle of Bruch's membrane, which in turn promotes further LLP accumulation into the inner aspect of the tissue and leads to the formation of a lipid wall adjacent to the basal lamina of the RPE; while no further LLP accumulation is seen in the outer aspect of Bruch's membrane. This pattern suggests a potential RPE source for the LLPs observed in Bruch's membrane We further evaluate the total lipid content of the LLPs in macular Bruch's membrane by incorporating the information of the LLP volume fraction with the dimensions of the tissue. The LLP-associated lipid content in Bruch's membrane appears to increase with age, and resembles the total lipid amount in the tissue measured by Holz et al. (1994). Hence the LLPs are likely to account for a large fraction of the age-related lipid accumulations in the tissue The mechanism of the transport of the LLPs across Bruch's membrane is unclear, as these particles appear to be much larger than the interfibril spacing in the outer bound of tissue. By using an in vitro model system, we demonstrate that lipid particles with their size larger than the interfibril spacing can be carried through Bruch's membrane by a flow. Thus it is probable that the LLPs squeeze through the interfibril spacing in Bruch's membrane

Last modified
  • 08/06/2018
Date created
Resource type
Rights statement