Changes in Bruch’s membrane and related structures with age

Abstract

Age-related macular disease is a major and growing public health burden in developed Caucasian societies, accounting for about 50% of blind registration. Evidence exists that this is an emerging problem in Eastern Asia, although the phenotype appears to differ from that seen in Western society. It is likely that several genes are involved, and that the genes or allelic variants conferring are common. Environment plays a major role in its pathogenesis, and it is believed that genetic susceptibility becomes apparent only if there are sufficient environmental pressures. There is no therapy currently available that will have an impact on the prevalence of blindness from age-related macular disease. It has been shown that visual loss occurs as a reaction to ageing changes in Bruch’s membrane, which is interposed between the choriocapillaris and the retinal pigment epithelium. The age changes in all three structures have been partly characterised, and as a consequence, multiple putative pathogenic mechanisms have been proposed. Cross-sectional studies of populations with different genetic background and life styles would serve to prove the importance of inheritance and environment. Molecular genetic analysis of blood from affected sibling pairs from these sources may indicate the relevant genes, the prevalence of which may differ in different communities. Enquiries as to life styles may determine important environmental influences. Examination of donor eyes from these communities may reveal distinctive features that may reflect the variation in genetic predisposition and environmental pressures. It is hoped that the findings from such studies will lead to novel and potentially successful management strategies.

Introduction

Research into the age-related changes at the level of Bruch’s membrane is assuming increasing importance. It is reactions to these age-changes that are responsible for visual loss in age related macular degeneration (AMD), which is the leading cause of blindness and partial sight in the elderly populations in Western societies (Leibowitz et al., 1984; Kahn and Moorhead, 1973; Evans, 1995). Moreover, a recent study suggests that AMD is having greater impact amongst the working population (16–64 years) being, for the first time, the leading cause of partially sighted registration in England, and contributes equally with glaucoma and diabetes to blind registration in this age group (Evans and Womald, 1996). AMD is also the only cause for registration that has increased in prevalence over the last decade, with other common causes such as cataracts, diabetes and glaucoma falling. This in part reflects an ageing population and better treatment of other sight threatening conditions, but evidence exists to suggest that the increase may be more than would be expected from these factors alone (Evans, 1995; Evans and Womald, 1996). Finally there is an apparent dramatic rise in the prevalence of AMD in Eastern Asian populations. AMD was considered rare in Japan 20 years ago, but now has become a common cause of poor vision in urban communities (Kubo et al., 1989, Kubo et al., 1990; Maruo et al., 1991). It is evident that AMD is a major health problem of increasing proportions, and to date there is no effective treatment that has made a major impact on the rates of blindness caused by this disorder (Moorfields Macular Study Group, 1982; Chisholm, 1983; Macular photocoagulation study group, 1991, Macular photocoagulation study group, 1993). Age-related changes in Bruch’s membrane have been studied in order to ascertain those factors that determine progression to AMD in some individuals.

The age changes in Bruch’s membrane are due to accumulation of debris derived from the retinal pigment epithelium (RPE) throughout life due to incomplete clearance by the choriocapillaris. In this article we consider the causes and consequences of this accumulation.