Basement membranes and artificial substrates in cell transplantationchange influenced by both genetic predisposition and environmental factors and focused at the level of Bruch's membrane. A number of age-related changes occur at the level of Bruch's membrane [26, 32]. Morphological and biochemical studies have demonstrated that the changes that occur to Bruch's membrane are typified by increased thickness and the progressive accumulation of deposits (such as drusen-see later) within the inner layers of the membrane.Bruch's membrane is a basement membrane complex located between the retinal pigment epithelium (RPE) and the choroid. It is a pentalaminar structure with a central elastin layer bordered on either side by a collagenous zone. There is the basal lamina of the RPE at the innermost collagenous layer of Bruch's membrane and a second basal lamina, produced by the endothelial cells of the choriocapillaris, that is juxtaposed to the outer collagenous layer. Although much more remains to be learned, the basic ultrastructural organization and biochemical composition of Bruch's membrane are similar to basement membrane complexes in other tissues, such as the choroid plexus, kidney glomerulus, and airway alveoli, where an epithelial-endothelial juxtaposition occurs. All ionic exchange and metabolic traffic from the neural retina and RPE to the choroidal capillaries, and vice versa, must traverse Bruch's membrane, thus leaving the neural retina vulnerable to any disruptions of those processes [3]. It is well documented that Bruch's membrane undergoes a number of changes throughout life, including increased thickening, protein cross-linking and reduced permeability to nutrients as well as increased amounts of lipid deposition and the accumulation of basal laminar deposits and drusen (for more detailed reviews see [13, 22,86].Drusen are insoluble deposits that accumulate at the interface between Bruch's membrane and the RPE. Clinically, drusen are divided into two main morphologic phenotypes-hard and soft. Hard drusen are hemispherical structures with well-defined edges, whereas soft This article will concentrate largely on the current developments in the area of cell transplantations presented at the 1st Workshop for Cell Transplantation in Age-related Macular Degeneration. In particular, this brief review will address our current understanding of the role of cell-matrix interactions by covering the pathobiology of normal ageing Bruch's membrane; some of the problems faced at the time of surgery from a basement membrane prospective; the dedifferentiation and differentiation of RPE cells; and how the use of artificial substrates may address several of these issues. We will concentrate on problems related to age-related macular degeneration (AMD), the leading cause of irreversible blindness in Europe, America and other industrialized nations. AMD is likely to be a family of disorders, rather than a single biologic entity, characterized by the progressive loss of sight in the central portion of the visual field [6, 56...