The visual unit for the detection and transmission of information comprises four compartments. The photoreceptor cell is the detector of light and communicates this information to other cells in the retina. The RPE cell provides metabolic support to the photoreceptor cell by delivering all its nutrients and removing waste products. There are tight junctions between RPE cells so that all nutrients and waste products exchanged between the photoreceptor cell and the blood supply must traverse this RPE cell. The third compartment is Bruch's membrane and this is essentially a filter that allows selective entry of blood components to be presented to the RPE for delivery to photoreceptor cells. It also serves as a barrier to the growth of blood vessels which if allowed to penetrate Bruch's would lead to the death of the photoreceptors. Finally, the fourth compartment is the choriocapillary blood supply that brings nutrients and removes waste products. The capillaries are fenestrated and therefore allow the release of most blood constituents to be presented to Bruch's membrane. The normal operation of all four compartments is essential for maintaining the structure and function of the visual process for the detection of light.

Communication with other cell types in the retina occurs at the synaptic pedicle of the photoreceptor cell. In the dark, neurotransmitters (aspartate and glutamate) are released continuously and this tells other cells in the retina that the photoreceptor is in the dark. A flash of light causes a reduction in the amount of transmitter released. The higher the intensity of light, the greater the decrease in the release of transmitters. Thus, the photoreceptor informs other cells in the retina about the presence and intensity of the light signal.

The inner segment is the power house of the cell containing regions packed with mitochondria and these produce ATP for synthetic purposes. This region of the cell is also the factory of the cell. It continuously synthesises disk membranes that are added at the junction of the inner and outer segment of the cell. As these discs are added, others at the tip of the outer segment are phagocytosed by the RPE. This synthetic capacity is so great that the whole outer segment is replaced within about 10 days, and this process is active throughout life.

The outer segment is the light detector in the photoreceptor cell. Each outer segment contains about 1000 membrane discs and embedded within the membranes is the photopigment protein rhodopsin. The detector is very sensitive such that the activation of a single rhodopsin molecule (with one photon) anywhere in the outer segment can elicit a physiological response.

The RPE performs many functions that are essential for the survival of photoreceptor cells. Firstly, the presence of tight junctions between RPE cells provides a blood-retinal barrier allowing the ionic composition around photoreceptors to be tightly regulated. Secondly, the RPE cell has protein carriers on both apical and basal surfaces that allow the delivery of essential nutrients from the blood to photoreceptor cells. Conversely, it facilitates the removal of waste products into the circulation. Thirdly, the RPE pumps fluids out of the retina and onto Bruch's for clearance into the blood. Fourthly, the RPE phagocytoses or "bites off" packets of outer segment discs, on a daily basis, and degrades these, sending the components back to the photoreceptor cell for further synthesis. The removal of discs by the RPE and synthesis in the photoreceptor is balanced so that the length of the outer segment remains constant. This process is very important in maintaining the photoreceptor cell and is discussed in more detail below.

As we have stated previously, the efficient transport of fluids and nutrients across Bruch's is essential for the survival of both the RPE and photoreceptor cells.

Fluid arising in the retinal layers is actively pumped out by the RPE onto Bruch's membrane. From here, the fluid is removed passively across Bruch's membrane [1] into the choroidal circulation.

Nutrients crossing Bruch's membrane can be divided into three groups. Small molecules such as glucose, amino acids, etc., exist in a free form and cross Bruch's by passive diffusion and are picked up by active/passive carriers on the basal surface of the RPE for transport to the photoreceptors. Other nutritional molecules that are normally hydrophobic or toxic in free form enter Bruch's complexed to some protein carrier. The carrier crosses Bruch's and on interaction with the RPE releases its cargo for uptake [2]. Very large molecular complexes such as the lipoproteins may partially enter Bruch's and release their cargo for further diffusion across Bruch's membrane [3]. Waste products on the other hand move in the opposite direction to be removed by the choroidal circulation.

Ageing of Bruch's and the RPE is expected to alter these transport properties. Several workers have examined the effect of ageing on the transport of fluids and nutrients and their results are briefly discussed below.

Normal turnover of Bruch's membrane

In Bruch's, a unique mechanism operates to maintain the structural and functional characteristics of the membrane. Components are continuously being broken down and replaced so as to rejuvenate the membrane. This process should therefore serve to remove the waste aggregates that become trapped in the membrane.

The degradation process is mediated by a family of calcium-containing, zinc-dependent proteolytic enzymes known as the matrix metalloproteinases (MMPs). These enzymes, upon activation, can breakdown virtually all components within the matrix of Bruch's membrane.

In young Bruch's membrane, the process of degradation is clearly evident since we observe the presence of activated MMPs. As we get older, this ability to degrade the matrix becomes less effective leading to the accumulation of damaged components and debris. For example, in the elderly, nearly 50% of collagen of Bruch's exists in a damaged state. There are many reasons why the degradation may be ineffective. The debris may be so damaged that the MMPs simply cannot break it down. Increasing amounts of debris may block access of the enzymes to their substrates. Furthermore, we know that some components actually inhibit the MMP enzymes.

The degradation ability slows with age but synthesis of new components continues and therefore the thickness of Bruch's increases with age. Bruch's is about 2-3 times thicker in the elderly compared to that in the young. The increased thickness, together with the deposition of debris is expected to compromise the transport pathways through Bruch's membrane