Age-related changes in retinal pigment epithelium.

The retinal pigment epithelium (RPE) is a monolayer of hexagonal organized cells located between the choriocapillaris and the neurosensory retina. As the RPE is implicated in a range of eye diseases, an understanding of its structure and ability for self renewal is critical for therapeutic strategies. Analysis of human RPE cells at the extreme periphery of the retina reveals a population larger in size than those in the centre, they are highly irregular and form an annulus of 4-5 mm. Although binucleation in humans is rare, 10% of these cells are binucleated. In the central region these large binucleated cells are only found adjacent to drusen, which are age-related lipid-rich deposits. Compared with humans, rat RPE is relatively homogeneous, however, the majority of its cells are binucleated, particularly in the central region. Human and rat RPE also shows different patterns of aging. In humans, the centre of the retina shows a significant reduction in RPE cell density with age, which was not observed in aged rats. The capacity of mature RPE cells to enter the cell cycle was investigated using a proliferative marker in rats. Here a subpopulation of mature peripheral RPE cells had the capacity to enter the cell cycle, and one-third of these cells completed cellular division. As RPE proliferation occur in response to retinal detachment, this was performed on rats and the patterns of gene expression in RPE examined. An increase was observed in nestin, PCNA and Ki67 expression, which was also confirmed at a protein level by immunohistochemistry. These results suggest that RPE cells have the capacity to proliferate and may possibly differentiate if subjected to appropriate stimuli in a normal retina