Development, repair and regeneration of the retinal pigment epithelium

Abstract

An overview is presented of the retinal pigment epithelium (RPE) cell in repair and regeneration. Changes in the RPE associated with repair activities have been described as metaplasia. However, evidence is presented to show that RPE cells do not become either fibroblasts or macrophages but merely adopt the appearance of these cell types in pathological conditions. The phenotypic alterations seem to be substrate-related. The fibroblast form predominates on two-dimensional substrates rich in fibronectin and in three-dimensional collagen matrices. The macrophage form seems to be associated with insubstantial or inadequate substrates such as the vitreous, photoreceptor debris and some cell surfaces. In altered circumstances the dedifferentiated RPE can rapidly revert to an epithelioid form. However, the regeneration of an effective RPE mosaic is more difficult and dependent on many factors including the size of the initial lesion, the condition of the basement area, the status of the neuroretina and the existing pathology in the eye. The importance for the regeneration of a normal functioning RPE of the cells being out of the cell cycle, establishing effective junctioning, reorganising their cytoskeleton and having the required adhesive balance with the basement membrane is emphasised.

Long‐term outcome of RPE allografts to the subretinal space of rabbits

“…It cannot be ruled out that the host RPE cells, also, can act as macrophages (Grierson et al 1994). Macrophage responses are known to be common in retinal diseases (Nicolai & Eckardt 1993).…”

“…ACAID is an acquired process that is associated with the active suppression or down-regulation of a systemic delayed-type of hypersensitivity (Dafgård Grierson et al 1994;Streilein et al 1997). These events are mediated by eye-derived signals that escape to the peripheral blood with bloodborne leukocytes that express a mature macrophage/monocyte marker (Rezai et al 1997;Wilbanks et al 1991).…”

Retinal degeneration triggered by inactivation of PTEN in the retinal pigment epithelium

“…The RPE supports visual processes through the removal of spontaneously generated toxic metabolites and the phagocytic renewal of photoreceptor outer segments (Bok 1993;Grierson et al 1994;Marmorstein et al 1998;Zarbin 1998;Adler et al 1999;Schraermeyer and Heimann 1999). Given the high level of PTEN in the RPE, we investigated its role in this epithelium by generating mice that lack the phosphatase specifically in RPE cells (Fig.…”

“…Although impairment of RPE structural integrity is known to lead to retinal degenerative diseases such as age-related macular degeneration (AMD) and some forms of retinitis pigmentosa (RP), the molecular mechanisms that regulate RPE structure have remained elusive (Grierson et al 1994;Zarbin 1998;Adler et al 1999;Schraermeyer and Heimann 1999). One of the major causes of AMD is oxidative stress, which is generated both endogenously during the course of phototransduction, and also by a variety of exogenous insults (Cai et al 2000;Bailey et al 2004;Wenzel et al 2005).…”

Cyclosporine treatment of RPE allografts in the rabbit subretinal space

“…The interpretation of the cellular response is complicated by the fact that native RPE cells are able to phagocytize foreign material from disrupting transplanted RPE cells (Grierson et al 1994). Macrophages, also, enter the subretinal space and participate in this process.…”