Histopathology

Core Messages

›The retinal pigment epithelium (RPE) including its diverse functions and interplay with photoreceptors and choriocapillaris plays a central role in the pathogenesis of exudative and atrophic AMD.

›Especially age-related changes and deposits in the RPE and Bruch’s membrane are responsible for the morphological degenerations seen in AMD etiopathology.

›The characteristics of these age-related changes determine whether late forms of AMD - distinguished by RPE cell death or induction of choroidal neovascularization (CNV) - will manifest.

A.Lommatzsch (*) D. Pauleikhoff

Department of Ophthalmology, St. Franziskus Hospital, Münster, Germany

e-mail: albrecht.lommatzsch@web.de; dapauleikhoff@muenster.de

S. Wasmuth

Ophtha-Lab, Department of Ophthalmology, St. Franziskus Hospital,

Münster, Germany

e-mail: susanne.wasmuth@makula-centrum-muenster.de

F.G. Holz

Department of Ophthalmology, University of Bonn, Bonn, Germany

e-mail: frank.holz@ukb.uni-bonn.de

A.C. Bird

Department of Ophthalmology, Moorfields Eye Hospital, London, UK

e-mail: alan.bird@ucl.ac.uk

5.1Retinal Pigment Epithelium

5.1.1Structure and Function of the Retinal Pigment Epithelium

The basal membrane of the monolayered retinal pigment epithelium (RPE) is limited by Bruch’s membrane and the adjacent layer of the choroid, which is rich in capillaries. At the apical side the microvilli of the RPE are in close contact to the photoreceptor outer segments. There is a complicated metabolic exchange between the retina and choroid with the RPE as a key player. In the recycling of pigment during the visual cycle, the shed discs of the photoreceptor outer segments are phagocytozed by the RPE cells and final metabolic products are disposed in the direction of the choroid. The RPE also regulates the nutritional supply and the extracellular ionic microenvironment of the photoreceptors. The resulting osmotic depression contributes to retinal adhesion of the RPE and can thus prevent retinal detachment. The production and directed secretion of different growth factors contribute to the maintenance of the functional unit composed of the photoreceptors, RPE cell layer and choroid.

Functions of the monolayered RPE (see also Fig. 5.1):

•Absorption of light

•Transport (nutrients from blood to photoreceptors and removal of final metabolic products from the subretinal space to the choroid)

•Compensation of quick, light-dependent changes of the ionic concentration in the subretinal space

•Transport of chloride: basic principle of the electrooculogram

•Retinal cycle

•Phagocytosis

Choroid

•Immune regulation

•Secretion

Many kinds of blindess are due to altered or lost

RPE functions or cellular loss of RPE cells. The healthy RPE is very flexible in reacting to retinal changes and those in the blood flow. Therefore, signs of alterations and diseases are often visible early in the RPE. However, the RPE cells may be a good therapeutic target for obtaining a correcting influence on degenerative diseases and those of the photoreceptors [1, 2].

RPE

Photoreceptor cells

1.metabolism of vitamin A

2.optic function

3.bilateral transport function

4.generation of potential (detectable in electro oculogram)

5.phagocytosis + degradation

(most notably of photoreceptor outer segments)

6.regulatory functions (such as release of growth factors)

7.immunological functions

97 years

43 years

9 years

5.1.2Age-Related Changes of the RPE

A critical function of the RPE is phagocytosis and degradation of the shed photoreceptor outer segments. The daily phagocytosis rate is about 7% of the RPE cell volume. Because of this extremely high rate of phagocytosis, an increasing accumulation of lipofuscin in the

Fig. 5.2 Increasing accumulation of autofluorescent material (green) and lipofuscin (yellow) with increasing age

RPE cells during life is found (Fig. 5.2). Non-degradable constituents of the photoreceptor outer segments are an important source of lipofuscin. During the first decade of life about 2% of the RPE cytoplasm is occupied by lipofuscin. This increases to approximately 20% at the