33
Pathogenic Mechanisms
3
Age-related changes that predispose to age-related macu-
lar degeneration (AMD) occur in the outer retina, more
specifically the region that includes the photoreceptors
(PR), the retinal pigment epithelium (RPE), Bruch’s
membrane and the choriocapillaris.
Retinal anatomy is highly organized and vascular and
avascular compartments are strictly segregated in the
retina
(1)
. The blood-retinal barriers, inner and outer, are
fundamental for the integrity of structure and optimiza-
tion of function in neuro-sensorial retina
(2)
.
The outer blood-retinal barrier is formed, among its
various components, by the RPE tight junctions. The
intercellular cohesiveness of the RPE is not easily dis-
rupted. Tight junctions appear as a necklace of strands
that encircle each cell, binding each cell to its neighbours
in a monolayer that separates the outer layer of the neu-
ral retina from the choriocapillaris
(3)
. Choriocapillaris is
a great vascular network of fenestrated capillaries with
high blood flow, fundamental for the metabolism of
outer retina. This outer blood-retinal barrier retards tran-
sepithelial diffusion through the paracellular spaces
(3)
.
The RPE is a polarized epithelium that consists of a con-
tinuous pavement-like monolayer of cuboidal shaped
cells that in macular area are tall, narrow and highly
uniform in size and shape
(4)
. Interdigitation of the apical
processes of the RPE with the cone and rod outer seg-
ments provides only a tenuous adhesion of the RPE to
the sensory retina
(5)
.
RPE cells have at least ten known functions, but regen-
eration of visual pigments, transport of fluids and ions
between photoreceptors and choriocapillaris, formation
and maintenance of the interphotoreceptor matrix and
Bruch’s membrane and phagocytosis of outer segments
of PR should be emphasized
(6)
.
Bruch’s membrane is a thin, acellular and well-delineated
membrane with five layers. From internal to external,
these layers are: the basement membrane of the RPE, the
inner collagenous zone, the elastic tissue layer, the outer
collagenous zone and the basement membrane of the
choriocapillaris. It is composed of elements from both,
the retina and choroid, but is an integral part of the cho-
roid
(7)
. Its inner surface is smooth, whereas its outer sur-
face is composed of a series of collagenous protrusions
that extend externally to form the pillars separating and
supporting the choriocapillaris
(5)
. Due to its specific lo-
cation and properties, this tissue is thought to be a vital
limiting layer for metabolic transport between the RPE
cells and the choriocapillaris
(8)
.
The choriocapillaris consists of a continuous layer of
fenestrated endothelial cells surrounded by a basement
membrane. In the macula the choriocapillaris is arranged
in a lobular pattern of highly concentrated intercon-
necting capillaries supplied by a central arteriole and
drained by circumferential venules
(5,9)
. The fenestrations,
60-80 nm in diameter, are abundant and seem to play an
important role in permitting the passage of glucose and
vitamin A to the RPE and retina. The choriocapillaris
supplies oxygen and nutrients to Bruch´s membrane and
the outer third of the retina, except in the macula, where
it supplies the entire retina
(7)
. The peculiar structure of
the choroidal vascular tree in the macula provides this
area with the highest rate of blood flow of any tissue in
the body
(5)
.
With aging the lumina of the choriocapillaris and
the choroidal thickness become reduced by half
(10)
.
1. The outer retina
Author:
Ângela Carneiro, MD
Faculty of Medicine of University of Porto, Hospital S. João, Porto, Portugal.
2. Aging changes in outer retina and
early AMD
