Retinal Pigment Epithelium
• Develops from the outer layer of the optic cup.
• Consists of a monolayer of hexagonal cells.
• Extends anteriorly from the optic nerve head to the ora serrata.
• Merges with the pigmented epithelium of the ciliary body.
• Structure is deceptively simple considering its many functions:
◦ Vitamin A metabolism
◦ Formation and maintenance of the outer blood–ocular barrier
◦ Phagocytosis of the photoreceptor outer segments
◦ Absorption of light (reduction of scatter)
◦ Formation of the basal lamina of Bruch membrane
◦ Production of the mucopolysaccharide matrix surrounding the outer
segments
◦ Maintenance of retinal adhesion
◦ Active transport of materials into and out of the RPE
◦ Management of reactive oxygen species
• Polarized cells (like other epithelial and endothelial cells).
• Basal aspect:
◦ Intricately folded.
◦ Provides large surface of attachment to the thin basal lamina (inner layer of
Bruch membrane).
• Apices:
◦ Multiple villous processes.
◦ Envelop and engage with the photoreceptor outer segments.
• No physical connection between RPE and photoreceptors despite numerous
interactions.
◦ Clinical Relevance: Separation of RPE from neurosensory retina is called
retinal detachment.
• Contiguous RPE cells firmly attached by lateral junctional complexes:
◦ Zonulae occludentes and zonulae adherentes:
▪ Provide structural stability.
▪ Play important role in maintaining the outer blood–ocular barrier.
◦ Zonula occludens:
▪ Junction where adjacent plasma membranes are fused.
▪ Forms a circular band or belt around adjacent cells.
◦ Zonulae adherentes:
▪ Small intercellular space present between them.
• Junctions establish polarity of molecules within apical and basal cell membranes.
• Limit paracellular transport.
• Allow RPE to regulate transfer of nutrients and macromolecules between
choriocapillaris and outer retina.
• Supports unidirectional flow of water (aqueous humor) across the retina and into
the choroid.
Clinical Relevance (HIGH-YIELD): * The flow of aqueous humor across the retina and
into the choroid helps maintain retinal adhesion. * The polarity of water transport is
maintained by the tight junctions of the outer blood–retinal barrier and both active and
passive processes that direct the flow. * In cases of retinal tears (with or without retinal
detachment), there is increased flow of aqueous humor across the retinal break. * This
can lead to reduced IOP in the affected eye.
• RPE Cell Characteristics:
◦ Diameter:
▪ Macula: 10–14 μm
▪ Periphery: 60 μm
◦ Foveal vs. Peripheral RPE Cells: Foveal cells are taller, thinner, contain more
melanosomes, and have larger melanosomes compared to peripheral RPE
cells.
• These characteristics account in part for the decreased transmission of choroidal
fluorescence observed during fundus fluorescein angiography in the macula.
• The eye of a fetus or infant contains between 4 and 6 million RPE cells.
• Although the surface area of the eye increases appreciably with age, the increase in
the number of RPE cells is relatively small.
• No mitotic figures are apparent within the RPE of the healthy adult eye.
• The cytoplasm of the RPE cells contains multiple round and ovoid pigment
granules (melanosomes).
• These organelles develop in situ during formation of the optic cup and first appear
as nonmelanized premelanosomes.
• Their development contrasts sharply with that of the pigment granules in uveal
melanocytes, which are derived from the neural crest and later migrate into the
uvea.
Clinical Relevance (HIGH-YIELD): * Loss of melanin production within the RPE and
melanocytes within the choroid and iris occurs in patients with ocular and
oculocutaneous albinism. * Absence of melanin during development can lead to
improper neuronal migration and development. * Lack of pigmentation within the
posterior segment can impair uptake during laser photocoagulation.
• RPE cells also possess phagocytic function; they continually ingest the disc
membranes shed by the outer segments of photoreceptor cells, enclosing them
within phagosomes.
• Several stages of disintegration are evident at any given time.
• In some species, shedding and degradation of the membranes of rod and cone
outer segments follow a diurnal rhythm synchronized with daily fluctuations of
environmental light.
• Lipofuscin granules within the RPE probably arise from the discs of photoreceptor
outer segments and represent residual bodies from phagosomal activity.
• This so-called “wear-and-tear” pigment is less electron-dense than are the
melanosomes, and its concentration increases gradually with age.
• Clinically, these lipofuscin granules are responsible for the signal observed with
fundus autofluorescence imaging.
Clinical Relevance (HIGH-YIELD): * Throughout life, incompletely digested residual
bodies, lipofuscin, phagosomes, and other material are excreted beneath the basal
lamina of the RPE. * These contribute to the formation of drusen, which are
accumulations of this extracellular material. * Drusen can vary in size and are commonly
classified by their ophthalmoscopic appearance as hard or soft. * They are typically
located between the basement membrane of RPE cells and the inner collagenous zone
of Bruch membrane. * Large soft drusen are associated with intermediate-stage age-
related macular degeneration.
• The cytoplasm of the RPE cell contains numerous mitochondria (involved in
aerobic metabolism), rough-surfaced endoplasmic reticulum, a Golgi apparatus,
and a large round nucleus.
• The RPE utilizes all methods of glucose metabolism to generate energy and
nicotinamide adenine dinucleotide phosphate (NADPH).
• The latter assists the RPE in managing reactive oxygen species and regulating
oxidative stress.
Bruch Membrane
• Bruch membrane is a PAS-positive lamina resulting from the fusion of the basal
laminae of the RPE and the choriocapillaris of the choroid.
• It extends from the margin of the optic nerve head to the ora serrata.
• Ultrastructurally, Bruch membrane consists of 5 elements:
◦ basal lamina of the RPE
◦ inner collagenous zone
◦ relatively thick, porous band of elastic fibers
◦ outer collagenous zone
◦ basal lamina of the choriocapillaris
• It is highly permeable to small molecules such as fluorescein.
• Defects in the membrane may develop in myopia, pseudoxanthoma elasticum,
trauma, or inflammatory conditions.
◦ Clinical Relevance: These defects may lead to the development of choroidal
neovascularization.
• With age, debris accumulates in and thickens Bruch membrane.
Ora Serrata
• The ora serrata separates the retina from the pars plana.
• Ora Serrata Dimensions:
◦ Distance from Schwalbe line:
▪ Nasal: 5.75 mm
▪ Temporal: 6.50 mm
▪ Clinical Relevance: Distance is greater in myopia, shorter in hyperopia.
◦ Eye Measurements:
▪ At Ora Serrata: Diameter 20 mm, Circumference 63 mm
▪ At Equator: Diameter 24 mm, Circumference 75 mm
• Externally, the ora serrata lies beneath the spiral of Tillaux.
• Topographically, the margin of the ora serrata is relatively smooth temporally and
serrated nasally.
• Retinal blood vessels end in loops before reaching the ora serrata.
• The ora serrata is in a watershed area between the anterior and posterior vascular
systems.
◦ Clinical Relevance: This location may in part explain why peripheral retinal
degeneration is relatively common.
• The peripheral retina in the region of the ora serrata is markedly attenuated.
• The photoreceptors are malformed, and the overlying retina frequently appears
cystic (Blessig-Iwanoff cysts).
Vitreous
• Vitreous Characteristics:
◦ Volume: Occupies four-fifths (80%) of the globe volume; approximately 4.0
mL total volume.
◦ Composition: 99% water.
◦ Viscosity: Approximately twice that of water, due to hyaluronic acid.
• The transparent vitreous humor is important to the metabolism of the intraocular
tissues because it provides a route for metabolites used by the lens, ciliary body,
and retina.
• At the ultrastructural level, fine collagen fibrils (chiefly type II) and cells have been
identified in the vitreous.
• The origin and function of these cells, termed hyalocytes, are unknown, but they
probably represent modified histiocytes, glial cells, or fibroblasts.
• The fibrils at the vitreous base merge with the basal lamina of the nonpigmented
epithelium of the pars plana and, posteriorly, with the ILM of the retina, the
vitreoretinal interface.
• The vitreous adheres to the retina peripherally at the vitreous base.
◦ Vitreous Base Extent: Straddles the ora serrata, extending from 2.0 mm
anterior to the ora serrata to approximately 4.0 mm posterior to it.
• Additional attachments exist at the optic nerve head margin, at the perimacular
region surrounding the fovea, along the retinal vessels, and at the periphery of the
posterior lens capsule (hyaloideocapsular ligament; also known as ligament of
Wieger).
• A prominent area of liquefaction of the premacular vitreous gel is called the
premacular bursa, or precortical vitreous pocket.
