The Role Of Eye-Associated Lymphoid Tissue In Corneal Immune Protection

J. Anat. (2005) 206, pp271–285

REVIEW
Blackwell Publishing, Ltd.

The role of eye-associated lymphoid tissue in corneal
immune protection
Erich Knop1 and Nadja Knop2
1
2

Research Laboratory of the Eye Clinic CVK, Charite – University School of Medicine, Berlin, Germany
Department of Cell Biology in Anatomy, Hannover Medical School, Hannover, Germany

Abstract
Because the corneais optimized for refraction, it relies on supporting tissues for moistening and nutrition and in
particular for immune protection. Its main support tissue is the conjunctiva, in addition to the lacrimal gland, the
latter which provides soluble mediators via the tear film. The cornea and conjunctiva constitute a moist mucosal
surface and there is increasing evidence that apart from innate defencemechanisms, also lymphoid cells contribute
to the normal homeostasis of the corneal surface. A Medline-based literature search was performed in order to
review the existing literature on the existence, composition and functions of mucosa-associated lymphoid tissue
(MALT) at the ocular surface for corneal protection. The existence of lymphoid cells at the ocular surface and
appendage has beenknown for many years, but for a long time they were believed erroneously to be inflammatory
cells. More recent research has shown that in addition to the known presence of lymphoid cells in the lacrimal
gland, they also form MALT in the conjunctiva as conjunctiva-associated lymphoid tissue (CALT) and in the lacrimal
drainage system as lacrimal drainage-associated lymphoid tissue (LDALT).Together this constitutes an eyeassociated lymphoid tissue (EALT), which is a new component of the mucosal immune system of the body. When
the topographical distribution of CALT is projected onto the ocular surface, it overlies the cornea during eye closure
and is hence in a suitable position to assist the corneal immune protection during blinking and overnight. It can
detect corneal antigens andprime respective effector cells, or distribute protective factors as secretory IgA.
Key words conjunctiva; cornea; defence; eye-associated lymphoid tissue (EALT); mucosal immunity.

Introduction
The cornea is the most important structure of the
ocular surface for the maintenance of visual function.
Its anatomy is optimized for clarity in order to perform
maximal light transmission, and forconsistency of
dimensions and radius in order to perform a stable
refraction. The cornea consists mainly (apart from the
epithelia at both sides) of a relatively stiff piece of dense
connective tissue (stroma) built up by tightly arranged

Correspondence
Dr Erich Knop, Research Laboratory of the Eye Clinic CVK, Charite – University School of Medicine Berlin, Ziegelstr. 5–9, 10117 Berlin,Germany.
T: +49 030450 554027; E: erich.knop@charite.de
Accepted for publication 10 January 2005
© Anatomical Society of Great Britain and Ireland 2005

lamellae of collagen bundles (Bron et al. 1997). The
cornea contains relatively few cells in the stroma, and
most of these are so-called keratocytes (fibrocytes);
there are no lymphoid cells or other apparent protective elements, apart fromsome dendritic cells and their
precursors (Hamrah et al. 2003). For a number of functions such as moistening and nutrition, and also for
the purpose of defence, the cornea therefore depends
largely on its major support tissue – the conjunctiva – in
addition to soluble factors that are provided via the
tear film by the lacrimal gland. It is increasingly recognized that the conjunctiva is alsoinvolved in the local
production of factors such as secretory IgA, the production of which was formerly believed to be exclusively
located in the lacrimal gland (Knop et al. 2003).
Unlike the cornea, the conjunctiva is composed of a
loose connective tissue layer (lamina propria) beneath

272 The role of EALT in corneal immune protection, E. Knop and N. Knop

The ocular surface is a part of...