Cunha_edit_Layout 1 22/01/2010 11:04 Page 105
Posterior Segment Retina
The Blood–Retinal Barrier in Retinal Disease
José Cunha-Vaz
President, Association for Innovation and Biomedical Research on Light and Image
Abstract
The blood–ocular barrier system is formed by two main barriers: the blood–aqueous barrier and the blood–retinal barrier (BRB). The BRB
is particularly tight and restrictive and is a physiological barrier that regulates ion, protein and water flux into and out of the retina. The
BRB consists of inner and outer components, the inner BRB being formed of tight junctions between retinal capillary endothelial cells and
the outer BRB of tight junctions between retinal pigment epithelial cells. The BRB is essential to maintaining the eye as a privileged site
and is essential for normal visual function. Alterations of the BRB play a crucial role in the development of retinal diseases. The two most
frequent and relevant retinal diseases, diabetic retinopathy and age-related macular degeneration (AMD), are directly associated with
alterations of the BRB. Diabetic retinopathy is initiated by an alteration of the inner BRB and neovascular AMD is a result of an alteration
of the outer BRB. Treatment of retinal diseases must also deal with the BRB either by using its specific transport mechanisms or by
circumventing it through intravitreal injections.
Keywords
Blood–retinal barrier, blood–ocular barriers, retinal vessels, retinal vascular endothelium, retinal pigment epithelium, blood–aqueous barrier,
macular oedema, vitreous fluorometry, retinal leakage analyser, retinal tight junctions, diabetic retinopathy, retinal drug delivery
Disclosure: The author has no conflicts of interest to declare.
Received: 29 July 2009 Accepted: 27 October 2009
Correspondence: José Cunha-Vaz, AIBILI, Azinhaga Santa Comba, Celas, 3000-548 Coimbra, Portugal. E: cunhavaz@aibili.pt
The entire eye must function as the organ for vision and is Blood–Retinal Barrier
organised with two major goals: normal function of the visual cell The BRB consists of inner and outer components (inner BRB [iBRB]
and the need to maintain ideal optical conditions for the light to and outer BRB [oBRB]) and plays a fundamental role in the
access the visual cells, located in the back of the eye. The microenvironment of the retina and retinal neurons. It regulates fluids
blood–ocular barriers play a fundamental role in the preservation and molecular movement between the ocular vascular beds and
and maintenance of the appropriate environment for optimal visual retinal tissues and prevents leakage into the retina of macromolecules
cell function.
1
The blood–ocular barriers include two main barrier and other potentially harmful agents (see Figures 1 and 2).
systems – the blood–aqueous barrier and the blood–retinal barrier
(BRB) – which are fundamental to keeping the eye as a privileged The iBRB is established by the tight junctions (zonulae occludentes)
site in the body by regulating the contents of its inner fluids and between neighbouring retinal endothelial cells.
4,5
The retinal endothelial
preserving the internal ocular tissues from the variations that occur layer functions as an ‘epithelium’ and in this way is directly associated
constantly in the whole circulation. The BRB, similar to the with its differentiation and with the polarisation of BRB function. This
blood–brain barrier (BBB), is particularly tight and restrictive and is continuous endothelial cell layer, which forms the main strutucture of
a physiological barrier that regulates ion, protein and water flux the iBRB, rests on a basal lamina that is covered by the processes of
into and out of the retina.
2
astrocytes and Müller cells. Pericytes are also present, encased in the
basal lamina, in close contact with the endothelial cells, but they do not
The blood–ocular barriers must not only provide a suitable, highly form a continuous layer and therefore do not contribute to the
regulated chemical environment for the avascular transparent tissues diffusional barrier. Astrocytes, Müller cells and pericytes are considered
of the eye, but also serve as a drainage route for the waste products to influence the activity of retinal endothelial cells and of the iBRB by
of the metabolic activity of the ocular tissues. It is also important to transmitting regulatory signals to endothelial cells indicating changes
realise that once inside these barriers there are no major diffusional in the microenvironment of the retinal neuronal circuitry.
barriers between the extracellular fluid of the retina and adjacent
vitreous humour; nor does the vitreous body itself significantly hinder The oBRB is established by the tight junctions (zonulae occludentes)
the diffusional exchanges between the posterior chamber and the between neighbouring retinal pigment epithelial (RPE) cells.
6,7
The RPE
retinal extracellular fluid. This means that the functions of both is composed of a single layer of retinal pigment epithelial cells that
barriers – the blood–aqueous barrier and the BRB – influence each are joined laterally towards their apices by tight junctions between
other and must work in equilibrium.
3
adjacent lateral cell walls. The RPE, resting on the underlying Bruch’s
© TOUCH BRIEFINGS 2009 105
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116