Ординатура / Офтальмология / Английские материалы / Retinal and Choroidal Angiogenesis_Penn_2008

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Chapter 24

CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION—FROM MICE TO MAN

Lennart Berglin

St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden

1.BACKGROUND

Exudative macular degeneration is the major sight-threatening disease in people over 60 years of age in the western world. Until now, most therapies have only had limited effect in preserving visual function. Lately, molecular remedies, mostly based on research in mice, have been introduced that give some hope of improving the visual outcome in these severe cases. There are several indications of an inflammatory reaction correlated to choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Titers of Chlamydia pneumoniae have been elevated in some cases.1,2 Drusen, deposits of cellular debris associated with AMD, seem to attract the immune system, e.g., complement factors,3 human leukocyte antigen, and dendritic antigen-presenting cells.4 Macrophages can initially clear the

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deposits, but with increasing age, the immune system is depressed, and debris accumulates. There are several other, non-AMD-associated, inflammatory etiologies to CNV: presumed ocular histoplasmosis (POHS), acute multifocal placoid pigment epitheliopathy (AMPPE), toxoplasmosis, and birdshot retinopathy. CNV is also a well-known complication of other diseases with breaks in the Bruch’s membrane, RPE and choroids, e.g., trauma, high myopia, and angioid streaks (Pseudoxanthoma elasticum).5

Vascular endothelial growth factor (VEGF), the choroidal survival factor, is normally secreted to the basolateral side of the retinal pigment epithelium (RPE) by a factor of 7:1 compared to the apical side (Figure 1),6,7 but with increasing age and lipification, the Bruch’s membrane is less penetrable to VEGF and other molecules, e.g., oxygen. The aging process could lead to choroidal atrophy and concomitant relative hypoxia in the outer retina, stimulating VEGF production.7 Increased levels of VEGF could then reduce the tight junction function of the RPE, causing a breakdown of the bloodretina barrier, which is vital for upholding the integrity of the interface, including molecular separation. This could create conditions amenable to vascular ingrowth through a compromised Bruch’s membrane into the subretinal space.

Figure 24-1. Blood-retina barrier. (Adapted from Schlingemann R.O.: Role of growth factors and wound healing response in age-related macular degeneration. Graefes Arch. Clin. Exp. Ophthalmol. 2003; 242(1):91-101.)