Abstract
The choroid is the vascular bed of the eye. It is separated from the retina by a fibrous tissue structure, called Bruch’s membrane (BM). Adjoining to BM is the choriocapillaris, a layer of large caliber capillaries with fenestrated endothelium that nourishes the outer retina. Besides, there are small and medium-sized vessels that are present in (inner) Sattler’s layer and large vessels (veins and arteries) present in Haller’s layer. The stroma is rich in connective tissue elements, melanocytes, and nerves supplying to the vessels. In aging and age-related macular degeneration, debris accumulates in BM; this hampers nutrient transfer to outer retina from the choriocapillaris. Also, the retinal pigment epithelium-secreted molecules that fail to reach the choriocapillaris, leading to a decreased capillary density in the submacular zone. In certain diseases, large vessels are also affected. Since photoreceptors die, ultimately, due to major alterations at the BM–choriocapillaris interface, it is imperative to know about the mechanisms of normal maintenance of the choroidal vessels.
Keywords
Choroid, Bruch’s membrane, Choriocapillaris, Stroma, Choroidal vessels
Introduction
The choroid is sandwiched between the sclera and Bruch’s membrane (BM) of the eye. It is the predominant vascular bed of the eye and contains diverse cell types forming the stroma. It performs a number of anatomical, physiological, photoprotective, and immunological functions. Many of these functions are understood from studies employing electron microscopy. This chapter illustrates the structural features of the choroidal elements and how they are related to its functions. An attempt is made to describe how they alter with aging and diseases, for example, age-related macular degeneration (AMD).
Keywords
Choroid, Bruch’s membrane, Choriocapillaris, Stroma, Choroidal vessels
Introduction
The choroid is sandwiched between the sclera and Bruch’s membrane (BM) of the eye. It is the predominant vascular bed of the eye and contains diverse cell types forming the stroma. It performs a number of anatomical, physiological, photoprotective, and immunological functions. Many of these functions are understood from studies employing electron microscopy. This chapter illustrates the structural features of the choroidal elements and how they are related to its functions. An attempt is made to describe how they alter with aging and diseases, for example, age-related macular degeneration (AMD).
Contents of the Choroid
The choroid shows five distinct regions: (1) BM, (2) the choroiocapillaris, (3) Sattler’s layer (with small and medium-sized vessels), (4) Haller’s layer (with large vessels), and (5) the suprachoroid. It is separated from the retina by a composite structure, called BM, which behaves like a filtration barrier to it. Adjoining to BM, there is a layer of capillaries, called choriocapillaris ( Fig. 2.1A and B ), which supplies oxygen and nutrients to the outer retina. The remainder of the choroid, the stroma, is populated by melanocytes, connective tissue elements (fibroblasts, mast cells, elastic, and collagen fibrils), blood vessels ( Fig. 2.1A, C, and D ), macrophages, dendritic cells, lymphocytes, nonvascular smooth muscle cells (NVSMC), intrinsic neurons, and nerve fibers associated with vessels.
Choroidal Thickness
The choroidal thickness varies over its entire extent. It is thicker in the subfoveal zone than elsewhere; the thickness, measured with enhanced depth imaging optical coherence tomography, is reportedly between 250 μm and 330 μm, which is thicker than temporal or nasal counterparts. Choroidal thinning occurs in aging macula, high axial length, and in certain diseases, for example, glaucoma, pseudoxanthoma elasticum, and in birdshot chorioretinopathy. Its thickness remains unaltered in advanced stages of AMD.
Fine Structure of BM
BM is pentalaminate ( Fig. 2.2A ) and consists of (1) the basal lamina of the retinal pigment epithelium (RPE), (2) inner collagenous layer, (3) elastic layer, (4) outer collagenous layer, and (5) the basal lamina of the choriocapillaris endothelium. It measures 2.5–3.0 µm in the submacular zone and 1.5–2.0 µm in the periphery.
Changes in BM in Aging and Diseases
BM alters with age and in AMD. It thickens in submacular region up to 4.7 μm in 10th decade of life due to accumulation of debris ( Fig. 2.2B–F ), such as long-spacing collagens, fibrous-banded materials, vesicles, lipids, and lipoprotein-like particles. The elastic lamina thickens and become irregular in aging ( Fig. 2.2D and E ). In AMD, BM may contain iron in its elastic layer and undergoes calcification and fragmentation, in eyes with exudative AMD. Also, there is formation of drusen, and basal linear deposits (BLinD) between the RPE basal lamina and inner collagenous layer of BM ( Fig. 2.2F ), and basal laminar deposits (BLamD) beneath the RPE basal lamina. Drusen in eyes with AMD may contain carbohydrates, proteins, and abundant neutral lipids in age-related maculopathy. In eyes with AMD, there is an exclusive presence of soft, large, and diffuse drusen and abundant BLamD, whereas large drusen and BLinD are specific for early age-related maculopathy. RPE atrophy leads to formation of large, soft drusen (diameter >30 µm), a risk factor for the onset of neovascular AMD when choroidal vessels grow into RPE. BM deposit results from partial removal of RPE debris, which leads to a decrease of BM permeability. This hampers the diffusion of macromolecules from choriocapillaris to outer retina via BM, resulting in gradual loss of photoreceptors. Due to the decreased BM permeability, RPE-released vascular endothelial growth factor (VEGF) cannot diffuse to the choriocapillaris, leading to its atrophy.
Choriocapillaris
The choriocapillaris is a network of wide-caliber capillaries (diameter: 10–40 μm; Fig. 2.3A ). It is about 10–12 μm thick at the macula and 6–7 μm in the periphery. The macular region contains the highest density of capillaries. Their lumen is lined by endothelial cells whose cytoplasm is attenuated and fenestrated at the retinal aspect ( Fig. 2.3B–D ) and contain Weibel–Palade bodies, pinocytotic vesicles ( Fig. 2.3E ), and intermediate filaments ( Fig. 2.3E–G ). The cells are connected by tight junctions ( Fig. 2.3E ). Outer to the endothelium, there is a layer of pericytes ( Fig. 2.3F and G ) surrounded by the same basal lamina that lines the endothelium ( Fig. 2.3B–G ). Peg and socket joints are present between endothelial cells and pericytes. The pericytes contain large nuclei and intermediate filaments and help in thermoregulation. It is unknown if they are contractile. Cytoplasmic processes from the endothelium often protrude into BM ( Fig. 2.3D ). These may play a role in the maintenance of patency of the vessels and clearance of BM debris.
Changes in Choriocapillaris in Aging and Diseases
The choriocapillaris alters considerably in early AMD, Sorsby’s fundus dystrophy, glaucoma, and diabetes ; there may be loss of endothelial cells and decreased number of endothelial fenestrations (AMD). RPE atrophy is associated with choriocapillaris loss in peripapillary area in aging eyes. In geographic atrophy, there is a primary loss of RPE, followed by the choriocapillaris, while the vessels that survive are severely narrowed. In aging macula, the choriocapillaris density decreases by 45% in 10th decade and 40–54% of the normal in eyes with AMD, geographic atrophy, or disciform scarring. The peripheral choriocapillaris density remains stable with aging and AMD. As the choriocapillaris supplies oxygen to outer retina, a decrease in its density causes RPE to become ischemic; this favors angiogenesis in wet AMD, where RPE-released VEGF plays a critical role.
Medium-Sized and Large Vessels
These include venules and arterioles of Sattler’s layer and arteries and veins of Haller’s layer (outer) of the choroid. The venules possess an endothelial and a pericyte layer. The arterioles, arteries, and veins possess smooth muscle cells (SMCs; Fig. 2.4 ) in their tunica media; in arterioles, there may be one to two layers of SMCs ( Fig. 2.4A and B ), in small veins and arteries, there are four to five layers of SMCs ( Fig. 2.4C and D ), whereas in large arteries, 8 to 10 layers of SMCs may occur compactly in a concentric manner. Besides, arteries have wavy internal and external elastic membrane, the former lies beneath the endothelium ( Fig. 2.4D and E ), the latter occurs external to the tunica media. Unlike the pericytes, the SMCs do not contact with the vessel endothelium and are lined by their own basal lamina on both sides. They are rich in filaments, mitochondria, plasma membrane caveolae, and dense plaques ( Fig. 2.4B ). They are connected by adherence junctions, desmosomes, and gap junctions. They are richly innervated ( Fig. 2.4F ), especially by adrenergic sympathetic and cholinergic parasympathetic fibers.
