Ординатура / Офтальмология / Английские материалы / Macular Degeneration_Penfold, Provis_2005

Contents

1.2Anatomy of the Old

and New World Monkey Fovea: What Are the Differences

with Human Foveas? 14

1.3What Are the Anatomical Requirements to Create a Fovea? 17

1.3.5Vascular Specializations 19 References 20

1.1

Anatomy of the Human Fovea

1.1.1

General Anatomy

The fovea centralis is a characteristic feature of all primate retinas except the nocturnal New World owl monkey Aotes. It lies on the temporal side of the optic disc within the area centralis or

macular region which is outlined by the superior and inferior temporal branches of the central retinal artery and vein (Fig. 1.1). The fovea lies on the visual axis of the eye such that a beam of light passing perpendicularly through the center of the lens will fall on the fovea. The fovea has long been recognized as the site of maximal visual acuity (Helmholz 1924). Although the fovea only occupies 0.02% of the total retinal area and contains 0.3% of the total cones, it contains 25% of the ganglion cells (Curcio and Allen 1990; Curcio et al. 1990), illustrating its importance in primate vision. A large portion of the central visual centers is devoted to processing foveal information. For instance, 40% of the primary visual cortex processes the central 5° of the visual field which is approximately the retinal area of the foveal pit (Tootell et al. 1988; Curcio et al. 1990). A major function of the superior colliculus, pretectum, cranial nerve nuclei of III, IV, and VI and associated centers is to integrate cortical information and retinal input so that eye movements keep a point in space focused on the fovea of both eyes to facilitate binocular high-acuity vision (Goldberg 2000).

The macular region contains a yellow pigment which is particularly intense around the fovea (Delori et al. 2001). The fovea also is identified by the foveal pit which indents the vitreal surface of the retina (Fig. 1.2). This pit and the concentration of yellow pigment around it (“yellow spot” or “macula lutea”) were recognized in human and monkey retina by anatomists such as Buzzi, Soemmerring, and Fragonard in the late eighteenth century (cited in Polyak 1941). Although Ramon y Cajal made

Fig. 1.1.

The central human retina or macula, with an idealized view of its blood vessels. The optic disc (OD) is to the left. The macula is subdivided into the central-most foveola, which is surrounded in turn by the fovea, parafovea and wider perifovea. Each is indicated by concentric circles. Blood vessels form a ring outlining the foveal avascular zone, which marks the inner limits of the foveal pit

Fig. 1.2. Modification of a drawing of the macaque monkey foveola and foveal slope from Polyak (1941). A cone with an outer and inner segment in the foveola is filled in to show the length of the cone axon and displacement of the synaptic pedicle (P) from the cell body. The arrow

on the right indicates the capillaries forming the wider inner portion of the foveal avascular zone and the arrow on the left the narrower outer ring of capillaries of the foveal avascular zone. The markings on the lower scale each indicate 100 µm

significant advances in our understanding of general retinal cellular anatomy and connectivity using the Golgi impregnation method (Cajal 1892), it was the work of Stefan Polyak (1941) and Brian Boycott and John Dowling (1969), also using Golgi impregnation, which revealed

the intricate relationships of primate retinal neurons, including those forming the fovea. The high-resolution anatomical relationship between neurons and glia within the human and monkey fovea also has been described using electron microscopy (Dowling 1965; Missot-

ten 1965, 1974; Yamada 1969; Borwein et al. 1980; Schein 1988; Krebs and Krebs 1991).

In the adult human eye (Fig. 1.1), the fovea centralis lies 4 mm temporal and 0.8 mm inferior to the center of the optic disc (Hogan et al. 1971). The human foveal pit generally is round, approximately 1000 µm at its widest, and 200–240 µm deep (Fig. 1.2). This is about half the thickness of adjacent retina, as can be seen in Fig. 1.3A. All of these dimensions can vary slightly between individuals (Polyak 1941) and also are subject to the methods used to preserve and examine the fovea. A study of many species of New World monkeys finds that, despite a fivefold variation in eye size and retinal area, the dimensions of the fovea remain constant (Franco et al. 2000). This strongly suggests that the same basic mechanism(s) must operate in all primates to create this stable structure.

The central retina or macula is divided into four concentric zones (Fig. 1.1), with the foveola in the center surrounded in turn by the fovea, parafovea, and perifovea. The centralmost region of the pit is called the foveola (Figs. 1.2, 1.3A,B,G). Here the center of the pit is slightly flattened and is overlain by the highest cone density in the retina. The foveola is 250–350 µm in diameter and represents the central 1° 20b of the visual field.At its thinnest point, the cellular portion of the foveola is slightly more than 100 µm thick and is formed only by cone cell bodies surrounded by Müller glial cell processes (Yamada 1969; Burris et al. 2002). However the foveola has the longest outer and inner segments in the retina and these indent the cellular layers, forming an inward curve called the fovea externa (Fig. 1.3A,G). The inner retinal layers of the foveola, including the outer plexiform layer, are moved laterally onto the foveal slope, although occasional neurons are found on the foveal floor (Röhrenbeck et al. 1989; Curcio and Allen 1990). The fovea (Figs. 1.1, 1.2, 1.3C,F) includes the adjacent 750 µm around the foveola, making it 1.85 mm wide or 5.5° of the central visual field. The fovea contains all of the layers of the retina, including the thickest part, which is called the foveal slope. This region is characterized histologically by having a layer of ganglion cells up to eight deep and a very thick outer plexiform layer. Most of this layer is made up

by the elongated cone axons called the fibers of Henle, but it also contains the synaptic pedicles of the foveolar cones (Figs. 1.2, 1.3C,F). Rods first appear in the fovea and also have elongated axons (Fig. 1.3D,E). These long photoreceptor axons are diagrammatically shown for a single foveolar cone in Fig. 1.2 and indicated by arrows in Fig. 1.3E. They are formed during pit development to allow foveal photoreceptors to retain their synaptic connections to bipolar and horizontal cells during the peripheral-ward displacement of inner retinal neurons and the cen- tral-ward displacement of photoreceptors (Hendrickson 1992; Provis et al. 1998). Capillaries are present in the inner retina up to the foveal slope, where they form a foveal avascular zone (FAZ, see Fig. 1.4A) about 400–500 µm wide (Figs. 1.1, 1.2, 1.4). Two more peripheral zones are identified around the fovea but these do not have sharp boundaries. The region next to the fovea is the parafovea, a zone about 500 µm wide (Figs. 1.1, 1.3D). It also has a thick outer plexiform layer and rods are more numerous. The ganglion cell layer is still eight cells thick near the fovea but decreases to four cells thick at the peripheral edge of the parafovea. The remainder of the central retina is called the perifovea, which is 1.5 mm wide with the peripheral perifoveal edge close to the nasal side of the optic disc (Figs. 1.1, 1.3E). The perifovea ganglion cell layer decreases to one cell thick at its peripheral edge. The perifovea contains many more rods than cones in its outer nuclear layer.

1.1.2

Photoreceptor Distribution, Types, and Numbers in the Human Retina

The fovea is the center of photoreceptor topography in the primate retina. The first quantitative analysis of the human photoreceptor layer was done by Osterberg (1935), using sections from a single celloidin-embedded 16-year-old eye. The advantages of immunocytochemical labeling of specific photoreceptor types combined with recent advances in optical imaging and computerized counting of retinal wholemounts have been used by Curcio and col-

leagues (Curcio et al. 1990, 1991) to considerably extend that pioneering effort.

The mean number of photoreceptors per eye based on a sample of seven human retinas between 27 and 44 years old (Curcio et al. 1990) is 4.6 million cones and 92 million rods, which is slightly lower than the 6 million cones found

by Osterberg (1935). Cones can be differentiated from rods on the basis of size, allowing the creation of color-coded computer-generated maps for cone (Fig. 1.5A) and rod (Fig. 1.5B) distribution in human retina. Different types of photoreceptors have been identified using immunocytochemical labels. Each photoreceptor