Info

(R)

Sarthy et al., 1991

Merosin

±

(R)

Morissette and Carbonetto, 1995

Slaminin

±

(R)

Hunter et al., 1992

Tenascin

±

(R)

Barsch et al., 1992; Perez and Halfter, 1993

Thrombospondin

±

(R)

Neugebauer et al., 1991

Vitronectin

±

(R)

Neugebauer et al., 1991

Chondroitin sulfate

±

(R)

Morris et al., 1987; Snow et al., 1991; Brittis et al., 1992; McAdams and McLoon, 1995

Heparan sulfate

±

(R)

Halfter and Schurer, 1994; Chai and Holt, 1997

Keratan sulfate

±

(R)

McAdams and McLoon, 1995; Holt, 1997

Decorin

±

(R)

Inatani et al., 1999

R, results with retina; C, data from retinal cell cultures; ±, these substances are found in the internal limiting membrane. It is not known whether they are synthesized by Müller cells.

R, results with retina; C, data from retinal cell cultures; ±, these substances are found in the internal limiting membrane. It is not known whether they are synthesized by Müller cells.

tional diversity of ECM molecules is further broadened by their interactions with other kinds of regulatory molecules. Many cell adhesion molecules like NCAM interact with the ECM. Growth factors such as b-FGF bind to the ECM, and their activity and stability appears to be regulated by interactions with the ECM (Hall and Schachner, 1998).

In the developing nervous system, ECM molecules play a vital role in neuronal migration and axonal growth (Reichardt and Tomaselli, 1991; Letourneau et al., 1994). Many ECM molecules are found in both developing and adult retina (Table 2.2). However, neither the function nor the cellular origin of these molecules is well studied. The ECM molecules are generally prominent at the ILM and could be derived from ganglion cells, astrocytes, Müller cells, or the retinal vasculature, all ofwhich abut or are in close proximity to the ILM. Müller cells appear to be a likely source for some of these molecules. However, in situ hybridization studies demonstrate Müller cells do not synthesize either laminin B1 mRNA or collagen lV mRNA during development or in the adult mouse retina (Fig. 2.13; Sarthy et al., 1991; Sarthy, 1993). Whether other ECM molecules such as merosin, vit-ronectin, and thrombospondin present at the ILM are derived from Müller cells remains to be established. On the other hand, two inhibitory ECM molecules, EAP-300 (embryonic avian polypeptide of 300 kDa) and clausterin (a 320 kDa keratan sulfate proteoglycan), are expressed by Müller cells in the developing retina (McCabe and Cole, 1992). EAP-300 and clausterin may be involved in retinal stratification (McCabe and Cole, 1992).

As described previously, cells interact with the extracellular matrix via the integrin family of cell surface receptors. Integrins are heterodimers made up of a and ß subunits each of which belongs to a large subfamily (Reichardt and Tomiselli, 1991; Powell and Kleinman, 1997). Müller cells have been reported to express some integrins (Elner and Elner, 1997). Although we know very little about integrin function in Müller cells, we might speculate that integrins mediate adhesion of the Müller cell end feet to the vitreous collagen (see Chapter 1) , and may also be involved in Müller cell migration into epiretinal membranes (Elner and Elner, 1997).

2.2.5. Growth and Neurotrophic Factors

It is widely recognized that growth and neurotrophic factors serve as important signaling molecules in development of the nervous system. Many of the factors present in the developing CNS are also found in the developing retina (Tanihara et al., 1997) (Table 2.3). Some factors such as TGF- a regulate cell proliferation while others appear to promote neuronal differentiation and survival (Harris, 1997). Indeed, there is growing evidence that

Figure 2.13. Immunolocalization and in situ hybridization data for laminin B1 expression in developing mouse retina. Immunostaining shows that laminin is present at the internal limiting membrane in embryonic retina at E12 (A), E-15 (B), and E-20 (C). It is also present, albeit in a smaller quantity, in the adult retina. In situ hybridization data show that laminin B1 mRNA is not present in Müller cells at P3 (D), P-7 (E), or adult retina (F). The data show that laminin is highly expressed at the INL but the site of laminin synthesis is not the Müller cell. Arrows in A, B, C show internal limiting membrane. Arrowhead, RPE. Nb, neuroblast layer; le, lens; and r, retina. Arrows in D, E, F show ganglion cell bodies (Sarthy and Fu, 1990). (Copyright 1990 The Rockefeller University Press, reprinted with permission.)

Müller cells secrete extrinsic factors that can influence neuronal differentiation and survival.

One of the best examples comes from the studies of Neophytou and associates (1997) who observed that serum had a dramatic effect on rod cell differentiation in cultures of neonatal mouse retina. In medium containing 10% fetal calf serum (FCS), very few rods were observed whereas in cultures

Table 2.3. Cytokines, Growth Factors, and Their Receptors in Retinal Müller Cells

Müller cell Reference

Table 2.3. Cytokines, Growth Factors, and Their Receptors in Retinal Müller Cells

Müller cell Reference

Cytokines/Growth factors

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