Other signaling molecules that may be important in lens regeneration are the hedgehog proteins and their receptors, Patched 1 and 2. In the developing eye, Sonic hedgehog (Shh) is expressed in the ganglion cell layer of the retina. Indian hedgehog (Ihh) is expressed exclusively in PECS, and desert hedgehog (Dhh) is expressed in PECs and the neural retina. The patched receptors are also expressed in these tissues. Perturbing the Shh signal transduction pathway in various ways (mutations, inhibitors, overexpression) results in eye defects (Sasagawa et al., 2002; Perron et al., 2003; Tsonis et al., 2004). The patched receptors are found in the lens and in the dorsal and ventral iris of the intact eye in the adult newt. Neither Ihh nor Shh are found in the adult lens, nor is Shh found in the dorsal or ventral iris of the intact eye. However, Ihh is expressed in both dorsal and ventral iris. During lens regeneration, shh and ihh transcripts are found in both the dorsal and ventral iris and in the lens vesicle (Tsonis et al., 2004). Inhibition of the hedgehog pathway by implanting beads impregnated with KAAD (3-keto, N-amino-ethyl aminocaproyl dihydrocinnamoyl) or pellets of mammalian cells transiently expressing hedgehog interacting protein (HIP) prevent lens regeneration completely or allow the formation of only a small vesicle that does not undergo fiber differentiation. Currently, the exact function of hedgehog proteins in lens regeneration is unknown, but given their role in stem cell renewal and proliferation (Chapter 1), it is likely that they play a similar role in lens regeneration.
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