Introduction

The retina contains a rich variety of transmitters and related signaling molecules, including neuroactive peptides and growth factors. Peptides and growth factors have multiple roles in the retina, including participation in cellular signaling and slow synaptic transmission that contribute to visual function (Akopian et al., 2000; Savchenko et al., 2001; Veruki and Yeh, 1992; Zalutsky and Miller, 1990b). Evidence for abundant peptide expression in the vertebrate retina began with descriptions in the late 1970s of peptide activity and peptide receptor binding sites in retinal extracts and peptide immunoreactivity in amacrine cells (Brecha, 1983). Peptides are generally localized to wide-field amacrine cells, which form low-density cell populations that likely have a wide influence on other retinal neurons. A few peptides (e.g., pituitary adenylate cyclase activating polypeptide [PACAP] and substance P [SP]) are also localized to ganglion cells in some species (Brecha et al., 1987; Cuenca et al., 1995; Hannibal et al., 1997). More recently, peptide receptor mRNAs and immunoreactivity have been identified in retinal extracts and localized to multiple retinal cell types (Casini et al., 1997; Johnson et al., 2000; Tsuchida et al., 1990). Interestingly, there is often a difference between the localization of peptide-containing cells and processes, and the cellular distribution of their receptors, suggesting that peptides act in a paracrine manner and therefore have a broad influence on retinal circuits in both the outer and inner retina. Peptides can influence transmitter release from the retina (Bruun and Ehinger, 1993), and they modulate the cellular activity of multiple retinal neurons (Akopian et al., 2000; Feigenspan and Bormann, 1994; Zalutsky and Miller, 1990a). In general, peptide actions are characterized as being slow in onset, long lasting, and potent at low concentrations. Recent cellular studies have shown that peptides influence multiple intracellular effectors, including cAMP and Ca²⁺, and that they modulate K⁺ and Ca²⁺ currents and GABA_A receptor currents in retinal neurons (Akopian et al., 2000; Bruun et al., 1994; Feigenspan and Bormann, 1994; Johnson et al., 2001). Peptides, therefore, influence the efficacy of synaptic transmission in the retina by regulating cellular excitability as well as by modulating the release of GABA and glutamate from presynaptic axonal terminals. Peptide actions are too slow to participate in light-activated responses, and since their actions are long lasting, peptides are likely to have an important role in adaptive mechanisms, such as light and dark adaptation. Together, these findings provide strong support for a functional role of peptides in the retina.

This chapter is mainly focused on neuropeptide Y (NPY), PACAP, SP, somatostatin (SRIF), and vasoactive intestinal polypeptide (VIP) as examples of peptides that are expressed in and affect the mammalian retina via the activation of selective receptors (Table 22.1). These peptides are characterized by a widespread distribution and abundant expression in the peripheral and central nervous system, where they provoke a broad spectrum of biological actions (Arimura, 1998; Gozes and Brenneman, 1989; McDonald, 1988; Otsuka and Yoshioka, 1993; Patel, 1999).