The Guinea Pig Retina1

We have studied the anatomical localization, chromatographic properties, and development of somatostatinlike immunoreactivity (SLI) in the guinea pig retina. The majority of guinea pig retinal SLI in the adult and fetus eluted similarly to somatostatin-28 by gel filtration and high pressure liquid chromatography. This represents a higher ratio of somatostatin-%-like material to total SLI than had been observed in retinal extracts from most other animal species. Somatostatin-like-immunoreactive cells and fibers were localized using two antisera in cryostat-sectioned and flat mounted retinae. Distribution of cells and fibers differed uniquely from that in other species previously reported. Reactive perikarya were located only in the far peripheral region: in the innermost layer of the inner nuclear layer (INL), in the inner plexiform layer (IPL), and in the ganglion cell layer. Reactive fibers were prominent in the IPL and nerve fiber layer (NFL) in both the peripheral and central retina. Less frequently, processes were observed between the NFL and IPL, between the IPL and INL, and, rarely, in the outer plexiform layer and outer nuclear layer. Small numbers of reactive fibers were found in the optic nerve and disc. These observations suggest that processes of intrinsic (amacrine or associational ganglion cells) and projection neurons (true ganglion cells or efferent fibers) containing SLI are intermingled in the guinea pig retina. SLI, quantified by radioimmunoassay, was present in the developing retina as early as the 6th week of gestation (full term is 10 weeks). Immunohistochemically detected somatostatin-like-immunoreactive elements were seen first at 2 weeks before birth, coincident with the onset of the period of most rapid increase in levels of assayed SLI. Somatostatin-like-immunoreactive peptides reached two-thirds of adult levels by birth. Coincident with the application of radioimmunoassay (RIA) and immunohistochemical localization techniques to the study of retinal neurotransmitters has come the realization that the retina contains a considerable number of peptides familiar to the gastrointestinal system and to other regions of the brain (reviewed in Brecha and Karten, 1983). A small but steadily growing number of accounts indicates that some peptides have a demonstrable effect on retinal neuronal activity (Dick and Miller, 1981; Djamgoz et al., 1981, 1983; Glickman et al., 1982; i We are indebted to Ms. Marilyn Patten and Mrs. Carol McKeown for their excellent technical assistance and to Mrs. Susan Vos and Ms. Caroline Collins for their skillful typing. Appreciation is extended to Professor W. K. Stell for his critical review of the manuscript. The research was supported by grants to A. W. S. and 0. P. R. from the Medical Research Council of Canada and the Alberta Heritage Foundation for Medical Research. Y. S. is a postdoctoral fellow of the Alberta Heritage Foundation for Medical Research; 0. P. R. is a scholar of the Medical Research Council and the Alberta Heritage Foundation for Medical Research. * To whom correspondence should be addressed, at Department of Anatomy, The University of Calgary, 3330 Hospital Drive N. W., Calgary, Alberta, Canada T2N 4Nl. 3 Present address: Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. Stell et al., 1983). In the mammalian retina five or six of the peptides have been identified. These include somatostatin-like (somatotropin release-inhibiting factor) (reviewed by Rorstad et al., 1980), thyrotropin-releasing hormone-like (Schaeffer et al., 1977), substance P-like (Kanazawa and Jessell, 1976), vasoactive intestinal polypeptide-like (Loren et al., 1980), cholecystokinin-like (Eskay and Beinfeld, 1982), and possibly Metenkephalin-like (Altschuler et al., 1982) peptides. Somatostatin-like substances have been among the most intensively studied retinal neuropeptides. They were first extracted from the mammalian retina and assayed nearly concurrently by Rorstad et al. (1979), Shapiro et al. (1979), Yamada et al. (1980), and Lake and Pate1 (1980). They were found to have the same biological effect on cultured anterior pituitary cells as that derived from the hypothalamus, i.e., an inhibition of the secretion of growth hormone (Rorstad et al., 1979). Retinal somatostatin-like immunoreactivity (SLI) was reduced by chemical lesions of the inner retinal layers in the rat (Lake and Patel, 1980) but not by optic nerve section (Rorstad et al., 1979). Early localization studies in non-mammalian retinas indicated SLI in presumed amacrine cells of the inner nuclear layer (INL), in fibers in sublayers of the inner plexiform layer (IPL), and in cells of the ganglion cell layer (GCL), the general pattern being similar to that seen for other neuropeptides (Yamada et al., 1980; Buckerfield et al., 1981; Ishimoto et al., SAIF 28 Spira et al.