Persistent neurogenesis in the teleost retina: evidence for regulation by the growth-hormone/insulin-like growth factor-I axis.
Based on results from previous studies (J. Comp. Neurol. 394 (1998) 386, 395), it was hypothesized that the persistent neurogenesis in the retina of teleost fish is modulated by insulin-like growth factor-I (IGF-I), which, in turn, is regulated by growth hormone (GH). Two approaches were undertaken to test this hypothesis. First, a variety of techniques were used to determine if IGF-I and the IGF-I receptor (IGF-IR) are expressed in the retina. Second, GH was injected into animals to stimulate IGF-I synthesis in target tissues, and IGF-I expression and cell proliferation in the retina was quantitatively assayed. Reverse transcriptase-polymerase chain reaction, screening a retinal cDNA library and Northern analysis showed that genes encoding IGF-I and IGF-IR are expressed in the retina of goldfish. In situ hybridization showed that IGF-IR is expressed by retinal progenitors and all differentiated retinal neurons. Intraperitoneal injections of GH elevate IGF-I mRNA levels in the liver, brain and retina and produce a dose-dependent change in the proliferation of stem cells and progenitors in the retina. These data indicate that the principal components of the IGF-I signaling cascade are present in the retinas of teleosts, and we suggest these elements mediate the persistent, growth-associated neurogenesis in this tissue.
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Otteson
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Cirenza
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Hitchcock
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006054:Goldfish / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1