Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways

Camila Saggioro de Figueiredo; Ícaro Raony; Simone Vidal Medina; Eliezer de Mello Silva; Aline Araujo Dos Santos; Elizabeth Giestal-de-Araujo

doi:10.1016/j.crneur.2022.100068

Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways

Curr Res Neurobiol. 2022 Dec 16:4:100068. doi: 10.1016/j.crneur.2022.100068. eCollection 2023.

Authors

Camila Saggioro de Figueiredo¹, Ícaro Raony², Simone Vidal Medina¹, Eliezer de Mello Silva¹, Aline Araujo Dos Santos³, Elizabeth Giestal-de-Araujo^{1

4}

Affiliations

¹ Department of Neurobiology and Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói, 24210-200, Brazil.
² Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
³ Department of Physiology and Pharmacology and Program of Neurosciences, Fluminense Federal University, Niterói, 24210-130, Brazil.
⁴ National Institute of Science and Technology on Neuroimmunomodulation - INCT-NIM, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, 21040-360, Brazil.

Abstract

Insulin-like growth factor-1 (IGF-1) plays critical roles in the development of the central nervous system (CNS), including the retina, regulating cell proliferation, differentiation, and survival. Here, we investigated the role of IGF-1 on retinal cell proliferation using primary cultures from rat neural retina. Our data show that IGF-1 stimulates retinal cell proliferation and regulates the expression of neurotrophic factors, such as interleukin-4 and brain-derived neurotrophic factor. In addition, our results indicates that IGF-1-induced retinal cell proliferation requires activation of multiple signaling pathways, including phosphatidylinositol 3-kinase, protein kinase Src, phospholipase-C, protein kinase C delta, and mitogen-activated protein kinase pathways. We further show that activation of matrix metalloproteinases and epidermal growth factor receptor is also necessary for IGF-1 enhancing retinal cell proliferation. Overall, these results unveil potential mechanisms by which IGF-1 ensures retinal cell proliferation and support the notion that manipulation of IGF-1 signaling may be beneficial in CNS disorders associated with abnormal cell proliferation.

Keywords: Cell proliferation; Central nervous system; Epidermal growth factor; Insulin-like growth factor-1; Retina; Signaling pathway.