Insulin receptor signaling is essential for normal photoreceptor differentiation.

RAJALA R.V.S.; RAJALA A.; BRUSH RS; ROTSTEIN N.P.; POLITI L.E.

JOURNAL OF NEUROCHEMISTRY

Wiley Blackwell

Año: 2009 vol. 110 p. 1648 - 1660

0022-3042

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> The insulin receptor (IR) and IR signaling proteins are widely distributed throughout the central nervous system. IR signaling provides a trophic signal for transformed retinal neurons in culture and we recently reported that deletion of IR in rod photoreceptors by Cre/lox system resulted in stress-induced photoreceptor degeneration. These studies suggest a neuroprotective role of IR in rod photoreceptor cell function. However, there are no studies available on the role of insulin-induced IR signaling in the development of normal photoreceptors. To examine the role of insulin-induced IR signaling, we analyzed cultured neuronal cells isolated from newborn rodent retinas. In insulin-lacking cultures, photoreceptors from wild type rat retinas exhibited an abnormal morphology with a wide axon cone and disorganization of the actin and tubulin cytoskeleton. Photoreceptors from IR knockout mouse retinas also exhibited a similar abnormal morphology. A novel finding in this study was that addition of docosahexaenoic acid (DHA), a photoreceptor trophic factor, restored normal axonal outgrowth in insulin-lacking cultures. These data suggest that IR-signaling pathways regulate actin and tubulin cytoskeletal organization in photoreceptors; they also imply that insulin and DHA activate at least partially overlapping signaling pathways that are essential for the development of normal photoreceptors.