The location of insulin receptors in bovine retina and isolated retinal cells

Gosbell, Andrew; Favilla, Ian; Jablonski, Paula

doi:10.1046/j.1442-6404.2002.00499.x

Cited by 15 publications

(12 citation statements)

References 41 publications

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“…Akt, like the IR, exhibits high basal phosphorylation and activity in retina in vivo; however, insulin promoted Akt phosphorylation in vivo and increased Akt Ser473 immunoreactivity in the retinal nuclear layers, suggesting that numerous cell types, including photoreceptors and ganglion cells, respond to insulin in the intact retina. This is consistent with the finding of broad IR expression in retinal tissue (22). Akt nuclear translocation has been reported in hippocampal neurons in a cerebral ischemia reperfusion model (72), suggesting that Akt Ser473 phosphorylation is a critical event promoting neuronal survival and that cofactors, such as Tcl1, may also play a significant role in neuronal survival by aiding Akt translocation (46).…”

Section: Discussionsupporting

confidence: 79%

Characterization of insulin signaling in rat retina in vivo and ex vivo

Reiter¹,

Sandirasegarane²,

Wolpert³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

158

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Insulin receptor (IR) signaling cascades have been studied in many tissues, but retinal insulin action has received little attention. Retinal IR signaling and activity were investigated in vivo in rats that were freely fed, fasted, or injected with insulin by phosphotyrosine immunoblotting and by measuring kinase activity. A retina explant system was utilized to investigate the IR signaling cascade, and immunohistochemistry was used to determine which retinal cell layers respond to insulin. Basal IR activity in the retina was equivalent to that in brain and significantly greater than that of liver, and it remained constant between freely fed and fasted rats. Furthermore, IR signaling increased in the retina after portal vein administration of supraphysiological doses of insulin. Ex vivo retinas responded to 10 nM insulin with IR β-subunit (IRβ) and IR substrate-2 (IRS-2) tyrosine phosphorylation and AktSer473 phosphorylation. The retina expresses mRNA for all three Akt isoforms as determined by in situ hybridization, and insulin specifically increases Akt-1 kinase activity. Phospho-AktSer473 immunoreactivity increases in retinal nuclear cell layers with insulin treatment. These results demonstrate that the retinal IR signaling cascade to Akt-1 possesses constitutive activity, and that exogenous insulin further stimulates this prosurvival pathway. These findings may have implications in understanding normal and dysfunctional retinal physiology.

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Section: Discussionsupporting

confidence: 79%

Characterization of insulin signaling in rat retina in vivo and ex vivo

Reiter¹,

Sandirasegarane²,

Wolpert³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

158

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“…All types of retinal cells express insulin receptors, with particularly high expression on Mü ller cell end-feet and neuronal dendrites (42). The net reduction of insulin receptor signaling kinase activities found in this study may reflect changes in all cell types.…”

Section: Diabetes Vol 55 April 2006mentioning

confidence: 74%

Diabetes Reduces Basal Retinal Insulin Receptor Signaling

et al. 2006

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Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-␤ autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

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“…Application of insulin to the in vitro bovine retina preparation decreased the amplitudes of the a-and b-waves of the electroretinogram (29). Insulin receptors are widely expressed in the retina (30), and administration of this hormone modified the permeability of voltage-gated K ϩ and Ca 2ϩ channels through receptor-mediated tyrosine phosphorylation, thus modulating the activity of photoreceptors and Müller cells. The finding, however, that insulin is secreted by neurons within the retina is completely unexpected.…”

Section: Discussionmentioning

confidence: 99%

Gene discovery in genetically labeled single dopaminergic neurons of the retina

Gustincich

Contini

Gariboldi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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In the retina, dopamine plays a central role in neural adaptation to light. Progress in the study of dopaminergic amacrine (DA) cells has been limited because they are very few (450 in each mouse retina, 0.005% of retinal neurons). Here, we applied transgenic technology, single-cell global mRNA amplification, and cDNA microarray screening to identify transcripts present in DA cells. To profile gene expression in single neurons, we developed a method (SMART7) that combines a PCR-based initital step (switching mechanism at the 5 end of the RNA transcript or SMART) with T7 RNA polymerase amplification. Single-cell targets were synthesized from genetically labeled DA cells to screen the RIKEN 19k mouse cDNA microarrays. Seven hundred ninety-five transcripts were identified in DA cells at a high level of confidence, and expression of the most interesting genes was confirmed by immunocytochemistry. Twenty-one previously undescribed proteins were found in DA cells, including a chloride channel, receptors and other membrane glycoproteins, kinases, transcription factors, and secreted neuroactive molecules. Thirty-eight percent of transcripts were ESTs or coding for hypothetical proteins, suggesting that a large portion of the DA cell proteome is still uncharacterized. Because cryptochrome-1 mRNA was found in DA cells, immunocytochemistry was extended to other components of the circadian clock machinery. This analysis showed that DA cells contain the most common clock-related proteins.

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The location of insulin receptors in bovine retina and isolated retinal cells

Cited by 15 publications

References 41 publications

Characterization of insulin signaling in rat retina in vivo and ex vivo

Characterization of insulin signaling in rat retina in vivo and ex vivo

Diabetes Reduces Basal Retinal Insulin Receptor Signaling

Gene discovery in genetically labeled single dopaminergic neurons of the retina

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