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Evidence for a functional adrenomedullin signaling pathway in the mouse retina.

Blom J, Giove TJ, Pong WW, Blute TA, Eldred WD - Mol. Vis. (2012)

Bottom Line: We found that calcitonin-receptor-like receptor and receptor activity modifying protein 2 had localization patterns similar to ADM, especially in somata in the inner nuclear and ganglion cell layers.These results are the first to show that ADM and functional ADM receptors are present in the retina.Since ADM is increased in eyes with ocular pathologies such as diabetic retinopathy, glaucoma, retinitis pigmentosa, and uveitis, the ADM signaling pathway may provide a new target for ameliorating these retinal pathologies.

View Article: PubMed Central - PubMed

Affiliation: Boston University, Laboratory of Visual Neurobiology, Department of Biology, Boston, MA 02215, USA.

ABSTRACT

Purpose: Adrenomedullin (ADM) is a small, secreted peptide often associated with vasodilation. However, ADM can also function as a neurotransmitter/neuromodulator, and studies suggest ADM is upregulated in the eye in several ocular diseases. However, no studies to date have described an ADM signaling pathway in the retina.

Methods: PCR, immunocytochemistry, nitric oxide imaging, western blots, and a nitrite assay were used to determine the localization of the components of the ADM signaling pathway in the mouse retina.

Results: We used reverse-transcriptase polymerase chain reaction to show that ADM and its primary receptor, calcitonin-receptor-like receptor, along with its associated receptor activity modifying proteins 2 and 3 are expressed in the retina. Using immunocytochemistry, we detected ADM staining throughout the retina in the photoreceptor outer segments, the outer nuclear layer, Müller and amacrine cell somata in the inner nuclear layer, and some somata in the ganglion cell layer. We found that calcitonin-receptor-like receptor and receptor activity modifying protein 2 had localization patterns similar to ADM, especially in somata in the inner nuclear and ganglion cell layers. Finally, we showed that the ADM receptor was functional in the retina. Stimulation of isolated retinas with ADM increased cyclic adenosine monophosphate- and cyclic guanosine monophosphate-like immunoreactivity, as well as nitric oxide production.

Conclusions: These results are the first to show that ADM and functional ADM receptors are present in the retina. Since ADM is increased in eyes with ocular pathologies such as diabetic retinopathy, glaucoma, retinitis pigmentosa, and uveitis, the ADM signaling pathway may provide a new target for ameliorating these retinal pathologies.

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Related in: MedlinePlus

Summary of the cellular localization of the ADM signaling pathway in the retina. ADM was present near the outer segments (OS), in somata in the INL and the GCL, and in Müller cells. CRLR and RAMP2 were present near the OS, and in somata in the ONL, INL, and GCL. ADM, CRLR, and RAMP2 were colocalized near the OS, and in somata in the INL and the GCL.
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f9: Summary of the cellular localization of the ADM signaling pathway in the retina. ADM was present near the outer segments (OS), in somata in the INL and the GCL, and in Müller cells. CRLR and RAMP2 were present near the OS, and in somata in the ONL, INL, and GCL. ADM, CRLR, and RAMP2 were colocalized near the OS, and in somata in the INL and the GCL.

Mentions: Although the CRLR/RAMP2 receptor complex would clearly be functional when it is inserted into the cell membrane, there can also be unique intracellular punctate localization of RAMP2 (Figure 9). The binding of agonists often leads to the rapid internalization of many cell surface G-protein coupled receptors, including adrenomedullin binding to CRLR/RAMP2 receptors [18]. This internalized receptor is then incorporated into endosomes and then degraded. The punctate labeling we see might represent RAMP2 within endosomes.


Evidence for a functional adrenomedullin signaling pathway in the mouse retina.

Blom J, Giove TJ, Pong WW, Blute TA, Eldred WD - Mol. Vis. (2012)

Summary of the cellular localization of the ADM signaling pathway in the retina. ADM was present near the outer segments (OS), in somata in the INL and the GCL, and in Müller cells. CRLR and RAMP2 were present near the OS, and in somata in the ONL, INL, and GCL. ADM, CRLR, and RAMP2 were colocalized near the OS, and in somata in the INL and the GCL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369892&req=5

f9: Summary of the cellular localization of the ADM signaling pathway in the retina. ADM was present near the outer segments (OS), in somata in the INL and the GCL, and in Müller cells. CRLR and RAMP2 were present near the OS, and in somata in the ONL, INL, and GCL. ADM, CRLR, and RAMP2 were colocalized near the OS, and in somata in the INL and the GCL.
Mentions: Although the CRLR/RAMP2 receptor complex would clearly be functional when it is inserted into the cell membrane, there can also be unique intracellular punctate localization of RAMP2 (Figure 9). The binding of agonists often leads to the rapid internalization of many cell surface G-protein coupled receptors, including adrenomedullin binding to CRLR/RAMP2 receptors [18]. This internalized receptor is then incorporated into endosomes and then degraded. The punctate labeling we see might represent RAMP2 within endosomes.

Bottom Line: We found that calcitonin-receptor-like receptor and receptor activity modifying protein 2 had localization patterns similar to ADM, especially in somata in the inner nuclear and ganglion cell layers.These results are the first to show that ADM and functional ADM receptors are present in the retina.Since ADM is increased in eyes with ocular pathologies such as diabetic retinopathy, glaucoma, retinitis pigmentosa, and uveitis, the ADM signaling pathway may provide a new target for ameliorating these retinal pathologies.

View Article: PubMed Central - PubMed

Affiliation: Boston University, Laboratory of Visual Neurobiology, Department of Biology, Boston, MA 02215, USA.

ABSTRACT

Purpose: Adrenomedullin (ADM) is a small, secreted peptide often associated with vasodilation. However, ADM can also function as a neurotransmitter/neuromodulator, and studies suggest ADM is upregulated in the eye in several ocular diseases. However, no studies to date have described an ADM signaling pathway in the retina.

Methods: PCR, immunocytochemistry, nitric oxide imaging, western blots, and a nitrite assay were used to determine the localization of the components of the ADM signaling pathway in the mouse retina.

Results: We used reverse-transcriptase polymerase chain reaction to show that ADM and its primary receptor, calcitonin-receptor-like receptor, along with its associated receptor activity modifying proteins 2 and 3 are expressed in the retina. Using immunocytochemistry, we detected ADM staining throughout the retina in the photoreceptor outer segments, the outer nuclear layer, Müller and amacrine cell somata in the inner nuclear layer, and some somata in the ganglion cell layer. We found that calcitonin-receptor-like receptor and receptor activity modifying protein 2 had localization patterns similar to ADM, especially in somata in the inner nuclear and ganglion cell layers. Finally, we showed that the ADM receptor was functional in the retina. Stimulation of isolated retinas with ADM increased cyclic adenosine monophosphate- and cyclic guanosine monophosphate-like immunoreactivity, as well as nitric oxide production.

Conclusions: These results are the first to show that ADM and functional ADM receptors are present in the retina. Since ADM is increased in eyes with ocular pathologies such as diabetic retinopathy, glaucoma, retinitis pigmentosa, and uveitis, the ADM signaling pathway may provide a new target for ameliorating these retinal pathologies.

Show MeSH
Related in: MedlinePlus