https://doi.org/10.4081/ejh.2022.3373

Secreted key regulators (Fgf1, Bmp4, Gdf3) are expressed by PAC1-immunopositive retinal ganglion cells in the postnatal rat retina

Vol. 66 No. 2 (2022)
Submitted: 17 December 2021
Accepted: 2 March 2022
Published: 27 April 2022
PAC1 receptor, Fgf1, Bmp4, Gdf3, retinal ganglion cell
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Authors

Viktória Dénes
vdenes@gamma.ttk.pte.hu
Department of Experimental Zoology and Neurobiology, University of Pécs, Hungary.
Kármen Kovacs
Department of Experimental Zoology and Neurobiology, University of Pécs, Hungary.
Ákos Lukáts
Department of Experimental Zoology and Neurobiology, University of Pécs; Department of Translational Medicine, Semmelweis University, Budapest, Hungary.
Adrienn Mester
Department of Experimental Zoology and Neurobiology, University of Pécs, Hungary.
Gergely Berta
Institute of Medical Biology, School of Medicine, University of Pécs, Hungary.
Arnold Szabó
Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
Robert Gabriel
Department of Experimental Zoology and Neurobiology, University of Pécs, Hungary.

Identified as a member of the secretin/glucagon/VIP superfamily, pituitary adenylate cyclase-activating polypeptide (PACAP1-38) has been recognized as a hormone, neurohormone, transmitter, trophic factor, and known to be involved in diverse and multiple developmental processes. PACAP1-38 was reported to regulate the production of important morphogens (Fgf1, Bmp4, Gdf3) through PAC1-receptor in the newborn rat retina. To follow up, we aimed to reveal the identity of retinal cells responsible for the production and secretion of Fgf1, Bmp4, and Gdf3 in response to PACAP1-38 treatment. Newborn (P1) rats were treated with 100 pmol PACAP1-38 intravitreally. After 24 h, retinas were dissected and processed for immunohistochemistry performed either on flat-mounted retinas or cryosections. Brn3a and PAC1-R double labeling revealed that 90% of retinal ganglion cells (RGCs) expressed PAC1-receptor. We showed that RGCs were Fgf1, Bmp4, and Gdf3-immunopositive and PAC1-R was co-expressed with each protein. To elucidate if RGCs release these secreted regulators, the key components for vesicle release were examined. No labeling was detected for synaptophysin, Exo70, or NESP55 in RGCs but an intense Rab3a-immunoreactivity was detected in their cell bodies. We found that the vast majority of RGCs are responsive to PACAP, which in turn could have a significant impact on their development or/and physiology. Although Fgf1, Bmp4, and Gdf3 were abundantly expressed in PAC1-positive RGCs, the cells lack synaptophysin and Exo70 in the newborn retina, thus unable to release these proteins. These proteins could regulate postnatal RGC development acting through intracrine pathways.

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Ethics Approval

All procedures were approved by the Ethical Committee of the University of Pécs, Hungary, and the Animal Health and Animal Welfare Directorate of the National Food Chain Safety Office of the Hungarian State (BA/35/51-58/2016)

Rights

TKP2021-EGA-16 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme. The work has also been supported by EFOP 3.6.-2-16-2017-0008 and NKFIH 119 289.

How to Cite

Dénes, V., Kovacs, K., Lukáts, Ákos, Mester, A., Berta, G., Szabó, A., & Gabriel, R. (2022). Secreted key regulators (Fgf1, Bmp4, Gdf3) are expressed by PAC1-immunopositive retinal ganglion cells in the postnatal rat retina. European Journal of Histochemistry, 66(2). https://doi.org/10.4081/ejh.2022.3373
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