Changes in vitreal protein profile and retina mRNAs in Reeler mice: NGF, IL33 and Müller cell activation

PLoS One. 2019 Feb 27;14(2):e0212732. doi: 10.1371/journal.pone.0212732. eCollection 2019.

Abstract

A possible link between Nerve Growth Factor (NGF) and Reelin might take place during impaired retinal development occurring in the Reelin deficient mouse model (Reeler). To better characterize NGF and retina impairments at the Reeler retina, vitreous and retina were investigated by means of protein expression and glial cell activation. Reeler (n = 9; RELN-/-) and WT (n = 9; wild-type RELN+/+, B6C3Fe) mice were analyzed at 14, 21 and 28 postnatal days (p). Retinas and vitreous were subjected to confocal analysis and protein array, followed by conventional analysis. A significant increase of NGF, IL33 and TIMP1, a trend to a decrease of IL12 and IL6, as well as a significant decrease of NT3 were detected in Reeler vitreous, particularly at p28 (p<0.05). MIP3β mRNA was decreased while IL33mRNA was significantly upregulated in Reeler retina. Increased number of GFAP+ and Nestin+ cells as well as upregulation of Glutamine Synthetase and Nestin mRNAs were observed in Reeler retinas (p<0.05). These findings extend our previous studies on Reeler retina showing a selective Müller cell activation. NGF and IL33 release into vitreous would suggest a local activation of Müller cells, in addition to retinal ganglion and accessory cells. Overall, the data from this experimental study would strength the potential neuroprotective role played by activated Muller cells through NGF release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Ependymoglial Cells / physiology*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Interleukin-33 / metabolism
  • Mice
  • Mice, Neurologic Mutants
  • Models, Animal
  • Nerve Growth Factor / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • RNA, Messenger / metabolism
  • Reelin Protein
  • Retina / cytology
  • Retina / growth & development*
  • Retina / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Up-Regulation
  • Vitreous Body / metabolism*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Il33 protein, mouse
  • Interleukin-33
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Reelin Protein
  • Nerve Growth Factor
  • Reln protein, mouse
  • Serine Endopeptidases

Grants and funding

This work was supported by: BOB, GE and AM: Italian Ministry of Health acc. number: RC2635302; RM and FK: Italian Ministry of Education acc. number: PRIN 2009P9CE2R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.