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.
Highlights
The absence of Reelin–a glycoprotein crucial for physiological retinogenesis–has been recently associated with changes in both Nerve Growth Factor (NGF) protein and mRNA in the retina [1,2,3]
At p14, changes for NGF (-4.45 Fold Changes or 2 (FC); p>0.05) and IL33 (-3.57 FC; p>0.05) expression were observed in Reeler vitreous with respect to WT
The finding reported reinforce the observation that NGF might be a compensatory effector of Reelin deficiency during postnatal brain and retinal development
Summary
The absence of Reelin–a glycoprotein crucial for physiological retinogenesis–has been recently associated with changes in both Nerve Growth Factor (NGF) protein and mRNA in the retina [1,2,3]. NGF and Reelin have been reported to take actively part in neurogenesis and retinogenesis [4,5,6]. NGF has been hypothesized to interact with Reelin by modulating neuronal migration, neurodevelopment and other physiological processes in the central nervous system and retina [1,2,7]. NGF activities encompass cell proliferation, cytoskeletal reorganization, migration, differentiation, survival and/or apoptosis [4,8].
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