Purpose: Reelin is expressed in the retina as well as in injured cornea, in concert with several growth factors such as NGF. Reelin absence leads to abnormal retinal development (including migration, differentiation and plasticity) and loss of rod Bipolar cells (RBPs). The aim of this study was to assess whether NGF pathway is affected in reeler mice, by analyzing NGF and trkANGFR-p75NTR expression in all retinal cells. Methods: Reeler-L7-EGFP were obtained from B6C3Fe-a/a-rl X C57/BL6J that were backcrossed to N generation. C57/BL6J and L7-EGFP strains were used as controls. Eyes were obtained from anaesthetised mice on postnatal day 21 and processed for NGF, trkANGFR and p75NTR analysis. Reeler status was verified by genotyping. Confocal images were acquired and mean fluorescence intensities were recorded for statistical analysis. Real time PCR was carried out to evaluate differences in molecular expression. Green fluorescent protein (GFP) was used to identify RBPs in both reeler (rl/rl) and wild type (+/+) retinas. Results: Retinas from both rl/rl and +/+ mice showed specific GFP fluorescence localized in the dendrites, soma and axon terminals of RBPs. The typical appearance of RBPs populating the inner neuronal layer was affected in rl/rl as compared to +/+ mice. A reduced dendrite length and number of synapses were detected in RBPs populating rl/rl retina, as compared to +/+ retina. A selective increase of p75NTR expression was observed in most of RBPs, some Retinal Ganglion Cells (RGCs) and amacrine cells, as compared to +/+, and validated by real time PCR. trkANGFR expression was found slightly decreased. p75NTR/trkANGFR ratio was markedly increased, indicating a selective shift to p75NTR expression in the retina of reeler mice. Most rl/rl RGCs showed a specific NGF immunoreactivity, in comparison to +/+. Conclusions: Our study shows a decrease in dendritic length and a selective p75NTR over-expression in RBPs, which might be interpreted as a tentative of cell rescue. The selective NGFover-expression in RGC close-to RBP and amacrine cells might be consistent with this hypothesis. From these studies, Reeler mice appear to be a good model for exploring the cross-talk between NGF and Reelin in development/maintenance of a normal retinal function. The complete characterization of NGF pathway in reeler mice might provide further information on RBP and RGC cross-talk during normal and pathological conditions.
|Titolo della pubblicazione ospite||ARVO Annual Meeting (MIAMI, USA)|
|Stato di pubblicazione||Pubblicato - 2012|
|Evento||ARVO Annual Meeting - MIAMI (USA)|
Durata: 6 mag 2012 → 10 mag 2012
|Convegno||ARVO Annual Meeting|
|Periodo||6/5/12 → 10/5/12|
- Reelin and NGF