# Age-Dependent Redistribution of the Life-Important Enzyme in the Retina: Adult Müller Glial Cells’ Endfeet Lack Spermine Synthase Expression

## TL;DR

This study shows how the enzyme that makes spermine changes its location in the retina as rats grow, with glial cells not producing it but possibly taking it up.

## Contribution

The paper reveals age-dependent redistribution of spermine synthase in retinal cells and suggests glial cells uptake spermine via a transporter.

## Key findings

- Spermine synthase is widely expressed in neonatal retinal neuroblasts but absent in Müller cells.
- Spermine synthase expression shifts to neurons by postnatal day 21 and to synaptic areas by day 120.
- Western blot analysis shows decreased spermine synthase expression as retinas mature.

## Abstract

Polyamine (PA) spermine (SPM) (i) plays an essential role in the function of neurons, while (ii) accumulating predominantly in glial cells by an unknown mechanism. In addition, the translocation of SPM synthesis and redistribution in the developing and maturating retinas remains unclear. Therefore, the expression of the SPM-synthesizing enzyme, spermine synthase (SpmS), was compared in rat retinas on postnatal days 3, 21, and 120 using immunocytochemistry, Western blot (WB), and ImageJ analyses. The anti-glutamine synthetase (GS) antibody identified glial cells, and DAPI labeled the cell nuclei. At postnatal day 3 (P3), the neonatal retina shows widespread SpmS expression throughout most neuroblast cells, but absent in the developing synaptic layers and Müller cell (MCs) processes. By day 21 (P20), SpmS becomes strongly expressed in neurons, and not in glia. On day 120 (P120), SpmS was observed in synaptic areas, with significantly less presence in neuronal soma and still none in MCs. WBs showed a decrease in SpmS expression during maturation. Therefore, glial cells do not synthesize SPM, and the accumulation of SPM in MCs found earlier suggests that glial cells take up SPM via a hypothetical high-affinity SPM transporter. In glia, SPM regulates glial connexin (Cx43) and potassium (Kir4.1) channels, being a key player in CNS diseases and aging.