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Spermidine Synthase Localization in Retinal Layers: Early Age Changes
Astrid Zayas-Santiago1, Christian J Malpica-Nieves2, David S Ríos3
1Department of Pathology and Laboratory Medicine, Universidad Central del Caribe, Bayamón, PR 00956, USA.
Abstract:
Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the SPD-synthesizing enzyme spermidine synthase (SpdS) in Müller glia and age-dependent SpdS activity are not known. We used immunocytochemistry, Western blot (WB), and image analysis on rat retinae at postnatal days 3, 21, and 120. The anti-glutamine synthetase (GS) antibody was used to identify glial cells. In the neonatal retina (postnatal day 3 (P3)), SpdS was expressed in almost all progenitor cells in the neuroblast. However, by day 21 (P21), the SpdS label was pronouncedly expressed in multiple neurons, while GS labels were observed only in radial Müller glial cells. During early cell adulthood, at postnatal day 120 (P120), SpdS was observed solely in ganglion cells and a few other neurons. Western blot and semi-quantitative analyses of SpdS labeling showed a dramatic decrease in SpdS at P21 and P120 compared to P3. In conclusion, the redistribution of SpdS with aging indicates that SPD is first synthesized in all progenitor cells and then later in neurons, but not in glia. However, MCs take up and accumulate SPD, regardless of the age-associated decrease in SPD synthesis in neurons.
Insights
Spermidine (SPD) synthesis decreases in aging rat retinas, shifting from progenitor cells to neurons. Müller retinal cells accumulate SPD despite reduced synthesis, highlighting their role in managing polyamine levels.
Area of Science:
- Neuroscience
- Cell Biology
- Aging Research
Background:
- Polyamine spermidine (SPD) is vital for aging processes.
- SPD accumulates in Müller retinal cells (MCs), but SPD synthesis in these cells and its age-dependent changes are unknown.
Purpose of the Study:
- To investigate the expression and activity of spermidine synthase (SpdS), the SPD-synthesizing enzyme, in Müller glia and across different age points in the rat retina.
- To understand the role of Müller glia in SPD metabolism during aging.
Main Methods:
- Immunocytochemistry and Western blot (WB) were used to analyze SpdS expression in rat retinae at postnatal days 3, 21, and 120.
- Glutamine synthetase (GS) antibody was employed to identify Müller glial cells.
Main Results:
- SpdS was initially expressed in neonatal retinal progenitor cells (P3).
- By P21, SpdS expression shifted to neurons, while Müller glia (identified by GS) showed minimal SpdS.
- SpdS levels significantly decreased in P21 and P120 retinae compared to P3.
- Müller cells consistently accumulated SPD irrespective of age-related synthesis decline.
Conclusions:
- SpdS redistribution with aging indicates SPD synthesis occurs in progenitor cells and later in neurons, but not in Müller glia.
- Müller retinal cells actively uptake and accumulate SPD, playing a crucial role in retinal polyamine homeostasis during aging.
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