Background <p>To observe the therapeutic effects of growth associated protein-43 (GAP 43) gene modified rat bone marrow mesenchymal stem cells (BMSCs) on experimental retinal degeneration.</p> Methods <p>A total of 80 male Royal College of Surgeons (RCS) rats were divided into three groups at postnatal 21 (P21) randomly. A cell suspension of 5 × 104 BMSCs modified with GAP-43 in 2&#xa0;µl PBS was injected into the subretinal space of BMSCs + GAP-43 group rats, BMSCs group rats received5 × 104 BMSCs in 2&#xa0;µl PBS and PBS group rats received 2&#xa0;µl PBS. Photoreceptor necrosis and apoptosis was assessed by HE staining and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) detection. The expression of GAP-43, Glutamine synthetase (GS), rhodopsin (RHO), Caspase-8 and Caspase-9 was analyzed by immunofluorescence, western blot.</p> Results <p>Transplantation of GAP-43-modified BMSCs into the subretinal cavity of RCS rats revealed that: retinal GAP-43 expression was significantly elevated (<i>P</i> &lt; 0.05); Rhodopsin (Rho) expression, a photoreceptor marker, was upregulated 1.5-fold (<i>P</i> &lt; 0.05), and the thickness of the outer nuclear layer increased to 79.78 ± 6.83&#xa0;μm (control 29.92 ± 4.17&#xa0;μm, <i>P</i> &lt; 0.01); The apoptosis rate decreased to 41.9% (control 63.8%, <i>P</i> &lt; 0.01), and Caspase-8/9 activation was inhibited; Müller cell proliferation was reduced (GS decreased, <i>P</i> &lt; 0.05). suggesting that GAP-43-modified BMSCs delayed retinal degeneration through anti-apoptosis and pro-photoreceptor survival.</p> Conclusions <p>The results suggest that GAP-43 gene modified BMSCs has the therapeutic effect on the early stage of retinal degeneration, which might make more photoreceptors preserved.</p> Graphical Abstract <p></p>

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Protection of GAP-43 gene–modified bone marrow mesenchymal stem cells on retinitis pigmentosa

  • Yuxi He,
  • Yuxiao Guo,
  • Guanfang Su

摘要

Background

To observe the therapeutic effects of growth associated protein-43 (GAP 43) gene modified rat bone marrow mesenchymal stem cells (BMSCs) on experimental retinal degeneration.

Methods

A total of 80 male Royal College of Surgeons (RCS) rats were divided into three groups at postnatal 21 (P21) randomly. A cell suspension of 5 × 104 BMSCs modified with GAP-43 in 2 µl PBS was injected into the subretinal space of BMSCs + GAP-43 group rats, BMSCs group rats received5 × 104 BMSCs in 2 µl PBS and PBS group rats received 2 µl PBS. Photoreceptor necrosis and apoptosis was assessed by HE staining and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) detection. The expression of GAP-43, Glutamine synthetase (GS), rhodopsin (RHO), Caspase-8 and Caspase-9 was analyzed by immunofluorescence, western blot.

Results

Transplantation of GAP-43-modified BMSCs into the subretinal cavity of RCS rats revealed that: retinal GAP-43 expression was significantly elevated (P < 0.05); Rhodopsin (Rho) expression, a photoreceptor marker, was upregulated 1.5-fold (P < 0.05), and the thickness of the outer nuclear layer increased to 79.78 ± 6.83 μm (control 29.92 ± 4.17 μm, P < 0.01); The apoptosis rate decreased to 41.9% (control 63.8%, P < 0.01), and Caspase-8/9 activation was inhibited; Müller cell proliferation was reduced (GS decreased, P < 0.05). suggesting that GAP-43-modified BMSCs delayed retinal degeneration through anti-apoptosis and pro-photoreceptor survival.

Conclusions

The results suggest that GAP-43 gene modified BMSCs has the therapeutic effect on the early stage of retinal degeneration, which might make more photoreceptors preserved.

Graphical Abstract