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Vivian Choh, Stacey A Chong, Anita Kumar, Natalie Hutchings, Christine Frances Wildsoet; Enhancement of mitotic activity in the chick retina following optic nerve section and growth factor treatment. Invest. Ophthalmol. Vis. Sci. 2018;59(9):585. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Optic nerve section (ONS) is an experimental model for mechanically damaging retinal ganglion cells (RGCs). It was shown that chick retinas can be stimulated to proliferate following acute damage by chemotoxic injection (Fischer & Reh, 2003: Glia, 43: 70-76) and that mitosis can be enhanced with exogenous growth factors (Fischer & Reh, 2002: Dev Biol, 251: 367-79). This study was undertaken to determine if mechanically-damaged retinas have the ability to proliferate and whether growth factors can enhance proliferation.
1-day-old White leghorn birds underwent optic nerve section (ONS) surgery in one eye and sham ONS surgery in the other eye. Chicks were divided into two groups to determine 1) whether mechanical damage could stimulate mitotic activity (n=32) and 2) whether the addition of a cocktail of growth factors (GFs; 2 µg/ml of insulin + 100 ng of fibroblast growth factor-2) could lead to enhanced proliferation (n=28). Bilateral GF injections were given immediately following the surgeries, and every 3 days thereafter. Bromodeoxyuridine (BrdU; 100 µg/ml) was used to label proliferating cells in the retinas, which were collected at various time points post-ONS.
The number of mitotic cells in the ganglion cell layer (GCL) ranged from 2.2 ± 0.7 cells/mm to 14.1 ± 0.7 cells/mm in ONS-eyes between days 3 to 7 post-ONS, with the highest numbers on days 5 and 6 post-ONS (99% CI). By day 8 post-ONS, no mitotic activity was observed in the ONS-eyes. Sham ONS-eyes did not show BrdU-labelling at any time point. GF-injection was associated with increased mitotic activity in both eyes and mitotic activity persisted beyond 8 days. Peak mitotic activity in GF-injected ONS-eyes occurred at 5 days post-ONS; at this time, the number of mitotic cells in the ONS-eyes (17.9 ± 2.6 cells/mm) was signficantly greater (p<0.05) than that of the GF-injected sham ONS-eyes (4.1 ± 1.7 cells/mm). The combined effect of GFs and ONS on stimulating mitosis was initally synergistic; however, the benefits of the GF were declined with time, becoming negligible by day 7 post-ONS,
Mechanical damage to the RGCs and growth factor injections both lead to stimulation of mitotic activity in the retina. The beneficial effect of combining the treatments is initially synergistic, but becomes lost over time.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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