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Delaney Henderson, Jayme R Vianna, Michele Hooper, Spring Farrell, Balwantray C Chauhan; Characterizing morphological changes of RGCs with longitudinal in vivo imaging in a model of experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5527. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell (RGC) death is preceded by retraction of dendrites and an overall loss of dendritic branch complexity. This study longitudinally monitored changes in RGC dendritic complexity and intraocular pressure (IOP) elevation in an experimental model of glaucoma.
Two groups of mice (Thy-1 YFP, line H; Jackson Laboratories, ME) received magnetic microbead injection to elevate IOP, which was measured with a rebound tonometer (Tonolab, Tiolat, Inc., Helsinki, Finland) and compared to the control, untreated fellow eye. Longitudinal in vivo imaging (CSLO; Spectralis Multiline, Heidelberg Engineering) visualized RGCs expressing yellow fluorescent protein (YFP). Sholl analysis (radius of dendritic field, peak number of intersections and area under the curve) was used to quantify changes in dendritic arbors of YFP+ RGCs in in vivo images. Group 1 (11 mice, 26 cells) and group 2 (8 mice, 20 cells) were followed for 2 and 6 months, respectively.
In Group 1 mice, the mean (SD) IOP in the experimental and fellow control eyes was 15.2 (1.1) and 9.8 (0.3) mmHg, respectively. There was no change in the radii of the dendritic fields (170 (27) µm, baseline vs 175 (18) μm, month 2), [BC1] but a decrease in the peak number of intersections (23 (5), baseline vs 20 (3), month 2) and area under the curve (2120 (532), baseline vs 1629 (440), month 2). In Group 2 mice, the mean (SD) IOP in the experimental and control eyes was 12.5 (0.5) and 8.8 (0.1) mmHg, respectively. Maximum IOP (14.0 (0.5) mmHg) was reached at 2 months before gradually decreasing. There was no change in the radii of the dendritic fields (191 (30) µm, baseline vs 191 (43) μm, month 6). The peak number of dendritic intersections decreased (28 (3), baseline vs 24 (3), month 6) and overall complexity was lost (3044 (531), baseline vs 2687 (723), month 6). Mixed effects modelling showed loss of dendritic complexity over the first 2 months (P<0.001) but not over the remaining months (P=0.27).
The results show that although there was no loss of terminal dendrites, there was a loss of inner neurites, which contributed to a loss in overall dendritic complexity. The IOP elevation contributed to a loss of complexity to 2 months but did not cause further damage. These findings show that even modest IOP elevation causes changes in dendritic structure in RGCs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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