June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Delayed neurogenesis of retinal ganglion cells in the albino mouse retina
Author Affiliations & Notes
  • Nefeli Slavi
    Zuckerman Institute, Columbia University, New York, New York, United States
  • Carol Mason
    Zuckerman Institute, Columbia University, New York, New York, United States
    Pathology and Cell Biology, Neuroscience, and Ophthalmology, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Nefeli Slavi, None; Carol Mason, None
  • Footnotes
    Support  NIH R01EY0152901
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3765. doi:
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      Nefeli Slavi, Carol Mason; Delayed neurogenesis of retinal ganglion cells in the albino mouse retina. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3765.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Binocular vision depends on the correct proportion of retinal ganglion cells (RGCs) projecting to the ipsilateral and contralateral side of the brain. In albinism, a decrease in the number of RGCs expressing Zic2, the transcription factor necessary for ipsilateral specification, leads to abnormal distribution of crossed and uncrossed RGC axons and impaired stereo vision. To reveal the developmental steps in the regulation of ipsi- and contralateral RGC properties, we compare the pigmented and albino mouse retina, and examine the cell cycle of neural progenitors and its regulation by CyclinD2 in the ciliary margin zone (CMZ), a neurogenic niche at the embryonic retina periphery.

Methods : Pigmented (Tyr+; P) and albino (Tyrc-2J; A) C57BL/6 mouse embryos were collected from embryonic day (E) 13.5 until E17.5. For birthdating, pregnant mothers were injected with BrdU and EdU with a two-hour interval, and embryos were harvested 30 minutes later. For immunohistochemistry, coronal sections were stained for CyclinD2, PH3, BrdU/EdU and Zic2. Cells were counted using Fiji software. Student’s t-test was used for statistical analyses.

Results : At E13.5 and E14.5, the number of CyclinD2+ cells is reduced in the ventral CMZ of albino mice compared to pigmented littermates (P vs A: E13.5: 170±37 vs 11±43, p=0.02; E14.5: 199±46 125±14, p=0.016; N=6). The number of cells in the G1 phase of the cell cycle is significantly higher in the albino CMZ (P vs A: E13.5: 30±9 vs 57±6, p=0.03; E14.5: 28±8 vs 41±10, p=0.05; N=6), with a concomitant reduction of cells in the S phase (P vs A: E13.5: 191±12 vs 152±5, p=0.001; E14.5: 225±28 vs 160±39, p=0.01; N=6). As a result, fewer mitotic/PH3+ cells are present in the albino compared to pigmented CMZ (P vs A: E13.5: 65±29 vs 38 ±16, p=0.04; E14.5: 64±12 vs 38±10, p=0.004; N=6), and likewise, fewer Zic2+ RGCs reside in the adjacent neural retina (P vs A: E13.5: 109±40 vs 50±29, p=0.01; E14.5: 157±47 vs 79±29, p=0.01; N=6).

Conclusions : Our results indicate that the cell cycle regulator CyclinD2 is associated with the transition of RGC progenitors from the G1 to S phase, securing their mitotic exit in time to acquire ipsilateral fate through Zic2 expression. This process is perturbed in the albino mouse retina, and leads to a reduced Zic2+ RGC population and a diminished ipsilateral eye-to-brain projection.

This is a 2020 ARVO Annual Meeting abstract.

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