Quantification and image-derived phenotyping of retinal ganglion cell nuclei in the nee mouse model of congenital glaucoma

Heide, Carly J. van der; Meyer, Kacie J.; Hedberg-Buenz, Adam; Pellack, Danielle; Pomernackas, Nicholas; Mercer, Hannah E.; Anderson, Michael G.

doi:10.1016/j.exer.2021.108774

Cited by 2 publications

(1 citation statement)

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“… 72 , 73 We have previously found that 92.8% of RBPMS + cells co-label with BRN3A in retinas of normal C57BL/6J mice. 74 In sum, BRN3A appears to be present in a high percentage of RGCs, but any RGCs not detected by BRN3A immunolabeling could have confounded our analyses. Future iterations of this type of quantitative analysis of RGC somas may benefit from simultaneous application of an antibody targeting an RGC-specific marker coupled with retrograde labeling of the soma by way of the axon.…”

Section: Discussionmentioning

confidence: 80%

Biological Correlations and Confounders for Quantification of Retinal Ganglion Cells by Optical Coherence Tomography Based on Studies of Outbred Mice

Hedberg-Buenz

Meyer

Heide

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose Despite popularity of optical coherence tomography (OCT) in glaucoma studies, it's unclear how well OCT-derived metrics compare to traditional measures of retinal ganglion cell (RGC) abundance. Here, Diversity Outbred (J:DO) mice are used to directly compare ganglion cell complex (GCC) thickness measured by OCT to metrics of retinal anatomy measured ex vivo with retinal wholemounts and optic nerve histology. Methods J:DO mice (n = 48) underwent fundoscopic and OCT examinations, with automated segmentation of GCC thickness. RGC axons were quantified from para-phenylenediamine–stained optic nerve cross-sections and somas from BRN3A-immunolabeled retinal wholemounts, with total inner retinal cellularity assessed by TO-PRO and subsequent hematoxylin staining. Results J:DO tissues lacked overt disease. GCC thickness, RGC abundance, and total cell abundance varied broadly across individuals. GCC thickness correlated significantly to RGC somal density (r = 0.58) and axon number (r = 0.44), but not total cell density. Retinal area and nerve cross-sectional area varied widely. No metrics were significantly influenced by sex. In bilateral comparisons, GCC thickness ( r = 0.95), axon ( r = 0.72), and total cell density ( r = 0.47) correlated significantly within individuals. Conclusions Amongst outbred mice, OCT-derived measurements of GCC thickness correlate significantly to RGC somal and axon abundance. Factors limiting correlation are likely both biological and methodological, including differences in retinal area that distort sampling-based estimates of RGC abundance. Translational Relevance There are significant—but imperfect—correlations between GCC thickness and RGC abundance across genetic contexts in mice, highlighting valid uses and ongoing challenges for meaningful use of OCT-derived metrics.

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Section: Discussionmentioning

confidence: 80%