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Clinical Trial
. 2017 Jun 1;140(6):1757-1767.
doi: 10.1093/brain/awx088.

Real-time imaging of single neuronal cell apoptosis in patients with glaucoma

Maria F Cordeiro  1   2   3 , Eduardo M Normando  2   3 , M Jorge Cardoso  4 , Serge Miodragovic  2 , Seham Jeylani  2 , Benjamin M Davis  1 , Li Guo  1 , Sebastien Ourselin  4 , Roger A'Hern  5 , Philip A Bloom  2   3
Affiliations
Clinical Trial

Real-time imaging of single neuronal cell apoptosis in patients with glaucoma

Maria F Cordeiro et al. Brain. .
No abstract available

Keywords: apoptosis; glaucoma; real-time visualization; retinal imaging.

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Figures

Figure 1
Figure 1
DARC counts are increased in affected glaucoma patients compared to healthy controls. ANX776 injections revealed single neuronal cell apoptosis in the retina of study subjects. Representative retinal images are shown from glaucoma patients following intravenous injections of 0.4 (A and B), 0.2 (C and D) and 0.5 (E and F) mg ANX776 at 240 minutes. Panels show unmarked (A, C and E) and marked (B, D and F) ANX776-positive spots with yellow rings highlighting individual spots. DARC counts were defined as new, unique individual ANX776-labelled spots, at their first appearance in the retina. Analysis of DARC counts in glaucoma and healthy controls for each ANX776 dosing cohort showed that at each dose, the number of DARC spot counts was consistently higher in glaucoma patients compared to healthy controls, and this reached significance at the 0.4 mg (P < 0.005) dose (G). The spread of the individual data points is shown in Tukey’s box plots (G). Horizontal lines indicate medians and interquartile ranges with the continuous line across doses showing the means. Asterisks indicate the level of significance by Bonferroni multiple comparison test between groups (P < 0.01) with two-way ANOVA across the doses showing a significant effect of glaucoma status (P = 0.0033) and time point (P = 0.0011). Multivariable analysis indicated that the total DARC count across 6 h was 2.37-fold higher in patients with glaucoma (95% CI: 1.4–4.03, P = 0.003) at any dose. Different fluorescent intensity profiles were seen for individual labelled spots (H–P). Low (I, K, M and O) and high (J, L, N and P) magnification (scale bars indicated) retinal images at different time points are shown from the same patient as in A at baseline (I and J, 0 min), 60 (K and L), 120 (M and N) and 240 (O and P) min. Marked, colour-coded spots are shown in adjacent panels (J, L, N and P) with fluorescent intensity profiles illustrated in H, identified by corresponding coloured lines.
Figure 2
Figure 2
DARC counts are significantly increased in glaucoma patients with increasing rates of progression compared to healthy controls. The rate of progression (RoP) was calculated for all parameters at baseline and follow-up for all glaucoma patients, where an increasing rate of progression was computed from the difference between follow-up and baseline significant (P < 0.05) negative slopes. The DARC count was significantly increased in glaucoma patients with increasing rate of progression in any one parameter, compared to healthy controls, as shown in Tukey’s box plots illustrating individual data points in glaucoma patients with and without increasing rate of progression compared to healthy controls. Asterisks indicate level of significance by Dunn’s multiple comparison test between groups (P < 0.05) with Kruskal Wallis one-way ANOVA showing statistical significance across three groups (P = 0.0448). Horizontal lines indicate medians and interquartile ranges with ×’ symbol showing the means, and all individual data points indicated. See also Table 3.
Figure 3
Figure 3
ANX776 pharmacokinetics and pharmacodynamics. The mean serum concentration of ANX776 over time after a single intravenous administration of five different dose levels is shown with standard error bars in healthy and glaucoma cohorts. See also Table 5.
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