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Yousef Cruz-Inigo, Manoj K Mishra, Rangaramanujam Kannan, William C Gordon, Nicos Petasis, Nicolas G Bazan, Raymond Iezzi; Neuroprotective Bioactivity of NPD1 and Dendrimer-NPD1 in the S334-ter-5 model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5759.
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© ARVO (1962-2015); The Authors (2016-present)
To test the neuroprotective bioactivity of neuroprotectin-D1 (NPD1) with and without conjugation to dendrimer nanoparticles (D-NPD1) in S334-ter line-5 rats.
Thirty-eight S334-ter-5 rats aged 22 days were divided into five groups; low-dose NPD1 (0.1μg ), high-dose NPD1 (1.0 μg), low-dose D-NPD1 (0.1μg), high-dose D-NPD1 (1.0 μg), and non-conjugated free-dendrimer (1.0 μg). Right eyes were injected, while fellow left eyes served as non-injected controls. Baseline ERGs were compared to 30-day post-injection measurements when outer nuclear layer (ONL) thickness was also measured, histologically. After non-parametric testing, the paired t-test was performed.
High NPD1, low NPD1 and low D-NPD1 protected ERG amplitudes (p < 0.05) and ONL thickness (p < 0.001) over the thirty day study period. Control eyes demonstrated a nearly 60% decrease in ERG amplitudes, while in high-dose NPD1 eyes, ERG b-wave amplitudes decreased 32.9% ± 4.8 (scotopic) and -1.6% ± 6.2 (photopic); in low NPD1, decreases were 37.2% ± 6.5, and 10.5% ± 4.2 (scotopic and photopic); and in the low D-NPD1 group amplitudes decreased, 41.1% ± 4.4 and 29.9% ± 7.6 (scotopic and photopic). Non-conjugated dendrimer treated eyes decreased 59.8%% ± 13.3. ONL thickness measurements in high NPD1, right 21.1 ± 0.41 μM vs left 17.6 ± 0.36 μM, low NPD1 right 21.5 ± 0.40 μM vs left 16.6 ± 0.37 μM, low D-NPD1 right 32.7 ± 0.43 μM vs left 19.8 ± 0.41 μM and free- dendrimer, right 17.2 ± 0.40 μM vs left 18.6 ± 0.37 μM. The high NPD1, low NPD1 and low D-NPD1 groups demonstrated significantly greater ONL thickness as compared to the left un-injected control (p < 0.001) and unconjugated dendrimer control (p < 0.001). Only fellow (untreated) eyes of the high D-NPD1 group showed significant preservation for both scotopic and photopic systems, p< 0.05. In this group, the photopic b-wave decreased 41.8% ± 5.0 in treated vs 26.0% ± 2.7 in fellow, untreated eyes p = 0.022. Further, ONL thickness in this group was significantly greater in un-injected eyes (22.8 ± 0.32 μM) as compared to right eyes (17.8 ±0.37 μM, p< 0.001) and free-dendrimer injected eyes (17.2 ± 0.40 μM, p< 0.001).
In the S334-ter line 5 rat model, NPD1 and low D-NPD1 showed significant ERG and ONL protection in treated eyes as comparison to fellow eyes. In contrast, high D-NPD1 showed significant crossover neuroprotection in the fellow (untreated) eyes.
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