METHODS: We measured psychophysical contrast thresholds in one eye of 16 control subjects and 19 patients aged 67.8 ± 5.65 and 71.9 ± 7.15, respectively, (mean ± SD). Patients ranged in disease severity from suspects to severe glaucoma. We used the 17-region FDT-perimeter C20-threshold program and a custom 9-region test (R9) with similar visual field coverage. The R9 stimuli scaled their spatial frequencies with eccentricity and were modulated at lower temporal frequencies than C20 and thus did not display a clear spatial frequency-doubling (FD) appearance. Based on the overlapping areas of the stimuli, we transformed the C20 results to 9 measures for direct comparison with R9. We also compared mfVEP-based and psychophysical contrast thresholds in 26 younger (26.6 ± 7.3 y, mean ± SD) and 20 older normal control subjects (66.5 ± 7.3 y) control subjects using the R9 stimuli.
RESULTS: The best intraclass correlations between R9/C20 thresholds were for the central and outer regions: 0.82 ± 0.05 (mean ± SD, p ≤ 0.0001). The areas under receiver operator characteristic plots for C20 and R9 were as high as 0.99 ± 0.012 (mean ± SE). Canonical correlation analysis (CCA) showed significant correlation (r = 0.638, p = 0.029) with 1 dimension of the C20 and R9 data, suggesting that the lower and higher temporal frequency tests probed the same neural mechanism(s). Low signal quality made the contrast-threshold mfVEPs non-viable. The resulting mfVEP thresholds were limited by noise to artificially high contrasts, which unlike the psychophysical versions, were not correlated with age.
CONCLUSION: The lower temporal frequency R9 stimuli had similar diagnostic power to the FDT-C20 stimuli. CCA indicated the both stimuli drove similar neural mechanisms, possibly suggesting no advantage of FD stimuli for mfVEPs. Given that the contrast-threshold mfVEPs were non-viable, we used the present and published results to make recommendations for future mfVEP tests.
Methods: Light-induced damage to the retina was created by exposure of adult albino Sprague-Dawley rats to intense light for 24 hours. A single dose of Cx43MP, Cx43MP-NPs, or saline was injected intravitreally at 2 hours after onset of light damage. Fluorescein isothiocyanate (FITC)-labelled Cx43MP-NPs were intravitreally injected to confirm delivery into the retina. Electroretinogram (ERG) recordings were performed at 24 hours, 1 week, and 2 weeks post cessation of light damage. The retinal and choroidal layers were analyzed in vivo using optical coherence tomography (OCT) and immunohistochemistry was performed on harvested tissues using glial fibrillary acidic protein (GFAP), leukocyte common antigen (CD45), and Cx43 antibodies.
Results: FITC was visualized 30 minutes after injection in the ganglion cell layer and in the choroid. Cx43MP and Cx43MP-NP treatments improved a-wave and b-wave function of the ERG compared with saline-injected eyes at 1 week and 2 weeks post treatment, and prevented photoreceptor loss by 2 weeks post treatment. Inflammation was also reduced and this was in parallel with downregulation of Cx43 expression.
Conclusions: The slow release of Cx43MP incorporated into NPs is more effective at treating retinal injury than a single dose of native Cx43MP in solution by reducing inflammation and maintaining both retinal structure and function. This NP preparation has clinical relevance as it reduces possible ocular complications associated with repeated intravitreal injections.