Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission

Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina.

Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia

Daily OMR testing in young mice enhances visual function.

<p><b>(A)</b> Spatial frequency threshold measurements obtained daily from P16 to P23. Thresholds continued to increase until plateauing between P19 and P23. Control mice were measured on the final day of testing (P23). By P23, daily OMR testing resulted in 1.5x greater visual acuity thresholds than controls (Student’s t-test, p<0.001). <b>(B)</b> On the final day of testing, contrast sensitivity was 5x increased in OMR-treated mice (Student’s t-test, p = 0.002). Data are represented as mean ± SEM. **p<0.01, ***p<0.001, a.u. = arbitrary units.</p

Improvements in visual function with daily OMR stimulation dependent on BDNF signaling.

<p><b>(A)</b> Spatial frequency thresholds measured daily from P16 to P23 were significantly reduced in mice receiving the TrkB antagonist, ANA-12, compared to vehicle-injected mice. By the second day of testing, OMR+Vehicle mice had significantly greater spatial frequency thresholds than the OMR+ANA-12 mice (Two-way repeated measures ANOVA F(7,117) = 14.95, *p<0.05 on P17) with this difference continuing until P23 (***p<0.001 on P18-P23). Control mice were measured on the final day of testing. At P23, daily OMR testing resulted in <b>(B)</b> 1.5x greater spatial frequency thresholds and <b>(C)</b> 3.9x greater contrast sensitivity in OMR+Vehicle as compared to Control+Vehicle mice (One-way ANOVA F(3,19) = 33.7, p<0.001). These enhancements were diminished in OMR+ANA-12 mice, which had only 1.2x greater spatial frequency thresholds (Kruskal-Wallis one-way ANOVA on ranks, H = 18.9, p<0.01) and contrast sensitivity indistinguishable from the Control+Vehicle mice. Data are represented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, a.u. = arbitrary units.</p

Minimizing the Negative Externality from Sachet Water Consumption in Nigeria

Over the years, there has been a consistent increase in the production and use of plastic and sachet packaged products in Nigeria which results in a proportional increase in plastic and Nylon waste pollution in the environment. An earlier survey show that the introduction of sachet water in the country some years ago worsened the situation as it contributes to more than 60% of the sachet pollution. This study therefore tried to find out an efficient and sustainable means of collecting the used sachet water bags to minimize its negative external impact on the environment. It was carried out using primary data collected through direct interview from a sample of 1500 individual in some selected states in the Country. The data was analysed using descriptive statistics and Log-log regression model. The results of the analysis show that PPP method can be effective in managing the menace. Majority of the sampled individuals are of the opinion that a 100% PPP levy will be a sufficient motivation for sachet water users to return their used sachet water bags to the appropriate collection sites in return for their levy or for the trash pickers to collect them for an equivalent payment. Keywords: Sachet water, biodegradable, Pollution, Externality, Plastic Polluter Pay (PPP

Electrophysiological results show selective improvement in scotopic inner retinal function.

<p><b>(A)</b> Representative dark-adapted ERG waveforms across flash stimuli illustrating that daily OMR stimulation does not improve photoreceptor and bipolar cell function—indicated by <b>(B)</b> dark-adapted a- and b-wave amplitudes across increasing flash stimuli, respectively. ERG measurements are indicated in the top waveform in <b>(A)</b>: a-wave amplitude is the difference between points 1 and 2, and b-wave amplitude is the difference between points 2 and 3. <b>(C)</b> Representative dark-adapted ERG OP2 waveforms in response to increasing flash stimuli with an arrowhead that designates a significantly faster OP2 in OMR-treated mice in response to -2.5 log cd/sm² flash stimuli (Two-way repeated measures ANOVA F(4, 70), p = 0.004, Holm-Sidak multiple comparison at 2.5 log∙cd∙s/m², *p<0.05). This is quantified in <b>(D)</b>, and suggests improvements in rod-driven inner retinal processing in OMR-treated mice. <b>(E)</b> Representative PERG waveforms in response to patterned stimuli show no significant differences between OMR-treated and control mice in either <b>(F)</b> amplitude or latency, suggesting no significant improvements in retinal ganglion cell function with OMR treatment. <b>(G)</b> Visual cortex function was also not significantly improved with OMR stimulation, as seen in representative VEP waveforms in response to 1.4 log cd s/m² stimuli. <b>(H)</b> VEP amplitude and implicit time were not statistically different between the control and OMR-treated mice. Data are represented as mean ± SEM.</p