The Effect of Ametropia on Glaucomatous Visual Field Loss.

Myopia has been discussed as a risk factor for glaucoma. In this study, we characterized the relationship between ametropia and patterns of visual field (VF) loss in glaucoma. Reliable automated VFs (SITA Standard 24-2) of 120,019 eyes from 70,495 patients were selected from five academic institutions. The pattern deviation (PD) at each VF location was modeled by linear regression with ametropia (defined as spherical equivalent (SE) starting from extreme high myopia), mean deviation (MD), and their interaction (SE × MD) as regressors. Myopia was associated with decreased PD at the paracentral and temporal VF locations, whereas hyperopia was associated with decreased PD at the Bjerrum and nasal step locations. The severity of VF loss modulated the effect of ametropia: with decreasing MD and SE, paracentral/nasal step regions became more depressed and Bjerrum/temporal regions less depressed. Increasing degree of myopia was positively correlated with VF depression at four central points, and the correlation became stronger with increasing VF loss severity. With worsening VF loss, myopes have increased VF depressions at the paracentral and nasal step regions, while hyperopes have increased depressions at the Bjerrum and temporal locations. Clinicians should be aware of these effects of ametropia when interpreting VF loss.

Rational design of silicon structures for optically controlled multiscale biointerfaces.

Silicon-based materials have been widely used. However, remotely controlled and interconnect-free silicon configurations have been rarely explored, because of limited fundamental understanding of the complex physicochemical processes that occur at interfaces between silicon and biological materials. Here, we describe rational design principles, guided by biology, for establishing intracellular, intercellular and extracellular silicon-based interfaces, where the silicon and the biological targets have matched properties. We focused on light-induced processes at these interfaces, and developed a set of matrices to quantify and differentiate the capacitive, Faradaic and thermal outputs from about 30 different silicon materials in saline. We show that these interfaces are useful for the light-controlled non-genetic modulation of intracellular calcium dynamics, of cytoskeletal structures and transport, of cellular excitability, of neurotransmitter release from brain slices, and of brain activity in vivo.

Heterogeneous silicon mesostructures for lipid-supported bioelectric interfaces.

Silicon-based materials have widespread application as biophysical tools and biomedical devices. Here we introduce a biocompatible and degradable mesostructured form of silicon with multi-scale structural and chemical heterogeneities. The material was synthesized using mesoporous silica as a template through a chemical vapour deposition process. It has an amorphous atomic structure, an ordered nanowire-based framework and random submicrometre voids, and shows an average Young's modulus that is 2-3 orders of magnitude smaller than that of single-crystalline silicon. In addition, we used the heterogeneous silicon mesostructures to design a lipid-bilayer-supported bioelectric interface that is remotely controlled and temporally transient, and that permits non-genetic and subcellular optical modulation of the electrophysiology dynamics in single dorsal root ganglia neurons. Our findings suggest that the biomimetic expansion of silicon into heterogeneous and deformable forms can open up opportunities in extracellular biomaterial or bioelectric systems.

Efficacy of electrical stimulation of retinal ganglion cells with temporal patterns resembling light-evoked spike trains.

People with degenerative retinal diseases such as retinitis pigmentosa lose most of their photoreceptors but retain a significant proportion (~30%) of their retinal ganglion cells (RGCs). Microelectronic retinal prostheses aim to bypass the lost photoreceptors and restore vision by directly stimulating the surviving RGCs. Here we investigate the extent to which electrical stimulation of RGCs can evoke neural spike trains with statistics resembling those of normal visually-evoked responses. Whole-cell patch clamp recordings were made from individual cat RGCs in vitro. We first recorded the responses of each cell to short sequences of visual stimulation. These responses were converted to trains of electrical stimulation that we then presented to the same cell via an epiretinal stimulating electrode. We then quantified the efficacy of the electrical stimuli and the latency of the evoked spikes. In all cases, spikes were evoked with sub-millisecond latency (0.55 ms, median, ON cells, n = 8; 0.75 ms, median, OFF cells, n = 6) and efficacy ranged from 0.4-1.0 (0.79, median, ON cells; 0.97, median, OFF cells). These data demonstrate that meaningful spike trains, resembling normal responses of RGCs to visual stimulation, can be reliably evoked by epiretinal prostheses.

Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis.

Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.

Epiretinal electrical stimulation and the inner limiting membrane in rat retina.

In this paper we aim to quantify the effect of the inner limiting membrane (ILM) of the retina on the thresholds for epiretinal electrical stimulation of retinal ganglion cells by a microelectronic retinal prosthesis. A pair of bipolar stimulating electrodes was placed either above (on the epiretinal surface) or below the ILM while we made whole-cell patch-clamp recordings from retinal ganglion cells in an isolated rat retinal whole-mount preparation. Across our cell population we found no significant difference in the median threshold stimulus amplitudes when the stimulating electrodes were placed below as opposed to above the ILM (p = 0.08). However, threshold stimulus amplitudes did tend to be lower when the stimulating electrodes were placed below the ILM (30 µA vs 56 µA).