Aqueous angiography in pre-glaucomatous and glaucomatous ADAMTS10-mutant canine eyes: A pilot study.

OBJECTIVE: To evaluate intravenous scleral and intracameral aqueous angiography in normotensive (n = 4) and hypertensive glaucomatous (n = 6) ADAMTS10-mutant canine eyes. ANIMALS STUDIED: Ten ADAMTS10-mutant dogs were used in this study. PROCEDURES: Dogs were sedated and one eye from each dog underwent scleral angiography following intravenous injection of 0.25% indocyanine green (ICG). After a 24-h recovery period, the same eye underwent aqueous angiography via intracameral administration of ICG. Imaging of identical scleral sectors from the same eye was performed using a Heidelberg Spectralis® Confocal Scanning Laser Ophthalmoscope. Intrascleral vessel depth and lumen diameters were measured using Heidelberg Spectralis® optical coherence tomography and computer software. RESULTS: Scleral angiography permitted visualization of vascular components associated with conventional aqueous humor outflow pathways with an average time from injection to fluorescence of 35.8 ± 10.6 s (mean ± SD). Two normotensive eyes (2/10;20%) demonstrated turbulent dye movement, while 4 hypertensive eyes (4/10;40%) exhibited laminar flow. Aqueous angiography demonstrated dye fluorescence within the post-trabecular conventional aqueous humor outflow pathways in all 10 eyes at 34.3 ± 11.0 s post-injection. Sectoral and dynamic outflow patterns were observed primarily within the superotemporal sector in nine eyes (9/10; 90%). Seven eyes (7/10; 70%) demonstrated pulsatile dye movement and five eyes (5/10; 50%) exhibited laminar flow. The degree of laminar movement of dye was greatest in hypertensive eyes. Vessel lumen diameters measured 133.85 ± 28.36 µm and 161.18 ± 6.02 µm in hypertensive and normotensive eyes, respectively. CONCLUSIONS: Aqueous angiography allowed for visualization of fluorescent dye in the superotemporal sclera. Laminar flow and smaller lumen vessels were observed mainly in hypertensive eyes.

Dual Immunostaining With SOX10 and AE1/AE3 to Confirm Perineural Invasion on Mohs Sections

Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs. J Drugs Dermatol. 2019;18(3):262-264.

Imidazolium-Catalyzed Synthesis of an Imidazolium Catalyst.

The chemistry of imidazolium-catalyzed imidazolium synthesis was studied as part of an effort to develop a plausible prebiotic synthesis of a small catalytic molecule capable of catalyzing its own synthesis. Specifically, we investigated the one-pot 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) catalyzed synthesis of 1,3-dibutyl-4,5-difuryl-imidazolium acetate (DBDFIM-Ac) from furfural, n-butylamine, formaldehyde, and acetic acid at 80 °C. Liu et al. (2012) had previously demonstrated the first reaction of the synthetic process, the EMIM-Ac catalyzed benzoin condensation of furfural that yields furoin. Our early studies established the second reaction of the synthetic process, the multicomponent reaction of furoin, n-butylamine, formaldehyde, and acetic acid that yields the imidazolium salt, DBDFIM-Ac. Studies of the complete two-reaction process that uses furfural for the synthesis of DBDFIM-Ac showed that the highest yield of DBDFIM-Ac was obtained when the mole ratio of n-butylamine, formaldehyde, and acetic acid relative to furfural was respectively (0.5:0.25:0.25:1.0-furfural), or one-half of the stoichiometric ratio (1.0:0.5:0.5:1.0-furfural). A time course study of the process showed transient formation of furoin, the obligatory reaction intermediate. DBDFIM-Ac and the imidazolium side product, 1,3-dibutyl-4,5-trifuryl-imidazolium acetate (DBTFIM-Ac), were stable under the reaction conditions. Imidazolium products (DBDFIM and DBTFIM) and the furoin intermediate were not formed in control reactions (80 °C, 24 h) in which EMIM catalyst was either absent or replaced with an equal volume of acetonitrile or DMF. The imidazolium product, DBDFIM-Ac, was shown to catalyze the synthesis of structurally similar 1,3-dipentyl-4,5-difuryl-imidazolium acetate (DPDFIM-Ac) from furfural, n-pentylamine, formaldehyde, and acetic acid at 80 °C.

Synthesis of ß-Peptide Standards for Use in Model Prebiotic Reactions.

A one-pot method was developed for the preparation of a series of ß-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of ß-alanine methyl ester, yielding ß-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of ß-alanine peptide methyl ester oligomers, producing a series of ß-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of ß-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of ß-peptide standards for investigating differences between α- and ß-peptides in the context of prebiotic chemistry.

Imidazolium Catalysts Formed by an Iterative Synthetic Process as a Model System for Chemical Evolution.

Processes exhibiting diversity and selection would have been necessary to promote chemical evolution on early Earth. In this work, a model process was developed using non-kinetic selection to synthesize and isolate small molecule imidazolium catalysts. These catalysts were purified by affinity chromatography and recycled back into the process, forming a product feedback loop. In dimethylformamide, the catalysts activated the coupling of formaldehyde to short chain sugars. This sugar mixture was reacted with aniline, acetic acid, and paraformaldehyde to generate new catalysts. Thus chemical diversity was produced through non-selective, multi-component synthesis. Applying sequential dilution-reaction-purification cycles it was demonstrated that this process can function independently of starting catalyst. Over three process cycles, the initiator catalyst is effectively diluted out as a new catalyst population emerges to take its place. This system offers an alternative viewpoint for chemical evolution via the generation of small molecule organocatalysts.

Serum myostatin as a candidate disease severity and progression biomarker of spinal muscular atrophy.

The identification of biomarkers for spinal muscular atrophy is crucial for predicting disease progression, severity, and response to new disease-modifying therapies. This study aimed to investigate the role of serum levels of myostatin and follistatin as biomarkers for spinal muscular atrophy, considering muscle atrophy secondary to denervation as the main clinical manifestation of the disease. The study evaluated the differential gene expression of myostatin and follistatin in a lesional model of gastrocnemius denervation in mice, as well as in a meta-analysis of three datasets in transgenic mice models of spinal muscular atrophy, and in two studies involving humans with spinal muscular atrophy. Subsequently, a case-control study involving 27 spinal muscular atrophy patients and 27 controls was conducted, followed by a 12-month cohort study with 25 spinal muscular atrophy cases. Serum levels of myostatin and follistatin were analysed using enzyme-linked immunosorbent assay at a single centre in southern Brazil. Skeletal muscle gene expression of myostatin decreased and of follistatin increased following lesional muscle denervation in mice, consistent with findings in the spinal muscular atrophy transgenic mice meta-analysis and in the iliopsoas muscle of five patients with spinal muscular atrophy type 1. Median serum myostatin levels were significantly lower in spinal muscular atrophy patients (98 pg/mL; 5-157) compared to controls (412 pg/mL; 299-730) (P < 0.001). Lower myostatin levels were associated with greater disease severity based on clinician-rated outcomes (Rho = 0.493-0.812; P < 0.05). After 12 months, there was a further reduction in myostatin levels among spinal muscular atrophy cases (P = 0.021). Follistatin levels did not differ between cases and controls, and no significant changes were observed over time. The follistatin:myostatin ratio was significantly increased in spinal muscular atrophy subjects and inversely correlated with motor severity. Serum myostatin levels show promise as a novel biomarker for evaluating the severity and progression of spinal muscular atrophy. The decrease in myostatin levels and the subsequent favourable environment for muscle growth may be attributed to denervation caused by motor neuron dysfunction.

Autocrine and paracrine interactions and neuroprotection in glaucoma.

Retinal ganglion cells represent the output neurons of the retina. They are responsible for integrating electrical signals that originate with the photoreceptors and, via their axons that comprise the optic nerve, transmit that information to higher visual centers of the brain. The retinal ganglion cells reside on the inner surface of the retina and their axons course across the inner surface to exit at the back of the eye through a region known as the optic nerve head. Within this region, initiation of the degenerative processes associated with glaucoma are thought to occur, leading to degeneration of not only the optic nerve but also the retinal ganglion cells themselves. Studies aimed at understanding the mechanisms behind glaucoma have identified diverse cellular components and molecular events that occur in response to nerve injury. The challenge to date has been to identify and promote pro-survival events while suppressing those that support further degradation and loss of vision. Complicating this process is the fact that the cells and molecules involved can play multiple roles. An understanding of the players and their complex relationships is central to the development of a successful treatment strategy.

A fully transparent, flexible PEDOT:PSS-ITO-Ag-ITO based microelectrode array for ECoG recording.

Integrative neural interfaces combining neurophysiology and optogenetics with neural imaging provide numerous opportunities for neuroscientists to study the structure and function of neural circuits in the brain. Such a comprehensive interface demands miniature electrode arrays with high transparency, mechanical flexibility, electrical conductivity, and biocompatibility. Conventional transparent microelectrodes made of a single material, such as indium tin oxide (ITO), ultrathin metals, graphene and poly-(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS), hardly possess the desired combination of those properties. Herein, ultra-flexible, highly conductive and fully transparent microscale electrocorticogram (µECoG) electrode arrays made of a PEDOT:PSS-ITO-Ag-ITO assembly are constructed on thin parylene C films. The PEDOT:PSS-ITO-Ag-ITO assembly achieves a maximum ∼14% enhancement in light transmission over a broad spectrum (350-650 nm), a significant reduction in electrochemical impedance by 91.25%, and an increase in charge storage capacitance by 1229.78 µC cm-2. Peeling, bending, and Young's modulus tests verify the enhanced mechanical flexibility and robustness of the multilayer assembly. The µECoG electrodes enable electrical recordings with high signal-to-noise ratios (SNRs) (∼35-36 dB) under different color photostimulations, suggesting that the electrodes are resilient to photon-induced artifacts. In vivo animal experiments confirm that our array can successfully record light-evoked ECoG oscillations from the primary visual cortex (V1) of an anesthetized rat.

Sugar-driven prebiotic synthesis of ammonia from nitrite.

Reaction of 3-5 carbon sugars, glycolaldehyde, and alpha-ketoaldehydes with nitrite under mild anaerobic aqueous conditions yielded ammonia, an essential substrate for the synthesis of nitrogen-containing molecules during abiogenesis. Under the same conditions, ammonia synthesis was not driven by formaldehyde, glyoxylate, 2-deoxyribose, and glucose, a result indicating that the reduction process requires an organic reductant containing either an accessible alpha-hydroxycarbonyl group or an alpha-dicarbonyl group. Small amounts of aqueous Fe(+3) catalyzed the sugar-driven synthesis of ammonia. The glyceraldehyde concentration dependence of ammonia synthesis, and control studies of ammonia's reaction with glyceraldehyde, indicated that ammonia formation is accompanied by incorporation of part of the synthesized ammonia into sugar-derived organic products. The ability of sugars to drive the synthesis of ammonia is considered important to abiogenesis because it provides a way to generate photochemically unstable ammonia at sites of sugar-based origin-of-life processes from nitrite, a plausible prebiotic nitrogen species.

Stereoselective syntheses of pentose sugars under realistic prebiotic conditions.

Glycolaldehyde and DL-glyceraldehyde reacted in a water-buffered solution under mildly acidic conditions and in the presence of chiral dipeptide catalysts produced pentose sugars whose configuration is affected by the chirality of the catalyst. The chiral effect was found to vary between catalysts and to be largest for di-valine. Lyxose, arabinose, ribose and xylose are formed in different amounts, whose relative proportions do not change significantly with the varying of conditions. With LL-peptide catalysts, ribose was the only pentose sugar to have a significant D-enantiomeric excess (ee) (

A mm-Sized Free-Floating Wireless Implantable Opto-Electro Stimulation Device.

Towards a distributed neural interface, consisting of multiple miniaturized implants, for interfacing with large-scale neuronal ensembles over large brain areas, this paper presents a mm-sized free-floating wirelessly-powered implantable opto-electro stimulation (FF-WIOS2) device equipped with 16-ch optical and 4-ch electrical stimulation for reconfigurable neuromodulation. The FF-WIOS2 is wirelessly powered and controlled through a 3-coil inductive link at 60 MHz. The FF-WIOS2 receives stimulation parameters via on-off keying (OOK) while sending its rectified voltage information to an external headstage for closed-loop power control (CLPC) via load-shift-keying (LSK). The FF-WIOS2 system-on-chip (SoC), fabricated in a 0.35-µm standard CMOS process, employs switched-capacitor-based stimulation (SCS) architecture to provide large instantaneous current needed for surpassing the optical stimulation threshold. The SCS charger charges an off-chip capacitor up to 5 V at 37% efficiency. At the onset of stimulation, the capacitor delivers charge with peak current in 1.7-12 mA range to a micro-LED (µLED) array for optical stimulation or 100-700 µA range to a micro-electrode array (MEA) for biphasic electrical stimulation. Active and passive charge balancing circuits are activated in electrical stimulation mode to ensure stimulation safety. In vivo experiments conducted on three anesthetized rats verified the efficacy of the two stimulation mechanisms. The proposed FF-WIOS2 is potentially a reconfigurable tool for performing untethered neuromodulation.

Wireless, passive strain sensor in a doughnut-shaped contact lens for continuous non-invasive self-monitoring of intraocular pressure.

After cataract, glaucoma is the second leading cause of blindness worldwide and real-time monitoring of intraocular pressure (IOP) is of great demand. We present a wireless, passive sensor sitting inside a customized, planar and circular doughnut-shaped contact lens capable of continuous monitoring of the change in the curvature of cornea caused by IOP fluctuations. The sensor consists of a constant capacitor and a variable inductor in the form of a stretchable, closed-loop, serpentine wire that serves as both the sensor and the antenna. Results show a pressure responsivity of 523 kHz per 1% axial strain on a pressurized polydimethylsiloxane membrane and 35.1 kHz per 1 mmHg change in the IOP of a canine eye. The sensor is tested for stability and shows unvaried characteristics after repeated cycles and parasitic movements. Predictable influences of temperature and humidity on the sensor response are also verified experimentally, which can be canceled out using real-time calibration with temperature and humidity sensors to integrate with a reader device. The design reported here has numerous advantages, such as design simplicity, component reliability, high responsivity, and low cost, thereby opening up potential opportunities for the translation of this non-invasive, continuous IOP monitoring technique into clinical applications.

Aqueous Angiography in Normal Canine Eyes.

Purpose: To conduct aqueous angiography (AA) using a clinically applicable technique in normal dogs and to compare findings to intravenous scleral angiography (SA). Methods: We examined 10 canine cadaver eyes and 12 eyes from live normal dogs. A gravity-fed trocar system delivered 2% sodium fluorescein and 0.25% indocyanine green (ICG) intracamerally (IC) in cadaver eyes. In vivo AA was subsequently performed in one eye of each of the 12 dogs via IC bolus of ICG under sedation. The same 12 dogs received SA via intravenous ICG (mean ± SD) 10.7 ± 3.3 days later. Identical scleral sectors were imaged using a Spectralis confocal scanning laser ophthalmoscope. Results: The gravity-fed trocar system permitted visualization of the conventional aqueous humor outflow (CAHO) pathways in cadaver eyes, but not in vivo. Fluorescence was observed superonasally in four of the 10 cadaver eyes within 24.0 ± 3.6 seconds. A single IC bolus of ICG showed CAHO pathways in vivo, demonstrating sectoral outflow patterns in the superotemporal sclera in 10 of the 12 eyes within 35.0 ± 4.3 seconds; four of the 12 eyes exhibited pulsatile aqueous movement. SA exhibited fluorescence patterns comparable to AA with weak pulsatile aqueous humor outflow. Conclusions: Angiography (AA or SA) in dogs permits visualization of the CAHO pathway and its vascular components in vivo. AA may be a more useful modality to assess aqueous humor outflow. Translational Relevance: Intracameral AA has potential utility for evaluating CAHO in vivo in dogs, an important animal model species.

A Trimodal Wireless Implantable Neural Interface System-on-Chip.

A wireless and battery-less trimodal neural interface system-on-chip (SoC), capable of 16-ch neural recording, 8-ch electrical stimulation, and 16-ch optical stimulation, all integrated on a 5 ×  3 mm2 chip fabricated in 0.35-µm standard CMOS process. The trimodal SoC is designed to be inductively powered and communicated. The downlink data telemetry utilizes on-off keying pulse-position modulation (OOK-PPM) of the power carrier to deliver configuration and control commands at 50 kbps. The analog front-end (AFE) provides adjustable mid-band gain of 55-70 dB, low/high cut-off frequencies of 1-100 Hz/10 kHz, and input-referred noise of 3.46 µVrms within 1 Hz-50 kHz band. AFE outputs of every two-channel are digitized by a 50 kS/s 10-bit SAR-ADC, and multiplexed together to form a 6.78 Mbps data stream to be sent out by OOK modulating a 434 MHz RF carrier through a power amplifier (PA) and 6 cm monopole antenna, which form the uplink data telemetry. Optical stimulation has a switched-capacitor based stimulation (SCS) architecture, which can sequentially charge four storage capacitor banks up to 4 V and discharge them in selected µLEDs at instantaneous current levels of up to 24.8 mA on demand. Electrical stimulation is supported by four independently driven stimulating sites at 5-bit controllable current levels in ±(25-775) µA range, while active/passive charge balancing circuits ensure safety. In vivo testing was conducted on four anesthetized rats to verify the functionality of the trimodal SoC.

Synthesis and base-pairing properties of pyrazine nucleic acids.

The diversity of backbone modifications in the study of primitive informational polymers is partly limited by the plausible formation of their prebiotic starting components. In this paper, we synthesize pyrazine nucleic acid, an acyclic polymer, with the nucleoside derivable from a prebiotic one-pot synthesis containing alanine amide and D-ribose. Pyrazine nucleic acid (PzNA) which has a backbone structurally similar to glycerol nucleic acid (GNA), contain pyrazine derived nucleosides as informational elements that may exhibit base pairing properties similar to the pyrimidines present in RNA.[1] We found that insertion of pyrazinone nucleotides into DNA oligonucleotide sequences is not well-tolerated, and that homogenous sequences of PzNA are unable to form duplexes with RNA or DNA. Reasons for our results may be attributed to the pyrazine-2-one moiety, which is purposed to be a thymine analog, but has a lower pKa (pKa ∼ 8.5) than thymine and uracil. Additionally, we discovered an "apparent" regioselective protection of pyrazine-2-one derivatives in the presence of a secondary hydroxyl group that proved crucial in the preparation of the pyrazine-2-one phosphoramidite. The regioselectivity observed is proposed to be of general interest in the context of heterocyclic chemistry. In the larger context of origins of life studies, it points to the importance of keto-enol preferences of the canonical nucleobases versus pyrazine heterocycles in functioning as recognition elements.

Flexible, diamond-based microelectrodes fabricated using the diamond growth side for neural sensing.

Diamond possesses many favorable properties for biochemical sensors, including biocompatibility, chemical inertness, resistance to biofouling, an extremely wide potential window, and low double-layer capacitance. The hardness of diamond, however, has hindered its applications in neural implants due to the mechanical property mismatch between diamond and soft nervous tissues. Here, we present a flexible, diamond-based microelectrode probe consisting of multichannel boron-doped polycrystalline diamond (BDD) microelectrodes on a soft Parylene C substrate. We developed and optimized a wafer-scale fabrication approach that allows the use of the growth side of the BDD thin film as the sensing surface. Compared to the nucleation surface, the BDD growth side exhibited a rougher morphology, a higher sp 3 content, a wider water potential window, and a lower background current. The dopamine (DA) sensing capability of the BDD growth surface electrodes was validated in a 1.0 mM DA solution, which shows better sensitivity and stability than the BDD nucleation surface electrodes. The results of these comparative studies suggest that using the BDD growth surface for making implantable microelectrodes has significant advantages in terms of the sensitivity, selectivity, and stability of a neural implant. Furthermore, we validated the functionality of the BDD growth side electrodes for neural recordings both in vitro and in vivo. The biocompatibility of the microcrystalline diamond film was also assessed in vitro using rat cortical neuron cultures.

Acute Effects of Sport-Related Concussion on Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase L1, Total Tau, and Neurofilament Light Measured by a Multiplex Assay.

We prospectively evaluated serum concentrations of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau (T-Tau), and neurofilament light (NF-L) from collegiate athletes at baseline and acutely after sport-related concussion (SRC) using the Quanterix Neurology 4Plex "B" (N4PB) multiplex assay. Uninjured controls were matched on age, sex, race, sport, and concussion history. Clinical outcomes included acute symptom severity, balance, rapid automated naming, computerized cognitive testing, and recovery duration. Baseline (n = 110; median [interquartile range] age = 19 [18-20] years, 54% male, 61% white/Caucasian) and post-SRC (n = 36; median [interquartile range] age = 19 [18-20] years, 50% male, 61% white/Caucasian) blood samples were analyzed. We observed post-SRC elevations from baseline for GFAP (p = 0.001, d = 1.7), T-Tau (p = 0.004, d = 1.3), and NF-L (p = 0.010, d = 1.1). GFAP (area under the curve [AUC] = 0.958, 95% confidence interval [CI] 0.927-0.989, p < 0.001) and NF-L (AUC = 0.904, 95% CI 0.851-0.957, p < 0.001) accurately discriminated SRC from control cases. There were no associations between biomarker concentrations and clinical measurements post-SRC or recovery duration. These findings suggest that, using the multiplex assay, GFAP, T-Tau, and NF-L elevate from baseline acutely after SRC, and both GFAP and NF-L excellently distinguished concussed from control cases. Serum biomarker changes do not necessarily correspond with clinical measurements or recovery duration.

Inductively coupled, mm-sized, single channel optical neuro-stimulator with intensity enhancer.

We introduce a single channel neuro-stimulator consisting of a reflector-coupled microscale light emitting diode (µLED) with an integrated mm-sized wireless receiver (Rx) coil for free-floating, battery-free, untethered optogenetics neuromodulation. The system utilizes a two-coil inductive link to deliver instantaneous power at a low operating frequency (<100 MHz) for continuous optical stimulation with minimized invasiveness and tissue exposure to electromagnetic radiation. Coupling a microscale reflector to the µLED provides significant light intensity enhancement compared to a bare µLED. Our activated stimulators have an operational temperature increase of <1 °C, well below the safety limit of biomedical implants. In vivo experiment and histological analysis verify the efficacy of wireless optical stimulation in the primary visual cortex of rats, using c-Fos biomarker as a reporter of light-evoked neuronal activity.

A mm-Sized Free-Floating Wirelessly Powered Implantable Optical Stimulation Device.

This paper presents a mm-sized, free-floating, wirelessly powered, implantable optical stimulation (FF-WIOS) device for untethered optogenetic neuromodulation. A resonator-based three-coil inductive link creates a homogeneous magnetic field that continuously delivers sufficient power (>2.7 mW) at an optimal carrier frequency of 60 MHz to the FF-WIOS in the near field without surpassing the specific absorption rate limit, regardless of the position of the FF-WIOS in a large brain area. Forward data telemetry carries stimulation parameters by on-off-keying the power carrier at a data rate of 50 kb/s to selectively activate a 4 × 4 µLED array. Load-shift-keying back telemetry controls the wireless power transmission by reporting the FF-WIOS received power level in a closed-loop power control mechanism. LEDs typically require high instantaneous power to emit sufficient light for optical stimulation. Thus, a switched-capacitor-based stimulation architecture is used as an energy storage buffer with one off-chip capacitor to receive charge directly from the inductive link and deliver it to the selected µLED at the onset of stimulation. The FF-WIOS system-on-a-chip prototype, fabricated in a 0.35-µm standard CMOS process, charges a 10-µF capacitor up to 5 V with 37% efficiency and passes instantaneous current spikes up to 10 mA in the selected µLED, creating a bright exponentially decaying flash with minimal wasted power. An in vivo experiment was conducted to verify the efficacy of the FF-WIOS by observing light-evoked local field potentials and immunostained tissue response from the primary visual cortex (V1) of two anesthetized rats.

BDNF preserves the dendritic morphology of alpha and beta ganglion cells in the cat retina after optic nerve injury.

PURPOSE: To examine whether brain-derived neurotrophic factor (BDNF), a potent neuroprotectant in the mammalian retina, also plays a role in preserving the dendritic integrity of the surviving ganglion cells after optic nerve injury. METHODS: Single ganglion cells from cats that underwent unilateral optic nerve crush and received no treatment or nerve crush combined with intravitreous treatment of the affected eye with BDNF were labeled intracellularly, reconstructed using confocal microscopy, and compared quantitatively. RESULTS: Optic nerve injury produced a significant decrease in the soma, dendritic field size, and dendritic complexity of alpha cells. beta Cells also displayed a significant decrease in soma size, but their dendritic fields were not affected as severely as those of alpha cells. Intravitreous treatment of the eye with BDNF at the time of injury preserved the normal somal and dendritic morphologies of both alpha and beta cells. CONCLUSIONS: BDNF, in addition to promoting ganglion cell survival, plays an important role in preserving the somal and dendritic morphologies of the surviving ganglion cells, a necessary precursor to maintaining normal visual function. Ganglion cells, however, are not created equal with respect to their responses to nerve injury or to treatment of the eye with BDNF. Thus, development of effective treatment strategies for preserving ganglion cell function in optic nerve-related diseases mandates a clearer understanding of the cellular response characteristics of the specific neurons involved.