Device Design and Characteristics for SOA-basedAll Optical Signal 2R Regeneration

A new scheme based on SOA-MZI for all-optical 2R regeneration is proposed. The characteristics of gain and switching window of this device are investigated in detail. Numerical simulation results indicate that the nonlinear gain compression, the time delay between the input optical signal and the width of the optical pulse are essential parameters for a good performance of all-optical 2R regeneration.

Contribution to the Study of 2R Regenerators in Optical Transmission Link into Account the PMD

With the development of optical communication systems in high bandwidth fiber, various degradations affect the propagation of light signals such as polarization mode dispersion which represents a temporal pulse broadening, it becomes troublesome from long and long distances for this, it is necessary to regenerate the signal optically, that is to say, the amplified （1R regeneration） , the reshaping （2R regeneration） and sometimes resynchronize to overcome the phenomenon of jitter time （3R regeneration）. In this paper we study the contribution of 2R optical regenerator self-modulation to combat the phenomenon of polarization mode dispersion. The experiment is simulated with optisystem.

Complementary research in mammals and fish indicates MMP-2 as a pleiotropic contributor to optic nerve regeneration

Matrix metalloproteinases（MMPs）are members of the metzincin superfamily named after the zinc ion and the conserved methionine residue at the active site.In addition to their role in extracellular matrix（ECM）remodeling,these proteinases（in）activate many signaling molecules such as growth factors.

The progress in optic nerve regeneration, where are we?

Optic nerve regeneration is an important area of research. It can be used to treat patients suffering from optic neuropathy and provides insights into the treatment of numerous neurodegenerative diseases. There are many hurdles impeding optic regeneration in mammals. The mammalian central nervous system is non-permissive to regeneration and intrinsically lacks the capacity for axonal regrowth. Any axonal injury also triggers a vicious cycle of apoptosis. Understanding these hurdles provides us with a rough framework to appreciate the essential steps to bring about optic nerve regeneration： enhancing neuronal survival, axon regeneration, remyelination and establishing functional synapses to the original neuronal targets. In this review article, we will go through current potential treatments for optic nerve regeneration, which includes neurotrophic factor provision, inflammatory stimulation, growth inhibition suppression, intracellular signaling modification and modeling of bridging substrates.

ROCK inhibition as a novel potential strategy for axonal regeneration in optic neuropathies

Optic neuropathies or optic nerve diseases are a frequent cause of permanent vision loss that can occur after inflammation,ischemia,infection,tumors,trauma and/or an elevated pressure inside the eye（also called intraocular pressure or IOP）.

Calcium channel inhibition-mediated axonal stabilization improves axonal regeneration after optic nerve crush

Axonal projections are specialized neuronal compartments and the longest parts of neurons.Axonal degeneration is a common pathological feature in many neurodegenerative disorders,such as Parkinson’s disease,amyotrophic lateral sclerosis,glaucoma,as well as in traumatic lesions of the central nervous system（CNS）,such as spinal cord injury.

Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

AIM：To explore the effects of αA-crystallin in astrocyte gliosis after optic nerve crush（ONC） and the mechanism of α-crystallin in neuroprotection and axon regeneration.METHODS：ONC was established on the SpragueDawley rat model and αA-crystallin（10 -4 g/L,4 μL） was intravitreously injected into the rat model.Flash-visual evoked potential（F-VEP） was examined 14 d after ONC,and the glial fibrillary acidic protein（GFAP） levels in the retina and crush site were analyzed 1,3,5,7 and 14 d after ONC by immunohistochemistry（IHC） and Western blot respectively.The levels of beta Tubulin（TUJ1）,growth-associated membrane phosphoprotein-43（GAP-43）,chondroitin sulfate proteoglycans（CSPGs） and neurocan were also determined by IHC 14 d after ONC.RESULTS：GFAP level in the retina and the optic nerve significantly increased 1d after ONC,and reached the peak level 7d post-ONC.Injection of αA-crystallin significantly decreased GFAP level in both the retina and the crush site 3d after ONC,and induced astrocytes architecture remodeling at the crush site.Quantification of retinal ganglion cell（RGC） axons indicated αAcrystallin markedly promoted axon regeneration in ONC rats and enhanced the regenerated axons penetrated into the glial scar.CSPGs and neurocan expression also decreased 14 d after αA-crystallin injection.The amplitude（N1-P1） and latency（P1） of F-VEP were also restored.CONCLUSION：Our results suggest α-crystallin promotes the axon regeneration of RGCs and suppresses the activation of astrocytes.

Extrinsic regulation of optic nerve regeneration

Retinal ganglion cells(RGCs)extend through the optic nerve,connecting with neurons in visually related nuclei.Similar to most mature neurons in the central nervous system,once damaged,RGCs are unable to regenerate their axons and swiftly progress to cell death.In addition to cell-intrinsic mechanisms,extrinsic factors within the extracellular environment,notably glial and inflammatory cells,exert a pivotal role in modulating RGC neurodegeneration and regeneration.Moreover,burgeoning evidence suggests that retinal interneurons,specifically amacrine cells,exert a substantial influence on RGC survival and axon regeneration.In this review,we consolidate the present understanding of extrinsic factors implicated in RGC survival and axon regeneration,and deliberate on potential therapeutic strategies aimed at fostering optic nerve regeneration and restoring vision.

Optical Nonlinearity in a Novel Optical Signal Regeneration System Based on Cross-Gain Modulation Using Cascaded Semiconductor Optical Amplifiers

We propose a novel optical signal regeneration system based on wavelength converters by use of cross gain modulation in cascaded semiconductor optical amplifiers. The nonlinearity in optical input/output characteristics and eye opening using NRZ signal were archived.

Cell transplantation to replace retinal ganglion cells faces challenges-the Switchboard Dilemma

The mammalian retina displays incomplete intrinsic regenerative capacities;therefore,retina degeneration is a major cause of irreversible blindness such as glaucoma,agerelated macular degeneration and diabetic retinopathy.These diseases lead to the loss of retinal cells and serious vision loss in the late stage.Stem cell transplantation is a great promising novel treatment for these incurable retinal degenerative diseases and represents an exciting area of regenerative neurotherapy.Several suitable stem cell sources for transplantation including human embryonic stem cells,induced pluripotent stem cells and adult stem cells have been identified as promising target populations.However,the retina is an elegant neuronal complex composed of various types of cells with different functions.The replacement of these different types of cells by transplantation should be addressed separately.So far,retinal pigment epithelium transplantation has achieved the most advanced stage of clinical trials,while transplantation of retinal neurons such as retinal ganglion cells and photoreceptors has been mostly studied in pre-clinical animal models.In this review,we opine on the key problems that need to be addressed before stem cells transplantation,especially for replacing injured retinal ganglion cells,may be used practically for treatment.A key problem we have called the Switchboard Dilemma is a major block to have functional retinal ganglion cell replacement.We use the public switchboard telephone network as an example to illustrate different difficulties for replacing damaged components in the retina that allow for visual signaling.Retinal ganglion cell transplantation is confronted by significant hurdles,because retinal ganglion cells receive signals from different interneurons,integrate and send signals to the correct targets of the visual system,which functions similar to the switchboard in a telephone network-therefore the Switchboard Dilemma.

Human umbilical cord blood stem cells and brainderived neurotrophic factor for optic nerve injury: a biomechanical evaluation

Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10^6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation and creep properties of the optic nerve change after injury.Moreover,human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal.To validate this hypothesis,a rabbit model of optic nerve injury was established using a clamp approach.At 7 days after injury,the vitreous body received a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells.At 30 days after injury,stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly,with pathological changes in the injured optic nerve also noticeably improved.These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves,and thereby contributes to nerve recovery.

Synergetic effects of ciliary neurotrophic factor and olfactory ensheathing cells on optic nerve reparation(complete translation)

At present, there is no effective treatment for the repair of the optic nerve after injury, or improvement of its microenvironment for regeneration. Intravitreally injected ciliary neurotrophic factor（CNTF） and olfactory ensheathing cells（OECs） promote the long-distance regrowth of severed optic nerve fibers after intracranial injury. Here, we examined the efficacy of these techniques alone and in combination, in a rat model of optic nerve injury. We injected condensed OEC suspension at the site of injury, or CNTF into the vitreous body, or both simultaneously. Retrograde tracing techniques showed that 4 weeks postoperatively, the number of surviving retinal ganglion cells and their axonal density in the optic nerve were greater in rats subjected to OEC injection only than in those receiving CNTF injection only. Furthermore, combined OEC ＋ CNTF injection achieved better results than either monotherapy. These findings confirm that OECs are better than CNTF at protecting injured neurons in the eye, but that combined OEC and CNTF therapy is notably more effective than either treatment alone.

Macular thickness as a predictor of loss of visual sensitivity in ethambutol-induced optic neuropathy

Ethambutol is a common cause of drug-related optic neuropathy.Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss.Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function.Therefore,we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy.The thickness of peripapillary retinal nerve fiber layer,macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients（22 eyes） using optical coherence tomography.Twenty-four healthy age-and sex-matched participants（48 eyes） were used as controls.Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls.The average macular thickness was strongly positively correlated with central visual sensitivity loss（r2=0.878,P=0.000）.These findings suggest that optical coherence tomography can be used to efficiently screen patients.Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy.

Cell proliferation and apoptosis in optic nerve and brain integration centers of adult trout Oncorhynchus mykiss after optic nerve injury

Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve fibers after central nervous system injury.However,the underlying mechanism is poorly understood.In order to address this issue,we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves,after stab wound injury to the eye of an adult trout Oncorhynchus mykiss.Heterogenous population of proliferating cells was investigated at 1 week after injury.TUNEL labeling gave a qualitative and quantitative assessment of apoptosis in the cells of optic nerve of trout 2 days after injury.After optic nerve injury,apoptotic response was investigated,and mass patterns of cell migration were found.The maximal concentration of apoptotic bodies was detected in the areas of mass clumps of cells.It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia.At 1 week after optic nerve injury,we observed nerve cell proliferation in the trout brain integration centers：the cerebellum and the optic tectum.In the optic tectum,proliferating cell nuclear antigen（PCNA）-immunopositive radial glia-like cells were identified.Proliferative activity of nerve cells was detected in the dorsal proliferative（matrix） area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury.In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity,as evidenced by PCNA immunolabeling.Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1–4 days of culture.The present findings suggest that trout can be used as a novel model for studying neuronal regeneration.

Past,present and future of preserving and restoring function in the visual system:removing galectin-3 as a promising treatment

Great advances in retinal ganglion cells survival（RGCs）,optic nerve preservation and regeneration have been made in the past 15years.Nowadays,we know that RGCs are capable of regenerating the full length of the optic nerve,cross the chiasm,enter the brain and reinnervate visual targets.

Delayed treatment of secondary degeneration following acute optic nerve transection using a combination of ion channel inhibitors

Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca^2＋ entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO-@ pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery. In addition, all of the ion channel inhibitor treated rats were administered with calcium channel antagonist lomerizine hydrochloride. It is important to note that as a result of implantation of the particular pumps required for programmable delivery of therapeutics directly to the injury site, seromas occurred in a significant proportion of animals, indicating infection around the pumps in these animals. Improvements in visual function were observed only when treatment was delayed by 6 hours; phosphorylated Tau was reduced when treatment was delayed by 24 hours or 7 days. Improvements in structure of node/paranode of Ranvier and reductions in oxidative stress indicators were also only observed when treatment was delayed for 6 hours, 24 hours, or 7 days. Benefits of ion channel inhibitors were only observed with time-delayed treatment, suggesting that delayed therapy of Ca^2＋ ion channel inhibitors produces better neuroprotective effects on secondary degeneration, at least in the presence of seromas.

Advances in optic nerve regeneration and neuroprotection strategies

The most common irreversible blindness diseases are age-related macular degeneration, glaucoma, anddiabetic retinopathy which involve the optic nerve or retina. These diseases share a common condition of causing blindness - progressive neural cells loss of retina （photoreceptor ceils, retinal ganglion cells （RGCs））. Although many advances in the treatment for these diseases have been achieved in recent years, the visual function often cannot be reversed. To improve the visual outcomes, the retinal neuron cells must be rescued. Optic nerve diseases including glaucoma were mostly studied for the effort to rescue the injured neurons and regenerate the neuron axons.

Fiber soliton-form 3R regenerator and its performance analysis

A novel fiber optical 3R regenerator based on optical soliton-effect using highly nonlinear fiber is constructed and investigated for the needs of the high rate and long-haul optical communications. The propagation equation of the pulses in the proposed optical 3R regenerator with the control of optical modulator and filter is established. By the use of the variational approach, the evolution of the distorted optical pulses in the regenerator and the functions of reamplification, reshaping, and reUming are investigated. The relation between the construction parameters and the output performance of the regenerator is discussed. The stable operation condition of the regenerator is revealed.