Metallothioneins, a Part of the Retinal Endogenous Protective System in Various Ocular Diseases.

Metallothioneins are the metal-rich proteins that play important roles in metal homeostasis and detoxification. Moreover, these proteins protect cells against oxidative stress, inhibit proapoptotic mechanisms and enhance cell differentiation and survival. Furthermore, MTs, mainly MT-1/2 and MT-3, play a vital role in protecting the neuronal retinal cells in the eye.

Deficiency of the RNA-binding protein ELAVL1/HuR leads to the failure of endogenous and exogenous neuroprotection of retinal ganglion cells.

Introduction: ELAVL1/HuR is a keystone regulator of gene expression at the posttranscriptional level, including stress response and homeostasis maintenance. The aim of this study was to evaluate the impact of silencing on the age-related degeneration of retinal ganglion cells (RGC), which potentially describes the efficiency of endogenous neuroprotection mechanisms, as well as to assess the exogenous neuroprotection capacity of -silenced RGC in the rat glaucoma model.

Methods: The study consisted of and approaches.

Rodent Models of Diabetic Retinopathy as a Useful Research Tool to Study Neurovascular Cross-Talk.

Diabetes is a group of metabolic diseases leading to dysfunction of various organs, including ocular complications such as diabetic retinopathy (DR). Nowadays, DR treatments involve invasive options and are applied at the sight-threatening stages of DR. It is important to investigate noninvasive or pharmacological methods enabling the disease to be controlled at the early stage or to prevent ocular complications.

SCD1-Fatty Acid Desaturase Inhibitor MF-438 Alleviates Latent Inflammation Induced by Preservative-Free Prostaglandin Analog Eye Drops.

Introduction: Prostaglandin analogs are the first line of treatment in patients with glaucoma. Recently, many preservative-free prostaglandin analogs have been marketed to increase their tolerance in chronic use. However, potentially safer formulations have been reported to induce inflammation within ocular surface and adnexa, associated with pronounced activation of tissue macrophages.

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration.

Retinal neurons are not able to undergo spontaneous regeneration in response to damage. A variety of stressors, i.e.

FluoroGold-Labeled Organotypic Retinal Explant Culture for Neurotoxicity Screening Studies.

Preclinical toxicity screening of the new retinal compounds is an absolute requirement in the pathway of further drug development. Since retinal neuron cultivation and in vivo studies are relatively expensive and time consuming, we aimed to create a fast and reproducible ex vivo system for retinal toxicity screening. For this purpose, we used rat retinal explant culture that was retrogradely labeled with the FluoroGold before the isolation.

Candidate proteins from predegenerated nerve exert time-specific protection of retinal ganglion cells in glaucoma.

Glaucoma is thought to be the main cause of severe visual impairment or permanent loss of vision. Current therapeutic strategies are not sufficient to protect against glaucoma. Thus, new therapies and potential novel therapeutic targets must be developed to achieve progress in the treatment of this insidious disease.

Increased intraocular pressure alters the cellular distribution of HuR protein in retinal ganglion cells - A possible sign of endogenous neuroprotection failure.

The RNA-binding protein, HuR, modulates mRNA processing and gene expression of several stress response proteins i.e. Hsp70 and p53 that have been postulated to be involved in the pathogenesis of glaucoma, a chronic optic neuropathy leading to irreversible blindness.

Predegenerated Schwann cells--a novel prospect for cell therapy for glaucoma: neuroprotection, neuroregeneration and neuroplasticity.

Glaucoma is an optic neuropathy that leads to irreversible blindness. Because the current therapies are not sufficient to protect against glaucoma-induced visual impairment, new treatment approaches are necessary to prevent disease progression. Cell transplantation techniques are currently considered to be among the most promising opportunities for nervous system damage treatment.

A rat experimental model of glaucoma incorporating rapid-onset elevation of intraocular pressure.

Glaucoma is a chronic disease that causes structural and functional damage to retinal ganglion cells (RGC). The currently employed therapeutic options are not sufficient to prevent vision loss in patients with glaucoma; therefore, there is a need to develop novel therapies, which requires the creation of functional, repeatable and easy-to-utilize animal models for use in pre-clinical studies. The currently available models ensure only low to moderate damage in optic nerves, with high variation in the outcomes and poor repeatability.

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat.

The purpose of the study was to examine the influence of the spatial variable magnetic field (induction: 150-300 µT, 80-150 µT, 20-80 µT; frequency 40 Hz) on neuropathic pain after tibial nerve transection. The experiments were carried out on 64 male Wistar C rats. The exposure of animals to magnetic field was performed 1 d/20 min.

Variable spatial magnetic field influences peripheral nerves regeneration in rats.

Generator of spatial magnetic field is one of most recent achievements among the magnetostimulators. This apparatus allows to obtain the rotating magnetic field. This new method may be more effective than other widely used techniques of magnetostimulation and magnetotherapy.

[The use of chitosan to facilitate nerve regeneration].

Chitosan, a biopolymer derived from chitin, biocompatible, biodegradable and antibacterial, has many medical applications. For more than a decade scientists have been studying the influence of chitosan on facilitating regeneration of peripheral nerves and neurons of central nervous system in animal models. First clinical attempts have also commenced.

Childhood pineal parenchymal tumors: clinical and therapeutic aspects.

The aim of our study was to investigate the correlation of the clinical characteristic of pineal parenchymal tumors in children and adolescent with histopathological diagnosis and patient survival. Records of 27 patients with histologically diagnosed pineocytomas (n=16) and pineoblastoma (n=11) consecutively treated between 1991 and 2001 were reviewed retrospectively to identify factors predictive of aggressiveness. Among analyzed epidemiological, clinical, and radiological factors, we found that independent prognostic indicator in patients with childhood pineal parenchymal tumor was the extent of surgical resection.

Neurotrophic activity of extracts from distal stumps of pre-degenerated peripheral rat nerves varies according to molecular mass spectrum.

Objective: We investigated neurotrophic activity of extracts from pre-degenerated and non-pre-degenerated peripheral nerves (complete extracts and extracts with fractions of narrower range of molecular weight) on the injured hippocampus.

Methods: The experiment was carried out on male Wistar C rats. The complete extracts or fractions with different ranges of molecular weight were introduced to the site of injury with the autologous connective tissue chambers.

The changes in neurotrophic properties of the peripheral nerves extracts following blocking of BDNF activity.

Objectives: Retinal ganglion cells (RGCs) of adult rats are unable to regenerate their axons after optic nerve injury and soon after they enter the pathway of apoptosis. They may, however, survive and regenerate new axons in response to application of specific peripheral nerve extracts that presumably contain a range of neurotrophic substances. One of the recognized substances of proven neurotrophic activity is brain-derived neurotrophic factor (BDNF).

Quantitative and qualitative analysis of proteins in rat peripheral nerves predegenerated for 7 days.

Objectives: In contrast to peripheral nerves, central neurons do not regrow spontaneously after injury. Our previous studies showed that transplantation of degenerating peripheral nerves or their extracts can induce regeneration in the injured central nervous system. Non-predegenerated nerves show much weaker neurotrophic activity.

[Metalloproteinases activity (MMP-2, MMP-9) in distal stumps of rat sciatic nerves].

In case of nerve transection we observed biochemical and morphological changes in axons. The aim of present study was to examine neurotrophic activity of two important metalloproteinases: MMP-2 and MMP-9. To examine their activity in nerve supernatants, gelatin zymography was used.

Influence of nerve growth factor upon the injured peripheral nerve in the absence of its distal part.

Transected peripheral nerve can be protected with different supplementations. One of them is implantation of dead-ended connective tissue chambers filled with fibrin and growth-promoting substances. The aim of this study was to find whether nerve growth factor (NGF) applied by means of such method exerts neuroprotective effect upon transected sciatic nerves.

[Current opinions on the pathogenesis of demyelinating diseases. Part II].

Demyelinating diseases include a group of disorders in which destruction or degeneration of normal myelin occurs. In most cases these processes go on without primary lesion of axons. Demyelinization appears as a consequence of different pathogenetic factors like ischemia, injury, toxins and radiation.

[Protein composition and structure of the myelin sheath. Part I].

During the past few years, significant advances have been made in meeting structure of myelin sheaths and the mechanisms participating in myelination and demyelination. Myelin is formed by Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Myelin is composed of several layers of membranes wrapped around axons.

Pre-degenerated peripheral nerve extracts applied to the proximal stump of transected sciatic nerve enhance both regeneration and autotomic behavior in rats.

Background: Peripheral nerve regeneration after traumatic injury and standard repair with a nerve autograft is often incomplete and results in neuropathic pain. Peripheral nerve extracts applied to the proximal nerve stump by means of autologous, dead-ended connective tissue chambers (deCTC) are known to accelerate the rate of axon regeneration. This study tested if such extracts would influence autotomy, which is a behavioral measure of neuropathic pain in animal models.