Retinal neurons are not able to undergo spontaneous regeneration in response to damage. A variety of stressors, i.e., UV radiation, high temperature, ischemia, allergens, and others, induce reactive oxygen species production, resulting in consecutive alteration of stress-response gene expression and finally can lead to cell apoptosis. Neurons have developed their own endogenous cellular protective systems. Some of them are preventing cell death and others are allowing functional recovery after injury. The high efficiency of these mechanisms is crucial for cell survival. In this review we focus on the contribution of the most recently studied endogenous neuroprotective factors involved in retinal ganglion cell (RGC) survival, among which, neurotrophic factors and their signaling pathways, processes regulating the redox status, and different pathways regulating cell death are the most important. Additionally, we summarize currently ongoing clinical trials for therapies for RGC degeneration and optic neuropathies, including glaucoma. Knowledge of the endogenous cellular protective mechanisms may help in the development of effective therapies and potential novel therapeutic targets in order to achieve progress in the treatment of retinal and optic nerve diseases.

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. We have developed an effective and reproducible rat glaucoma model based on a previous idea for a “Bead Model” in mice, which could be useful in future glaucoma research. Additionally, in an attempt to achieve rapid elevation of Intraocular Pressure (IOP), we included an initial “high-pressure injury” as part of this method, which serves as the equivalent of a severe glaucoma attack. These modifications made it possible to achieve longer lasting IOP elevation with chronic damage of retinal ganglion cells.

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. This study was undertaken to verify whether the time of administration of an extract from predegenerated rat sciatic nerves as well as exposure time of this extract onto retinal ganglion cells (RGCs) influences the survival of RGCs in a rat glaucoma model. We have demonstrated that extract obtained from the predegenerated sciatic nerves protects RGCs in a rat glaucoma model. The neuroprotective effect depends mostly on the time of administration of the extract and less clearly on the time of exposure to the extract and is associated with stimulation of endogenous BDNF expression both in RGCs and glial cells. The 14th day following glaucoma induction represents a therapeutic window for effective treatment in a glaucoma model. Mass Spectrometry analysis demonstrated that metallothionein 2 (MT2) may be a key molecule responsible for neuroprotective effects on RGC survival.

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. We investigated the influence of alternating, spatial magnetic field on the regeneration of the crushed rat sciatic nerves. Functional and morphological evaluations were used. After crush injury of the right sciatic nerve, Wistar C rats (n = 80) were randomly divided into four groups (control and three experimental). The experimental groups (A, B, C) were exposed (20 min/day, 5 d/week, 4 weeks) to alternating spatial magnetic field of three different intensities. Sciatic Functional Index (SFI) and tensometric assessments were performed every week after nerve crush. Forty-eight hours before the sacrificing of animals, DiI (1,1'-di-octadecyl-3,3,3',3'-tetramethyloindocarbocyanine perchlorate) was applied 5 mm distally to the crush site. Collected nerves and dorsal root ganglia (DRG) were subjected to histological and immunohistochemical staining. The survival rate of DRG neurons was estimated. Regrowth and myelination of the nerves was examined. The results of SFI and tensometric assessment showed improvement in all experimental groups as compared to control, with best outcome observed in group C, exposed to the strongest magnetic field. In addition, DRG survival rate and nerve regeneration intensity were significantly higher in the C group. Above results indicate that strong spatial alternating magnetic field exerts positive effect on peripheral nerve regeneration and its application could be taken under consideration in the therapy of injured peripheral nerves.

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