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

Marita Pietrucha-Dutczak,Joanna Lewin-Kowalik,Xiaonan Liu,Markku Varjosalo,Iwona Matuszek,Adrian Smedowski

doi:10.1038/s41598-017-14860-5

Marita Pietrucha-Dutczak, Joanna Lewin-Kowalik + Show 4 more

Open Access

https://doi.org/10.1038/s41598-017-14860-5

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Abstract

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.

Highlights

Glaucoma is thought to be the main cause of severe visual impairment or permanent vision loss
We proved that protein extract obtained from predegenerated rat sciatic nerves stimulates retinal ganglion cells (RGCs) survival and promotes neurite outgrowth in a model of acute optic neuropathy – axotomy[18,19]
It seemed reasonable that when we successfully developed the rat model of chronic optic neuropathy, we should undertake efforts to verify the further neurotrophic potential of this extract

Summary

Introduction

Glaucoma is thought to be the main cause of severe visual impairment or permanent vision loss This type of optic neuropathy is characterized by damage to RGCs and their axons[1]. Neurotrophic activity was proved for fractions obtained from nerves predegenerated for 7 days[15,16,17] For this reason, we decided to use similar extract to verify its therapeutic activity in a glaucoma model and test whether the time-point of administration of extract as well as exposure time of this extract onto RGCs influences survival of these cells. We used our recently developed rat glaucoma model, which allows long-lasting IOP elevation with chronic damage of RGCs23,24. We performed the screening via an ex vivo test using a retinal explant culture model

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