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

Abstract

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. The beneficial effects of undifferentiated cells have been investigated in experimental models of glaucoma, however experiments were accompanied by various barriers, which would make putative treatment difficult or even impossible to apply in a clinical setting. The novel therapy proposed in our study creates conditions to eliminate some of the identified barriers described for precursor cells transplantation and allows us to observe direct neuroprotective and pro-regenerative effects in ongoing optic neuropathy without additional modifications to the transplanted cells. We demonstrated that the proposed novel Schwann cell therapy might be promising, effective and easy to apply, and is safer than the alternative cell therapies for the treatment of glaucoma.

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

“…IOP was measured using a tonometer (TonoLab, Icare, Finland) before bead injection at 1, 3 and 7 days after injection and once per week until animals were sacrificed. The obtained values of IOP were comparable with those described in previous study thereby ensuring the reproducibility of the model 23 , 24 . The right eye was used as a healthy control.…”

“…Experimental glaucoma was induced unilaterally (the left eye) based on modified bead model with initial high pressure injury, as described before 23 , 24 . We used forty-three male Wistar rats (see detailed description of subgroups on Fig.…”

“…Furthermore we examined changes in the expression of endogenous BDNF after application of extract. We used our recently developed rat glaucoma model, which allows long-lasting IOP elevation with chronic damage of RGCs 23 , 24 . Moreover, we have analysed the protein composition of the extract from nerves predegenerated for 7 days by mass spectrometry and compare to the extracts obtained from non-predegenerated nerves as well as the nerves following longer-lasting predegeneration (i.e., 14 days).…”

FluoroGold‐Labeled Organotypic Retinal Explant Culture for Neurotoxicity Screening Studies

“…There are different approaches to prepare and maintain the retinal cultures, differing from the point of view of tissue separation, size of retinal pieces, and preferable culture medium [ 21 , 23 , 30 , 38 , 40 – 44 ]. In our study, we used a model based on rat retinal explants cultured in Neurobasal A medium described previously by Johnson et al, since it provides a good survival of retinal neurons after seven days [ 30 , 45 ]. From our culture protocol, we excluded supplementation with streptomycin, because another aminoglycoside antibiotic (gentamicin) was applied as our tested agent.…”

New perspectives of immunomodulation and neuroprotection in glaucoma

“…The SC homogenate without NTFs such as NGF, BDNF, CNTF, NT3 has been administered in retinal insert explants and intravitreal injections. It was found to have a positive effect for RGC protection and regeneration as axon regrowth, in spite of the absence of NTF supplementation [ 61 ].…”