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Open AccessArticle

Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma

1
Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland
2
Mediq Clinic, 05-120 Legionowo, Poland
3
Group of Restorative Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland
4
Laboratory of Behavioral Methods, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Int. J. Mol. Sci. 2020, 21(17), 6262; https://doi.org/10.3390/ijms21176262
Received: 30 July 2020 / Revised: 26 August 2020 / Accepted: 27 August 2020 / Published: 29 August 2020
(This article belongs to the Special Issue Neuroprotective Strategies 2020)
Intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury (ONI) or laser-induced ocular hypertension (OHT). In models of glaucoma, BDNF therapy can delay or halt RGCs loss, but this protection is time-limited. The decreased efficacy of BDNF supplementation has been in part attributed to BDNF TrkB receptor downregulation. However, whether BDNF overexpression causes TrkB downregulation, impairing long-term BDNF signaling in the retina, has not been conclusively proven. After ONI or OHT, when increased retinal BDNF was detected, a concomitant increase, no change or a decrease in TrkB was reported. We examined quantitatively the retinal concentrations of the TrkB protein in relation to BDNF, in a course of adeno-associated viral vector gene therapy (AAV2-BDNF), using a microbead trabecular occlusion model of glaucoma. We show that unilateral glaucoma, with intraocular pressure ( IOP) increased for five weeks, leads to a bilateral decrease of BDNF in the retina at six weeks, accompanied by up to four-fold TrkB upregulation, while a moderate BDNF overexpression in a glaucomatous eye triggers changes that restore normal TrkB concentrations, driving signaling towards long-term RGCs neuroprotection. We conclude that for glaucoma therapy, the careful selection of the appropriate BDNF concentration is the main factor securing the long-term responsiveness of RGCs and the maintenance of normal TrkB levels. View Full-Text
Keywords: retina; BDNF overexpression; TrkB receptor downregulation; trabecular occlusion; microbeads retina; BDNF overexpression; TrkB receptor downregulation; trabecular occlusion; microbeads
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MDPI and ACS Style

Wójcik-Gryciuk, A.; Gajewska-Woźniak, O.; Kordecka, K.; Boguszewski, P.M.; Waleszczyk, W.; Skup, M. Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma. Int. J. Mol. Sci. 2020, 21, 6262. https://doi.org/10.3390/ijms21176262

AMA Style

Wójcik-Gryciuk A, Gajewska-Woźniak O, Kordecka K, Boguszewski PM, Waleszczyk W, Skup M. Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma. International Journal of Molecular Sciences. 2020; 21(17):6262. https://doi.org/10.3390/ijms21176262

Chicago/Turabian Style

Wójcik-Gryciuk, Anna; Gajewska-Woźniak, Olga; Kordecka, Katarzyna; Boguszewski, Paweł M.; Waleszczyk, Wioletta; Skup, Małgorzata. 2020. "Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma" Int. J. Mol. Sci. 21, no. 17: 6262. https://doi.org/10.3390/ijms21176262

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