| Autor: |
Wójcik-Gryciuk A; Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.; Mediq Clinic, 05-120 Legionowo, Poland., Gajewska-Woźniak O; Group of Restorative Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland., Kordecka K; Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland., Boguszewski PM; Laboratory of Behavioral Methods, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland., Waleszczyk W; Laboratory of Neurobiology of Vision, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland., Skup M; Group of Restorative Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2020 Aug 29; Vol. 21 (17). Date of Electronic Publication: 2020 Aug 29. |
| DOI: |
10.3390/ijms21176262 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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