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

Autor: Anna Wójcik-Gryciuk, Katarzyna Kordecka, Wioletta J. Waleszczyk, Małgorzata Skup, Paweł M. Boguszewski, Olga Gajewska-Woźniak
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Retinal Ganglion Cells
retina
trabecular occlusion
genetic structures
Glaucoma
Ocular hypertension
Tropomyosin receptor kinase B
lcsh:Chemistry
Neurotrophic factors
lcsh:QH301-705.5
Spectroscopy
TrkB receptor downregulation
General Medicine
Dependovirus
Computer Science Applications
medicine.anatomical_structure
Retinal ganglion cell
Intravitreal Injections
medicine.medical_specialty
Genetic Vectors
Neuroprotection
Retinal ganglion
Article
Catalysis
Inorganic Chemistry
Internal medicine
medicine
Animals
Humans
Receptor
trkB
Physical and Theoretical Chemistry
Molecular Biology
Retina
business.industry
Brain-Derived Neurotrophic Factor
Organic Chemistry
medicine.disease
eye diseases
Rats
Disease Models
Animal
Endocrinology
Gene Expression Regulation
nervous system
lcsh:Biology (General)
lcsh:QD1-999
microbeads
sense organs
business
BDNF overexpression
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 6262, p 6262 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 17
ISSN: 1661-6596
1422-0067
Popis: 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: OpenAIRE
Externí odkaz: