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Protection of retinal function and morphology in MNU-induced retinitis pigmentosa rats by ALDH2: an in-vivo study
- Source :
- BMC Ophthalmology, BMC Ophthalmology, Vol 20, Iss 1, Pp 1-10 (2020)
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
Abstract
- Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats. Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted. Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein. Conclusions Together, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.
- Subjects :
- Male
Poly (ADP-Ribose) Polymerase-1
Aldehyde dehydrogenase
Rats, Sprague-Dawley
chemistry.chemical_compound
lcsh:Ophthalmology
Sirtuin 1
Photoreceptor degeneration
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
biology
Aldehyde Dehydrogenase, Mitochondrial
Neurodegeneration
Methylnitrosourea
General Medicine
Electroretinogram
Retinitis pigmentosa
Benzamides
Endoplasmic reticulum stress
Injections, Intraperitoneal
Tomography, Optical Coherence
Research Article
medicine.medical_specialty
Alkylating Agents
Blotting, Western
Dark Adaptation
Retina
SIRT1
Downregulation and upregulation
Internal medicine
medicine
Electroretinography
Animals
Benzodioxoles
ALDH2
business.industry
Endoplasmic reticulum
Retinal
medicine.disease
Rats
Ophthalmology
Disease Models, Animal
Endocrinology
chemistry
Apoptosis
lcsh:RE1-994
biology.protein
business
Photic Stimulation
Subjects
Details
- Language :
- English
- ISSN :
- 14712415
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- BMC Ophthalmology
- Accession number :
- edsair.doi.dedup.....9aaa462181f5bdb15e468ae7738c3eab