Protection of retinal function and morphology in MNU-induced retinitis pigmentosa rats by ALDH2: an in-vivo study

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.

Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology

“…Furthermore, we confirmed the retinal protective ability of the RdECM using the Laser-CNV and the NMU-RD model due to their wide use as retinal degeneration models, including AMD and RP [ 55 , 56 , 57 , 58 ]. The RdECM-treated Laser-CNV mice showed similar wound recovery as the Avastin-treated mice, whereas the recovery was nearly unchanged in the collagen-treated mice.…”

Protective effect of aldehyde dehydrogenase 2 against rat corneal dysfunction caused by streptozotocin-induced type I diabetes

“…27 Moreover, our recent study showed that ALDH2 could protect retinal function and morphology in rats with MNU-induced retinitis pigmentosa. 28 This evidence supports a beneficial role of ALDH2 in endothelial dysfunction, angiogenesis, neurodegeneration, and energy metabolism disturbance.…”

ALDH2 protects naturally aged mouse retina via inhibiting oxidative stress-related apoptosis and enhancing unfolded protein response in endoplasmic reticulum

“…Moreover, ALDH2 has a certain protective effect in age-related disease, such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and aged cardiopathy by decreasing free radicals damage [ 20 ]. Simultaneously, our previous animal experiments have also shown that ALDH2 could play a certain role in aged diabetic retinopathy [ 21 ] and retinitis pigmentosa (RP) [ 22 ]. Furthermore, our clinical retrospective data analysis showed that the aged with ALDH2*1* (G/G) genotype possessed a better retinal function and a thicker macula compared with ALDH2*2*2 (mutant heterozygous AA) while the young with different ALDH2 genotype, including ALDH2*1*1, ALDH2*1*2 (mutant heterozygous GA) and ALDH2*2*2, showed no significant difference ( Supplementary Figure 1 ).…”