Mechanism of Cone Degeneration in Retinitis Pigmentosa

Song, De-Juan; Bao, Xiao-Li; Fan, Biao; Li, Guang-Yu

doi:10.1007/s10571-022-01243-2

Cited by 17 publications

(10 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Photoreceptor loss is the key pathogenesis and cause of vision loss in retinal degenerative diseases [3,4]. Among the multiple cell death mechanisms responsible for photoreceptor loss, apoptosis is considered to be the dominant mode in retinal degenerative diseases [5,8,46,47].…”

Section: Discussionmentioning

confidence: 99%

“…Retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa, are currently the major contributors to visual impairment and blindness, and there are no treatments available [1][2][3]. Photoreceptor loss is the main cause of vision loss in retinal degenerative diseases [4]. Although apoptosis, necroptosis, and ferroptosis play roles in the loss of photoreceptors in retinal degenerative diseases, apoptosis is still considered the primary cause [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Chen,

Xiong,

Deng

et al. 2023

The FEBS Journal

View full text Add to dashboard Cite

Photoreceptor apoptosis is the main pathological feature of retinal degenerative diseases; however, the underlying molecular mechanism has not been elucidated. Recent studies have shown that N‐myc downstream regulated gene 2 (NDRG2) exerts a neuroprotective effect on the brain and spinal cord. In addition, our previous studies have confirmed that NDRG2 is expressed in mouse retinal photoreceptors and counteracts N‐methyl‐N‐nitrosourea (MNU)‐induced apoptosis. However, the underlying molecular mechanism remains unclear. In this study, we observed that the expression of NDRG2 was not only significantly inhibited in photoreceptors after MNU treatment but also after hydrogen peroxide treatment, and photoreceptor apoptosis was alleviated or aggravated after overexpression or knockdown of NDRG2 in the 661W photoreceptor cell line, respectively. The apoptosis inhibitor Z‐VAD‐FMK rescued photoreceptor apoptosis induced by MNU after NDRG2 knockdown. Next, we screened and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as the downstream molecule of NDRG2 in 661W cells by using quantitative real‐time polymerase chain reaction. TIMP3 exerts a neuroprotective effect by inhibiting the expression of matrix metalloproteinases (MMPs). Subsequently, we found that signal transducer and activator of transcription 3 (STAT3) mediated the NDRG2‐associated regulation of TIMP3. Finally, we overexpressed NDRG2 in mouse retinal tissues by intravitreally injecting an adeno‐associated virus with mouse NDRG2 in vivo. Results showed that NDRG2 upregulated the expression of phospho‐STAT3 (p‐STAT3) and TIMP3, while suppressing MNU‐induced photoreceptor apoptosis and MMP expression. Our findings revealed how NDRG2 regulates the STAT3/TIMP3/MMP pathway and uncovered the molecular mechanism underlying its neuroprotective effect on mouse retinal photoreceptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Chen,

Xiong,

Deng

et al. 2023

The FEBS Journal

View full text Add to dashboard Cite

show abstract

“…In patients with RP, rod photoreceptors degenerate primarily due to genetic defects, followed by the slow degeneration of cone photoreceptors. The mechanism of cone degeneration remains unclear; however, non-autonomous mechanisms including oxidative stress, trophic factors, metabolic stress, light damage, and inflammation are suggested [ 9 ]. Early changes in cone degeneration include shortening or loss of outer segments, while cell bodies remain intact [ 10 ].…”

Section: Strategies and Target Cellsmentioning

confidence: 99%

Optogenetic Therapy for Visual Restoration

Sakai

Tomita

Maeda

2022

IJMS

View full text Add to dashboard Cite

Optogenetics is a recent breakthrough in neuroscience, and one of the most promising applications is the treatment of retinal degenerative diseases. Multiple clinical trials are currently ongoing, less than a decade after the first attempt at visual restoration using optogenetics. Optogenetic therapy has great value in providing hope for visual restoration in late-stage retinal degeneration, regardless of the genotype. This alternative gene therapy consists of multiple elements including the choice of target retinal cells, optogenetic tools, and gene delivery systems. Currently, there are various options for each element, all of which have been developed as a product of technological success. In particular, the performance of optogenetic tools in terms of light and wavelength sensitivity have been improved by engineering microbial opsins and applying human opsins. To provide better post-treatment vision, the optimal choice of optogenetic tools and effective gene delivery to retinal cells is necessary. In this review, we provide an overview of the advancements in optogenetic therapy for visual restoration, focusing on available options for optogenetic tools and gene delivery methods.

show abstract

“…Importantly, mitochondrial dysfunction of RPE cells leads to an increased reliance on glycolysis [ 8 , 29 ]. Consequently, less glucose is transported from the RPE to the retina, contributing to the death of PR cells [ 1 , 3 , 30 ]. Therefore, reprogramming retinal metabolism to restore the metabolic coupling between PRs and RPE cells has been proposed as a promising therapeutic strategy for retinal disorders [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy

Costa,

Quinn,

et al. 2024

Cell Biosci

View full text Add to dashboard Cite

Background Retinitis pigmentosa (RP) is a genetically heterogeneous group of degenerative disorders causing progressive vision loss due to photoreceptor death. RP affects other retinal cells, including the retinal pigment epithelium (RPE). MicroRNAs (miRs) are implicated in RP pathogenesis, and downregulating miR-181a/b has shown therapeutic benefit in RP mouse models by improving mitochondrial function. This study investigates the expression profile of miR-181a/b in RPE cells and the neural retina during RP disease progression. We also evaluate how miR-181a/b downregulation, by knocking out miR-181a/b-1 cluster in RPE cells, confers therapeutic efficacy in an RP mouse model and explore the mechanisms underlying this process. Results Our findings reveal distinct expression profiles, with downregulated miR-181a/b in RPE cells suggesting a protective response and upregulated miR-181a/b in the neural retina indicating a role in disease progression. We found that miR-181a/b-2, encoded in a separate genomic cluster, compensates for miR-181a/b-1 ablation in RPE cells at late time points. The transient downregulation of miR-181a/b in RPE cells at post-natal week 6 (PW6) led to improved RPE morphology, retarded photoreceptor degeneration and decreased RPE aerobic glycolysis. Conclusions Our study elucidates the underlying mechanisms associated with the therapeutic modulation of miR-181a/b, providing insights into the metabolic processes linked to its RPE-specific downregulation. Our data further highlights the impact of compensatory regulation between miR clusters with implications for the development of miR-based therapeutics. Graphical Abstract

show abstract

Mechanism of Cone Degeneration in Retinitis Pigmentosa

Cited by 17 publications

References 112 publications

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Optogenetic Therapy for Visual Restoration

Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy

Contact Info

Product

Resources

About