Evidence mapPaperPMID 41784335Full record

ArticleInvestigative ophthalmology & visual science2026

Neuropilin-2 Deficiency Promotes Mitochondrial Dysfunction and NAD⁺-Dependent Cellular Senescence in Retinal Degeneration.

Lechun Ou, Baoyue Cui, Linbin Zhou, Keli Liu, Le Shi, Tian Zhou, Lei Zeng, Hong Zhou, Huiyi Xu, Yingfeng Zheng and 7 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Lechun OuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Baoyue CuiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Linbin ZhouDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Keli LiuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Le ShiWilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States.
Tian ZhouState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Lei ZengState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Hong ZhouState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Huiyi XuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Yingfeng ZhengState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Xiaolai ZhouState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Xuri LiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Chang HeState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Wei YiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Feng ZhangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Rong JuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Xialin LiuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Retinal pigment epithelial (RPE) dysfunction is a central pathological feature of retinal degenerative diseases, leading to irreversible vision loss. RPE dysfunction is substantially driven by mitochondrial impairment and senescence. However, the upstream regulators of these processes remain largely undefined. This study investigated the role of neuropilin-2 (NRP2) in RPE homeostasis and explored mitochondrial-targeted therapy with echinacoside (ECH) as a potential intervention for retinal degeneration. Methods: RPE-specific Nrp2 conditional knockout mice were generated using AAV-VMD2-Cre and retinal morphology and function were assessed by fundus imaging, optical coherence tomography, histology, and electroretinogram (ERG). Cellular and metabolic phenotypes were examined in NRP2-deficient ARPE-19 cells and validated in vivo. RPE senescence, mitochondrial function, NAD⁺ metabolism, and sirtuin activity were analyzed, and the effects of ECH treatment were evaluated both in vitro and in vivo. Results: RPE-specific Nrp2 deletion resulted in progressive RPE atrophy, photoreceptor loss, and impaired ERG responses. NRP2 deficiency led to mitochondrial elongation, elevated ROS, membrane depolarization, and reduced NAD⁺/NADH ratios. Decreased NAD⁺ levels were accompanied by downregulation of SIRT1/SIRT3 and increased protein acetylation, promoting RPE senescence. Restoring NAD⁺ levels or ECH treatment rescued mitochondrial dysfunction and reduced senescence markers in vitro. Furthermore, in vivo ECH administration preserved retinal structure and visual function in NRP2-deficient mice. Conclusions: NRP2 is a critical regulator of mitochondrial integrity and NAD⁺ metabolism in the RPE. Its loss disrupts metabolic homeostasis, promoting RPE senescence and retinal degeneration. Targeting the NRP2-mitochondria-NAD⁺ axis with echinacoside represents a promising therapeutic strategy for preventing retinal degenerative diseases.

Indexed as

Cellular SenescenceMitochondriaNADNeuropilin-2Retinal DegenerationRetinal Pigment EpitheliumAnimalsBlotting, WesternDisease Models, AnimalElectroretinographyHumansMiceMice, Inbred C57BLMice, KnockoutReactive Oxygen SpeciesTomography, Optical CoherenceNADNeuropilin-2Reactive Oxygen Species

Identifiers

PMID41784335
PMCPMC12967115

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.