Evidence map›Paper›PMID 26200341›Full record

ArticleNature2015

Lanosterol reverses protein aggregation in cataracts.

Ling Zhao, Xiang-Jun Chen, Jie Zhu, Yi-Bo Xi, Xu Yang, Li-Dan Hu, Hong Ouyang, Sherrina H Patel, Xin Jin, Danni Lin and 33 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 189 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 2 pooled it
18.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 444 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  12. Preventing Age-Related Nuclear Cataract Development - Is Cholesterol the Key?Investigative ophthalmology & visual science · 2026
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  18. Article
  19. Review
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129 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 11 institutions in 3 countries.

Ling Zhao1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Xiang-Jun ChenState Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Jie Zhu1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Yi-Bo XiState Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xu YangBGI-Shenzhen, Shenzhen 518083, China.
Li-Dan HuState Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Hong Ouyang1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Sherrina H PatelDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Xin JinBGI-Shenzhen, Shenzhen 518083, China.
Danni LinDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Frances WuDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Ken FlaggDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Huimin Cai1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China.
Gen LiMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Guiqun CaoMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Ying Lin1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Daniel ChenDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Cindy WenDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Christopher ChungDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Yandong WangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Austin Qiu1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] CapitalBio Genomics Co., Ltd., Dongguan 523808, China.
Emily YehDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Wenqiu Wang1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China.
Xun HuMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Seanna GrobDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Ruben AbagyanSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA.
Zhiguang SuMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Harry Christianto TjondroState Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xi-Juan ZhaoState Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Hongrong LuoDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Rui HouGuangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China.
J Jefferson
P PerryDepartment of Biochemistry, University of California Riverside, Riverside, California 92521, USA.
Weiwei Gao1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA.
Igor KozakKing Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
David GranetDepartment of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Yingrui LiBGI-Shenzhen, Shenzhen 518083, China.
Xiaodong SunDepartment of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China.
Jun WangBGI-Shenzhen, Shenzhen 518083, China.
Liangfang Zhang1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA.
Yizhi LiuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Yong-Bin YanDepartment of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Kang Zhang1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [4] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.
University of California, San Diego · USTsinghua University · CNBGI Group (China) · CNSun Yat-sen University · CNSichuan University · CNState Key Laboratory of BiotherapyKing Khaled Eye Specialist Hospital · SAShanghai Jiao Tong University · CNUniversity of California, Riverside · USUniversity of Montana · USXijing Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.

Indexed as

AdultAmino Acid SequenceAmyloidAnimalsBase SequenceCataractCell LineChildCrystallinsDogsFemaleHumansLanosterolLens, CrystallineMaleModels, MolecularAmyloidCrystallinsLanosterolMutant ProteinsProtein Aggregates

Identifiers

PMID26200341
OpenAlexW1564028006

What OpenQuestion holds

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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 OpenQuestion graph.