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Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti’s crystalline dystrophy
Purpose Abnormalities in lipid metabolism have been proposed in Bietti’s crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study. Methods All participants were genetically confirmed by CYP4V2 gene sequencing and underwent chorioretinopathy evaluation by calcula...
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| Published in: | Graefe's archive for clinical and experimental ophthalmology 2024-12, Vol.262 (12), p.3773-3786 |
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| creator | Li, Qian Wang, Cong Zhang, Shengjuan Fu, Zhongjie Jiao, Xiaodong Jin, Zibing Hejtmancik, J. Fielding Miao, Huan Qi, Simeng Peng, Xiaoyan |
| description | Purpose
Abnormalities in lipid metabolism have been proposed in Bietti’s crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study.
Methods
All participants were genetically confirmed by
CYP4V2
gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites.
Results
Routine lipids profiles showed elevated plasma levels of triglyceride (
P
= 0.043) and low-density lipoprotein cholesterol (
P
= 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6,
P
= 0.00068) and eicosapentaenoic acid (EPA, 20:5,
P
= 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4,
P
|
| doi_str_mv | 10.1007/s00417-024-06554-2 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3075704150</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3134402672</sourcerecordid><originalsourceid>FETCH-LOGICAL-c256t-86735fdac5bcd722ec373f41d8c1ed27d2a4095debe52dd31faaf356ac97a6213</originalsourceid><addsrcrecordid>eNp9kU1OHDEQha0IFCaQC2QRWWKTTQf_tmeWgCBEQmIDEjvLbVcTkx67Y7sRI2XBNXK9nAQPQ4jEgpVLru-9sush9ImSr5QQdZAJEVQ1hImGtFKKhr1DMyq4bBRh11toRhSjzZyz6x30IedbUnku6Xu0w-eLlouWzNDvS5NuoIDDgx-9i0tvM56CjXeQMo73q_V1wCOkMqXOFB9DxiY4PMYCoXgzYOuTnYanFu58XJr0c62tqiMPpfi_D38ytmmVixkGHwC7WqY4_ljtoe3eDBk-Pp-76Or05PL4rDm_-Pb9-PC8sUy2pZm3isveGSs76xRjYLnivaBubik4phwzgiykgw4kc47T3piey9bYhTIto3wXfdn4jin-miAXvfTZwjCYAHHKmhMlVd2lJBXdf4XeximF-jrNKReCsFaxSrENZVPMOUGvx-Trx1eaEr3ORm-y0TUb_ZSNXos-P1tP3RLci-RfGBXgGyDXVriB9H_2G7aP4DWe1w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3134402672</pqid></control><display><type>article</type><title>Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti’s crystalline dystrophy</title><source>Springer Nature</source><creator>Li, Qian ; Wang, Cong ; Zhang, Shengjuan ; Fu, Zhongjie ; Jiao, Xiaodong ; Jin, Zibing ; Hejtmancik, J. Fielding ; Miao, Huan ; Qi, Simeng ; Peng, Xiaoyan</creator><creatorcontrib>Li, Qian ; Wang, Cong ; Zhang, Shengjuan ; Fu, Zhongjie ; Jiao, Xiaodong ; Jin, Zibing ; Hejtmancik, J. Fielding ; Miao, Huan ; Qi, Simeng ; Peng, Xiaoyan</creatorcontrib><description>Purpose
Abnormalities in lipid metabolism have been proposed in Bietti’s crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study.
Methods
All participants were genetically confirmed by
CYP4V2
gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites.
Results
Routine lipids profiles showed elevated plasma levels of triglyceride (
P
= 0.043) and low-density lipoprotein cholesterol (
P
= 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6,
P
= 0.00068) and eicosapentaenoic acid (EPA, 20:5,
P
= 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4,
P
< 0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (
P
< 0.0001) between BCD patients and controls. Genotypes of
CYP4V2
, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites including 5-HETE, 5-HEPE, 12-HEPE and LTB4.
Conclusions
BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream metabolites via the COX and LOX pathways, suggesting that these might be implicated in BCD pathogenesis and could serve as biomarkers and therapeutic targets of the disease.
Key messages
What is known
BCD is a vision-threatening hereditary disease the causative gene of which is
CYP4V2
.
Abnormalities in lipid metabolism have been proposed and demonstrated previously in BCD studies.
The detailed pathogenesis remains unclear and controversial.
What is new
We observed prominent lipidomic alterations in the circulation when compared with age, gender, and bodymass index (BMI)-matched healthy controls.
BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA).
Remarkable changes were observed in the downstream metabolites of the LCPUFA via the COX and LOX pathways.
Genotypes of
CYP4V2
, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites.</description><identifier>ISSN: 0721-832X</identifier><identifier>ISSN: 1435-702X</identifier><identifier>EISSN: 1435-702X</identifier><identifier>DOI: 10.1007/s00417-024-06554-2</identifier><identifier>PMID: 38963460</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Arachidonic acid ; Atrophy ; Biomarkers ; Biomarkers - blood ; Biomarkers - metabolism ; Case-Control Studies ; Cholesterol ; Corneal Dystrophies, Hereditary - blood ; Corneal Dystrophies, Hereditary - diagnosis ; Corneal Dystrophies, Hereditary - genetics ; Corneal Dystrophies, Hereditary - metabolism ; Cytochrome P450 Family 4 - genetics ; Cytochrome P450 Family 4 - metabolism ; DNA - genetics ; Docosahexaenoic acid ; Dystrophy ; Eicosapentaenoic acid ; Female ; Genotypes ; Hereditary diseases ; Humans ; Lipid metabolism ; Lipid Metabolism - physiology ; Lipidomics - methods ; Lipids ; Lipoxygenase ; Male ; Medicine ; Medicine & Public Health ; Metabolism ; Metabolites ; Middle Aged ; Mutation ; Ophthalmology ; Oxylipins - blood ; Pathogenesis ; Plasma ; Plasma levels ; Polyunsaturated fatty acids ; Prostaglandin E2 ; Prostaglandin endoperoxide synthase ; Retinal Diseases - blood ; Retinal Diseases - diagnosis ; Retinal Diseases - genetics ; Retinal Diseases - metabolism ; Retinal Disorders ; Therapeutic targets</subject><ispartof>Graefe's archive for clinical and experimental ophthalmology, 2024-12, Vol.262 (12), p.3773-3786</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c256t-86735fdac5bcd722ec373f41d8c1ed27d2a4095debe52dd31faaf356ac97a6213</cites><orcidid>0000-0002-4275-6856 ; 0000-0003-0613-9591</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38963460$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Wang, Cong</creatorcontrib><creatorcontrib>Zhang, Shengjuan</creatorcontrib><creatorcontrib>Fu, Zhongjie</creatorcontrib><creatorcontrib>Jiao, Xiaodong</creatorcontrib><creatorcontrib>Jin, Zibing</creatorcontrib><creatorcontrib>Hejtmancik, J. Fielding</creatorcontrib><creatorcontrib>Miao, Huan</creatorcontrib><creatorcontrib>Qi, Simeng</creatorcontrib><creatorcontrib>Peng, Xiaoyan</creatorcontrib><title>Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti’s crystalline dystrophy</title><title>Graefe's archive for clinical and experimental ophthalmology</title><addtitle>Graefes Arch Clin Exp Ophthalmol</addtitle><addtitle>Graefes Arch Clin Exp Ophthalmol</addtitle><description>Purpose
Abnormalities in lipid metabolism have been proposed in Bietti’s crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study.
Methods
All participants were genetically confirmed by
CYP4V2
gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites.
Results
Routine lipids profiles showed elevated plasma levels of triglyceride (
P
= 0.043) and low-density lipoprotein cholesterol (
P
= 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6,
P
= 0.00068) and eicosapentaenoic acid (EPA, 20:5,
P
= 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4,
P
< 0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (
P
< 0.0001) between BCD patients and controls. Genotypes of
CYP4V2
, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites including 5-HETE, 5-HEPE, 12-HEPE and LTB4.
Conclusions
BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream metabolites via the COX and LOX pathways, suggesting that these might be implicated in BCD pathogenesis and could serve as biomarkers and therapeutic targets of the disease.
Key messages
What is known
BCD is a vision-threatening hereditary disease the causative gene of which is
CYP4V2
.
Abnormalities in lipid metabolism have been proposed and demonstrated previously in BCD studies.
The detailed pathogenesis remains unclear and controversial.
What is new
We observed prominent lipidomic alterations in the circulation when compared with age, gender, and bodymass index (BMI)-matched healthy controls.
BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA).
Remarkable changes were observed in the downstream metabolites of the LCPUFA via the COX and LOX pathways.
Genotypes of
CYP4V2
, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites.</description><subject>Adult</subject><subject>Arachidonic acid</subject><subject>Atrophy</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - metabolism</subject><subject>Case-Control Studies</subject><subject>Cholesterol</subject><subject>Corneal Dystrophies, Hereditary - blood</subject><subject>Corneal Dystrophies, Hereditary - diagnosis</subject><subject>Corneal Dystrophies, Hereditary - genetics</subject><subject>Corneal Dystrophies, Hereditary - metabolism</subject><subject>Cytochrome P450 Family 4 - genetics</subject><subject>Cytochrome P450 Family 4 - metabolism</subject><subject>DNA - genetics</subject><subject>Docosahexaenoic acid</subject><subject>Dystrophy</subject><subject>Eicosapentaenoic acid</subject><subject>Female</subject><subject>Genotypes</subject><subject>Hereditary diseases</subject><subject>Humans</subject><subject>Lipid metabolism</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipidomics - methods</subject><subject>Lipids</subject><subject>Lipoxygenase</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Ophthalmology</subject><subject>Oxylipins - blood</subject><subject>Pathogenesis</subject><subject>Plasma</subject><subject>Plasma levels</subject><subject>Polyunsaturated fatty acids</subject><subject>Prostaglandin E2</subject><subject>Prostaglandin endoperoxide synthase</subject><subject>Retinal Diseases - blood</subject><subject>Retinal Diseases - diagnosis</subject><subject>Retinal Diseases - genetics</subject><subject>Retinal Diseases - metabolism</subject><subject>Retinal Disorders</subject><subject>Therapeutic targets</subject><issn>0721-832X</issn><issn>1435-702X</issn><issn>1435-702X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kU1OHDEQha0IFCaQC2QRWWKTTQf_tmeWgCBEQmIDEjvLbVcTkx67Y7sRI2XBNXK9nAQPQ4jEgpVLru-9sush9ImSr5QQdZAJEVQ1hImGtFKKhr1DMyq4bBRh11toRhSjzZyz6x30IedbUnku6Xu0w-eLlouWzNDvS5NuoIDDgx-9i0tvM56CjXeQMo73q_V1wCOkMqXOFB9DxiY4PMYCoXgzYOuTnYanFu58XJr0c62tqiMPpfi_D38ytmmVixkGHwC7WqY4_ljtoe3eDBk-Pp-76Or05PL4rDm_-Pb9-PC8sUy2pZm3isveGSs76xRjYLnivaBubik4phwzgiykgw4kc47T3piey9bYhTIto3wXfdn4jin-miAXvfTZwjCYAHHKmhMlVd2lJBXdf4XeximF-jrNKReCsFaxSrENZVPMOUGvx-Trx1eaEr3ORm-y0TUb_ZSNXos-P1tP3RLci-RfGBXgGyDXVriB9H_2G7aP4DWe1w</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Li, Qian</creator><creator>Wang, Cong</creator><creator>Zhang, Shengjuan</creator><creator>Fu, Zhongjie</creator><creator>Jiao, Xiaodong</creator><creator>Jin, Zibing</creator><creator>Hejtmancik, J. Fielding</creator><creator>Miao, Huan</creator><creator>Qi, Simeng</creator><creator>Peng, Xiaoyan</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4275-6856</orcidid><orcidid>https://orcid.org/0000-0003-0613-9591</orcidid></search><sort><creationdate>20241201</creationdate><title>Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti’s crystalline dystrophy</title><author>Li, Qian ; Wang, Cong ; Zhang, Shengjuan ; Fu, Zhongjie ; Jiao, Xiaodong ; Jin, Zibing ; Hejtmancik, J. Fielding ; Miao, Huan ; Qi, Simeng ; Peng, Xiaoyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-86735fdac5bcd722ec373f41d8c1ed27d2a4095debe52dd31faaf356ac97a6213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Arachidonic acid</topic><topic>Atrophy</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - metabolism</topic><topic>Case-Control Studies</topic><topic>Cholesterol</topic><topic>Corneal Dystrophies, Hereditary - blood</topic><topic>Corneal Dystrophies, Hereditary - diagnosis</topic><topic>Corneal Dystrophies, Hereditary - genetics</topic><topic>Corneal Dystrophies, Hereditary - metabolism</topic><topic>Cytochrome P450 Family 4 - genetics</topic><topic>Cytochrome P450 Family 4 - metabolism</topic><topic>DNA - genetics</topic><topic>Docosahexaenoic acid</topic><topic>Dystrophy</topic><topic>Eicosapentaenoic acid</topic><topic>Female</topic><topic>Genotypes</topic><topic>Hereditary diseases</topic><topic>Humans</topic><topic>Lipid metabolism</topic><topic>Lipid Metabolism - physiology</topic><topic>Lipidomics - methods</topic><topic>Lipids</topic><topic>Lipoxygenase</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Ophthalmology</topic><topic>Oxylipins - blood</topic><topic>Pathogenesis</topic><topic>Plasma</topic><topic>Plasma levels</topic><topic>Polyunsaturated fatty acids</topic><topic>Prostaglandin E2</topic><topic>Prostaglandin endoperoxide synthase</topic><topic>Retinal Diseases - blood</topic><topic>Retinal Diseases - diagnosis</topic><topic>Retinal Diseases - genetics</topic><topic>Retinal Diseases - metabolism</topic><topic>Retinal Disorders</topic><topic>Therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Wang, Cong</creatorcontrib><creatorcontrib>Zhang, Shengjuan</creatorcontrib><creatorcontrib>Fu, Zhongjie</creatorcontrib><creatorcontrib>Jiao, Xiaodong</creatorcontrib><creatorcontrib>Jin, Zibing</creatorcontrib><creatorcontrib>Hejtmancik, J. Fielding</creatorcontrib><creatorcontrib>Miao, Huan</creatorcontrib><creatorcontrib>Qi, Simeng</creatorcontrib><creatorcontrib>Peng, Xiaoyan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Graefe's archive for clinical and experimental ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Qian</au><au>Wang, Cong</au><au>Zhang, Shengjuan</au><au>Fu, Zhongjie</au><au>Jiao, Xiaodong</au><au>Jin, Zibing</au><au>Hejtmancik, J. Fielding</au><au>Miao, Huan</au><au>Qi, Simeng</au><au>Peng, Xiaoyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti’s crystalline dystrophy</atitle><jtitle>Graefe's archive for clinical and experimental ophthalmology</jtitle><stitle>Graefes Arch Clin Exp Ophthalmol</stitle><addtitle>Graefes Arch Clin Exp Ophthalmol</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>262</volume><issue>12</issue><spage>3773</spage><epage>3786</epage><pages>3773-3786</pages><issn>0721-832X</issn><issn>1435-702X</issn><eissn>1435-702X</eissn><abstract>Purpose
Abnormalities in lipid metabolism have been proposed in Bietti’s crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study.
Methods
All participants were genetically confirmed by
CYP4V2
gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites.
Results
Routine lipids profiles showed elevated plasma levels of triglyceride (
P
= 0.043) and low-density lipoprotein cholesterol (
P
= 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6,
P
= 0.00068) and eicosapentaenoic acid (EPA, 20:5,
P
= 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4,
P
< 0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (
P
< 0.0001) between BCD patients and controls. Genotypes of
CYP4V2
, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites including 5-HETE, 5-HEPE, 12-HEPE and LTB4.
Conclusions
BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream metabolites via the COX and LOX pathways, suggesting that these might be implicated in BCD pathogenesis and could serve as biomarkers and therapeutic targets of the disease.
Key messages
What is known
BCD is a vision-threatening hereditary disease the causative gene of which is
CYP4V2
.
Abnormalities in lipid metabolism have been proposed and demonstrated previously in BCD studies.
The detailed pathogenesis remains unclear and controversial.
What is new
We observed prominent lipidomic alterations in the circulation when compared with age, gender, and bodymass index (BMI)-matched healthy controls.
BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA).
Remarkable changes were observed in the downstream metabolites of the LCPUFA via the COX and LOX pathways.
Genotypes of
CYP4V2
, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38963460</pmid><doi>10.1007/s00417-024-06554-2</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-4275-6856</orcidid><orcidid>https://orcid.org/0000-0003-0613-9591</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0721-832X |
| ispartof | Graefe's archive for clinical and experimental ophthalmology, 2024-12, Vol.262 (12), p.3773-3786 |
| issn | 0721-832X 1435-702X 1435-702X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3075704150 |
| source | Springer Nature |
| subjects | Adult Arachidonic acid Atrophy Biomarkers Biomarkers - blood Biomarkers - metabolism Case-Control Studies Cholesterol Corneal Dystrophies, Hereditary - blood Corneal Dystrophies, Hereditary - diagnosis Corneal Dystrophies, Hereditary - genetics Corneal Dystrophies, Hereditary - metabolism Cytochrome P450 Family 4 - genetics Cytochrome P450 Family 4 - metabolism DNA - genetics Docosahexaenoic acid Dystrophy Eicosapentaenoic acid Female Genotypes Hereditary diseases Humans Lipid metabolism Lipid Metabolism - physiology Lipidomics - methods Lipids Lipoxygenase Male Medicine Medicine & Public Health Metabolism Metabolites Middle Aged Mutation Ophthalmology Oxylipins - blood Pathogenesis Plasma Plasma levels Polyunsaturated fatty acids Prostaglandin E2 Prostaglandin endoperoxide synthase Retinal Diseases - blood Retinal Diseases - diagnosis Retinal Diseases - genetics Retinal Diseases - metabolism Retinal Disorders Therapeutic targets |
| title | Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti’s crystalline dystrophy |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T06%3A10%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Targeted%20lipidomics%20uncovers%20oxylipin%20perturbations%20and%20potential%20circulation%20biomarkers%20in%20Bietti%E2%80%99s%20crystalline%20dystrophy&rft.jtitle=Graefe's%20archive%20for%20clinical%20and%20experimental%20ophthalmology&rft.au=Li,%20Qian&rft.date=2024-12-01&rft.volume=262&rft.issue=12&rft.spage=3773&rft.epage=3786&rft.pages=3773-3786&rft.issn=0721-832X&rft.eissn=1435-702X&rft_id=info:doi/10.1007/s00417-024-06554-2&rft_dat=%3Cproquest_cross%3E3134402672%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c256t-86735fdac5bcd722ec373f41d8c1ed27d2a4095debe52dd31faaf356ac97a6213%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3134402672&rft_id=info:pmid/38963460&rfr_iscdi=true |