Martin Schicht , Jessica Farger , Saskia Wedel , Marco Sisignano , Klaus Scholich , Gerd Geisslinger , Natarajan Perumal , Franz H. Grus , Swati Singh , Afsun Sahin , Friedrich Paulsen , Elke Lütjen-Drecoll
{"title":"链脲佐菌素诱发糖尿病和糖尿病多发性神经病变小鼠眼表的变化","authors":"Martin Schicht , Jessica Farger , Saskia Wedel , Marco Sisignano , Klaus Scholich , Gerd Geisslinger , Natarajan Perumal , Franz H. Grus , Swati Singh , Afsun Sahin , Friedrich Paulsen , Elke Lütjen-Drecoll","doi":"10.1016/j.jtos.2023.12.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p><span>Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral </span>polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear.</p></div><div><h3>Methods</h3><p><span>In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, </span>dorsal root<span> and trigeminal ganglia<span><span> with the changes in the ocular surface, including tear </span>proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.</span></span></p></div><div><h3>Results</h3><p>The lacrimal gland<span><span>, conjunctival goblet cells and cornea showed morphological changes along with alterations in </span>tear proteins<span><span><span> without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of </span>Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and </span>Pigr<span> in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia<span><span> neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases<span> and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating </span></span>chemokines.</span></span></span></span></p></div><div><h3>Conclusion</h3><p>The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment<span> could delay or even prevent the ocular complications of DM such as DED and PN.</span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"31 ","pages":"Pages 43-55"},"PeriodicalIF":5.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy\",\"authors\":\"Martin Schicht , Jessica Farger , Saskia Wedel , Marco Sisignano , Klaus Scholich , Gerd Geisslinger , Natarajan Perumal , Franz H. Grus , Swati Singh , Afsun Sahin , Friedrich Paulsen , Elke Lütjen-Drecoll\",\"doi\":\"10.1016/j.jtos.2023.12.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p><span>Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral </span>polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear.</p></div><div><h3>Methods</h3><p><span>In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, </span>dorsal root<span> and trigeminal ganglia<span><span> with the changes in the ocular surface, including tear </span>proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.</span></span></p></div><div><h3>Results</h3><p>The lacrimal gland<span><span>, conjunctival goblet cells and cornea showed morphological changes along with alterations in </span>tear proteins<span><span><span> without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of </span>Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and </span>Pigr<span> in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia<span><span> neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases<span> and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating </span></span>chemokines.</span></span></span></span></p></div><div><h3>Conclusion</h3><p>The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment<span> could delay or even prevent the ocular complications of DM such as DED and PN.</span></p></div>\",\"PeriodicalId\":54691,\"journal\":{\"name\":\"Ocular Surface\",\"volume\":\"31 \",\"pages\":\"Pages 43-55\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ocular Surface\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S154201242300157X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ocular Surface","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S154201242300157X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy
Purpose
Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear.
Methods
In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.
Results
The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines.
Conclusion
The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.
期刊介绍：
The Ocular Surface, a quarterly, a peer-reviewed journal, is an authoritative resource that integrates and interprets major findings in diverse fields related to the ocular surface, including ophthalmology, optometry, genetics, molecular biology, pharmacology, immunology, infectious disease, and epidemiology. Its critical review articles cover the most current knowledge on medical and surgical management of ocular surface pathology, new understandings of ocular surface physiology, the meaning of recent discoveries on how the ocular surface responds to injury and disease, and updates on drug and device development. The journal also publishes select original research reports and articles describing cutting-edge techniques and technology in the field.
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