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This study aims to uncover the cellular and molecular mechanisms of diabetic retinopathy through single-cell sequencing to identify new therapeutic targets.
The study will collect retinal tissue samples from 3 patients with advanced proliferative diabetic retinopathy who underwent prosthetic eye implantation and 3 normal cadaver donors. Additionally, aqueous humor, vitreous fluid, and plasma samples from patients with severe diabetic retinopathy requiring surgery and macular hole surgery patients without diabetic retinopathy will be analyzed using ELISA, qPCR, and Western Blot. These experiments will validate sequencing results and explore the pathogenesis of diabetic retinopathy to identify potential treatment targets.
Diabetic retinopathy is the leading cause of blindness among the working population worldwide. However, its pathogenesis is not fully understood, and effective prevention and treatment methods are limited. This study, initiated by Shanghai First People's Hospital, aims to explore the cellular and molecular mechanisms underlying its occurrence through methods such as single-cell sequencing, to identify new intervention targets. This study plans to collect retinal tissue samples from 3 patients each who underwent prosthetic eye implantation due to late-stage proliferative diabetic retinopathy blindness and from 3 normal cadaver donors at the Ophthalmology Department of Shanghai First People's Hospital for single-cell sequencing and bioinformatics analysis. Additionally, samples of aqueous humor, vitreous fluid, and plasma will be collected from 30 patients with severe diabetic retinopathy requiring surgery and from 30 macular hole surgery patients without diabetic retinopathy. These samples will be subjected to experiments such as ELISA, qPCR, and Western Blot to validate sequencing results, investigate the pathogenesis of diabetic retinopathy, and identify potential therapeutic targets.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| scRNA_DR | Patients with proliferative diabetic retinopathy who underwent prosthetic eye implantation. | ||
| scRNA_normal | Body donors without history of diabetic retinopathy | ||
| Validate_DR | Patients with proliferative diabetic retinopathy (PDR) who underwent vitrectomy surgery | ||
| Validate_normal | Patients who underwent vitrectomy surgery for macular hole (MH) and did not have diabetic retinopathy (DR) |
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| Measure | Description | Time Frame |
|---|---|---|
| Single cell sequencing result | Single cell RNA and ATAC sequencing of human retinas | 1 month |
| Measure | Description | Time Frame |
|---|---|---|
| Validation experiment result | Experiments such as ELISA and immunofluorescence staining to validate the result from single cell sequencing | 1 month |
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Inclusion Criteria :
Exclusion Criteria:
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Patients who visit the Department of Ophthalmology at Shanghai General Hospital and meet the inclusion and exclusion criteria of this study.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yujie Wang, Dr. | Contact | 0061-422510790 | yujiwang11@student.unimelb.edu.au |
| Name | Affiliation | Role |
|---|---|---|
| Zhi Zheng, Prof. | Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35061025 | Background | Hu Z, Mao X, Chen M, Wu X, Zhu T, Liu Y, Zhang Z, Fan W, Xie P, Yuan S, Liu Q. Single-Cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy. Diabetes. 2022 Apr 1;71(4):762-773. doi: 10.2337/db21-0551. | |
| 33674409 | Background | Niu T, Fang J, Shi X, Zhao M, Xing X, Wang Y, Zhu S, Liu K. Pathogenesis Study Based on High-Throughput Single-Cell Sequencing Analysis Reveals Novel Transcriptional Landscape and Heterogeneity of Retinal Cells in Type 2 Diabetic Mice. Diabetes. 2021 May;70(5):1185-1197. doi: 10.2337/db20-0839. Epub 2021 Mar 5. |
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Due to the confidentiality policy of the Chinese National Health Council and institutional patient privacy regulations, we have not decided on the plan to share IPD. However, the data are available from the corresponding authors upon request.
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| ID | Term |
|---|---|
| D003930 | Diabetic Retinopathy |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
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We will collect retinal samples from 3 patients with advanced proliferative diabetic retinopathy who underwent prosthetic eye implantation, as well as retinal samples from 3 healthy cadaver donors. Additionally, we will collect aqueous humor, vitreous fluid, and plasma samples from 30 patients undergoing diabetic retinopathy surgery and 30 macular hole surgery patients without diabetic retinopathy.
| 32734440 | Background | Van Hove I, De Groef L, Boeckx B, Modave E, Hu TT, Beets K, Etienne I, Van Bergen T, Lambrechts D, Moons L, Feyen JHM, Porcu M. Single-cell transcriptome analysis of the Akimba mouse retina reveals cell-type-specific insights into the pathobiology of diabetic retinopathy. Diabetologia. 2020 Oct;63(10):2235-2248. doi: 10.1007/s00125-020-05218-0. Epub 2020 Jul 30. |
| 28212749 | Background | Ziegenhain C, Vieth B, Parekh S, Reinius B, Guillaumet-Adkins A, Smets M, Leonhardt H, Heyn H, Hellmann I, Enard W. Comparative Analysis of Single-Cell RNA Sequencing Methods. Mol Cell. 2017 Feb 16;65(4):631-643.e4. doi: 10.1016/j.molcel.2017.01.023. |
| 20580421 | Background | Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010 Jul 10;376(9735):124-36. doi: 10.1016/S0140-6736(09)62124-3. Epub 2010 Jun 26. |
| D002318 |
| Cardiovascular Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |