Single-Cell Insights Into Diabetic Retinopathy Mechanisms

NCT06497608 | Not Yet Recruiting

• 1 other identifier: 2023321
• Study Type: observational
• Target: 66
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Diabetic Retinopathy

Outcome Measures

Primary Outcomes (1)

• Single cell sequencing result

  Single cell RNA and ATAC sequencing of human retinas

  1 month

Secondary Outcomes (1)

• Validation experiment result

  1 month

Study Arms (4)

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients who visit the Department of Ophthalmology at Shanghai General Hospital and meet the inclusion and exclusion criteria of this study.

You may qualify if:

• For the single-cell sequencing group: Patients with advanced proliferative diabetic retinopathy (PDR) resulting in blindness or ocular atrophy, who voluntarily opt for enucleation and ocular prosthesis implantation surgery, and have no systemic or local contraindications to surgery. For the validation group: patients with severe PDR lesions requiring vitrectomy, and who also have no systemic or local contraindications to surgery.
• Patients who voluntarily agree to participate in this clinical trial and sign the informed consent form.

You may not qualify if:

• Patients with severe systemic diseases such as autoimmune diseases or cancer

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Related Publications (5)

• 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.

  PMID: 35061025 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.

  PMID: 33674409 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.

  PMID: 32734440 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.

  PMID: 28212749 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.

  PMID: 20580421 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Diabetic Retinopathy

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Zhi Zheng, Prof.

  Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yujie Wang, Dr.

CONTACT

0061-422510790; yujiwang11@student.unimelb.edu.au

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: July 4, 2024
• First Posted: July 12, 2024
• Study Start: July 1, 2024
• Primary Completion: September 1, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 12, 2024

Record last verified: 2024-07