# Stage-Associated Cellular and Molecular Signatures in Diabetic Retinopathy Identified Through Integrated Bulk and Single-Cell Transcriptomic Analysis

## TL;DR

This study identifies cell and gene changes in different stages of diabetic retinopathy using combined transcriptomic data, offering insights into disease progression.

## Contribution

The study integrates bulk and single-cell transcriptomic data to reveal stage-specific cellular and molecular signatures in diabetic retinopathy.

## Key findings

- Photoreceptors show ribosomal pathway changes in the NDR stage of DR.
- Endothelial and pericyte cells exhibit transcriptional changes and LAMININ signaling in NPDR.
- ANGPTL signaling is altered in neural and glial cells during PDR.

## Abstract

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and can lead to severe visual impairment. Based on disease severity, DR is classified into no clinically apparent diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Although nearly all retinal cell types are involved in DR progression, the dominant cell populations and their pathophysiological changes at each stage remain unclear. By integrating bulk and single-cell transcriptomic data from human and mouse retinas, this study revealed the following: (1) In the NDR stage, photoreceptors exhibit significant changes in ribosomal pathways. (2) In the NPDR stage, endothelial cells and pericytes show marked transcriptional alterations, accompanied by enhanced LAMININ signaling in cell-cell communication. (3) At the PDR stage, neural and glial cells are extensively involved in disease progression, with notable changes in ANGPTL signaling. Additionally, this study observed DR-specific subtypes of endothelial cells and pericytes and potentially identifies gene signatures in macroglia cells that correlate with disease duration. The altered expression of several key genes in early diabetic retina was confirmed by qPCR. These findings may offer a comprehensive view of the cellular and molecular landscape underlying DR and may suggest potential targets.