# Serum RNA Profile Reflects Fluid Status and Atrophic Retinal Changes in Neovascular Age-Related Macular Degeneration

**Authors:** Hanna Heloterä, Joanna Kostanek, Mikko Liukkonen, Leea Siintamo, Suvi Linna-Kuosmanen, Cezary Watala, Janusz Blasiak, Kai Kaarniranta

PMC · DOI: 10.3390/ijms26104852 · International Journal of Molecular Sciences · 2025-05-19

## TL;DR

This study shows that RNA in blood can reflect retinal changes in a form of macular degeneration, offering new insights for diagnosis and treatment.

## Contribution

The study identifies a serum RNA profile linked to retinal changes in neovascular AMD, revealing a novel pathway for AMD research.

## Key findings

- Serum RNA profiles differ between neovascular AMD patients and healthy controls.
- RNA profiles correlate with retinal fluid status and atrophic changes in AMD patients.
- Thioredoxin-related transmembrane protein 4 (TMX4) is differentially expressed in AMD patients.

## Abstract

The increasing prevalence of age-related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. Growing patient numbers create a challenge for the healthcare system. Understanding the mechanisms of AMD pathogenesis will aid in early, personalized, and efficient intervention, helping to mitigate this issue. Current diagnostic methods rely on optical coherence tomography and angiography imaging, which identify existing damages, but do not provide information on the mechanisms behind them. In the present work, we demonstrate a difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments as well as atrophic changes of the retina. We followed two independent ways to control false positive leads, and when these approaches were combined, thioredoxin-related transmembrane protein 4 (TMX4) was observed to be differentially expressed by both approaches. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD.

## Linked entities

- **Genes:** TMX4 (thioredoxin related transmembrane protein 4) [NCBI Gene 56255]
- **Diseases:** age-related macular degeneration (MONDO:0005150)

## Full-text entities

- **Genes:** TMX4 (thioredoxin related transmembrane protein 4) [NCBI Gene 56255] {aka DJ971N18.2, PDIA14, TXNDC13}
- **Diseases:** AMD (MESH:D008268), atrophic changes of the retina (MESH:D019572), loss of central vision (MESH:D014786)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12112293/full.md

## References

109 references — full list in the complete paper: https://tomesphere.com/paper/PMC12112293/full.md

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Source: https://tomesphere.com/paper/PMC12112293