Tears may hold the key to diagnosis and treatment

PILOT STUDY ON BIOMARKERS IN TEARS AND CELLS SHEDS NEW LIGHT ON USHER SYNDROME TYPE 1B

Can tears provide critical information for improving diagnostics and monitoring future treatments for USH1B patients? This was the question posed by Dr. Irene Vázquez Domínguez when she began her study, “Investigating the exosome content as a novel marker for Usher syndrome 1B”, at Radboudumc in 2023. The pilot study, funded by Stichting Ushersyndroom with co-funding from Usher Syndrome Ireland, has recently concluded, yielding surprising results. 

The study’s focus
This pilot study explored whether extracellular vesicles (EVs)—tiny carriers of cellular messages—found in tears and the culture media of retinal pigment epithelial (RPE) cells could serve as biomarkers. Focusing on Usher syndrome type 1B, a condition caused by mutations in the MYO7A gene, the research aimed to uncover disease mechanisms and pave the way for potential therapeutic breakthroughs. Read also ‘Tears as a sourche of information?’

Important insights
This research has provided important insights into how genetic errors in MYO7A can affect the body, and how small messages in cells and tears play a role in Usher syndrome. In particular, the unique RNA profiles in tears and RPE cells offer opportunities to better understand the disease and perhaps diagnose or treat it in the future.

Although the research has already provided promising insights, the researcher emphasizes that larger cohorts are needed to validate the results.

Key findings

  • MYO7A mutations: Mutations in the MYO7A gene, primarily located in the MyTH4 domain, were identified. This domain plays a vital role in the protein’s function.
  • RPE cells (cells in the retina that support photoreceptors) produce EVs that carry important messages. These packets are only produced on one side of the cell, the side facing the retina (apical).
  • Normal cell development: Despite MYO7A mutations, RPE cells developed normally, and protein localization remained intact.
  • Small RNA differences: Small non-coding RNAs (sncRNAs) in EVs differed significantly between patients with Usher syndrome and healthy individuals, indicating their potential as diagnostic markers.
  • Tears as a source: EVs in tears contained a broader range of sncRNAs than those from lab-cultured RPE cells. Tears may therefore serve as a more comprehensive source of diagnostic information.

These insights highlight the potential of sncRNAs as both biomarkers and therapeutic targets in retinal diseases like Usher syndrome.

Implications for patients
Validating tears as a source of biomarkers opens new possibilities for diagnostics and treatment. By understanding molecular mechanisms and specific sncRNAs, researchers can develop therapies aimed at restoring normal retinal function.

International collaboration and future research
The project was conducted at Radboudumc, with Dr. Irene Vázquez Domínguez transitioning to a postdoctoral position at the Universitary Hospital Ramón and Cajal, Spain, in mid-2024. The study has secured follow-up funding through the Marie Sklodowska-Curie ARISTOS fellowship program coordinated by the CIBER in Spain. Over the next three years, the research will delve deeper into RNA molecules and EVs in Usher syndrome type 1B as well as in other inherited retinal diseases. This collaboration underscores the importance of international efforts to advance both fundamental research and clinical applications.


WHAT ARE RPE CELLS?
Retinal Pigment Epithelial (RPE) cells are essential cells in the retina that support photoreceptors, the light-sensitive cells responsible for vision. Damage or dysfunction in RPE cells can lead to severe eye diseases, including Retinitis Pigmentosa (RP): A genetic condition where photoreceptors and RPE cells degenerate. 

RPE Cells in research and therapy
RPE cells play a crucial role in studies targeting retinal diseases: 

* Stem Cell Therapy: RPE cells can be grown from stem cells and transplanted to replace damaged cells. 
* Gene Therapy: Efforts focus on correcting genetic defects in RPE cells. 
* Drug Development: RPE cells are studied as targets for drugs to treat degenerative diseases. 

WHAT ARE EVs?
Extracellular vesicles (EVs) are tiny, membrane-bound structures secreted by cells. They are crucial for cellular communication and molecular transport. 

EVs act as “packets” carrying signals or molecules to other cells, playing a vital role in processes like tissue repair, immune responses, and maintaining cellular health. 

In RPE cells, EVs often contain molecules essential for photoreceptor health and the visual cycle. 

WHAT ARE sncRNAs?
Small non-coding RNAs (sncRNAs) are tiny RNA molecules that do not encode proteins but play important regulatory roles in cells. 

In the context of Usher syndrome, specific sncRNAs in EVs may: 

        1. Protect photoreceptors from degeneration.
        2. Regulate inflammation in the retina.
        3. Support repair processes in retinal cells.

By: Ivonne Bressers
Date: 27-01-2025

Support scientific research
This study demonstrates the power of collaboration and innovative research. Stichting Ushersyndroom remains committed to funding projects that bring hope to those with Usher syndrome.

Together, we can build a future without boundaries, without limits, and without Usher syndrome.