Aging & Longevity

MicroRNA profiling of filtering and non-filtering regions of human trabecular meshwork: changes with ageing and in glaucoma.

TL;DR

MicroRNA profiling of filtering and non-filtering regions of human trabecular meshwork identified differentially expressed miRNAs in the non-filtering region that exhibited age-associated decline and were reduced in glaucomatous donor tissue, suggesting roles in trabecular meshwork stem cell regulation.

Key Findings

Thirty-one miRNAs were significantly up-regulated and three were down-regulated in the non-filtering (NF) region compared to the filtering (F) region of the human trabecular meshwork.

  • Profiling was performed using the nanoString nCounter platform on human donor trabecular meshwork tissue
  • The threshold for differential expression was a fold change ≥ ±1.2
  • The NF region is the location of trabecular meshwork stem cells (TMSCs)

Specific miRNAs showing increased expression in the NF region were miR-24-3p, miR-107, miR-34a-5p, and miR-184, while miR-376a-3p, miR-145-5p, and miR-22-3p showed decreased expression in the NF region.

  • These differentially expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR)
  • Validation was performed in age-stratified donor tissues grouped into three categories: 0–30, 30–60, and >60 years
  • The expression patterns highlighted their probable role in stem cell regulation

An age-related decline in miR-107, miR-184, and miR-34a-5p expression was observed in the NF region of the trabecular meshwork.

  • The decline was observed across age-stratified donor tissue groups (0–30, 30–60, and >60 years)
  • These miRNAs were among those up-regulated in the NF region relative to the filtering region
  • The age-associated decline is consistent with the previously reported decrease in trabecular meshwork stem cells (TMSCs) with ageing

In glaucomatous (POAG) donor tissues, miR-145-5p, miR-22-3p, and miR-376a-3p showed up-regulation in the trabecular meshwork.

  • Glaucomatous tissues were obtained as FFPE (formalin-fixed paraffin-embedded) sections from POAG donors
  • These three miRNAs were normally down-regulated in the NF region compared to the filtering region in non-glaucomatous donors
  • Up-regulation of these miRNAs was observed even in young glaucomatous donors
  • miR-107, miR-184, and miR-34a-5p (normally up-regulated in NF region) were reduced in young glaucomatous donor tissue

Bioinformatic analysis indicated that the validated differentially expressed miRNAs are involved in stem cell-related signalling pathways.

  • Pathway analysis was performed using Shiny GO 0.82 for functional enrichment analysis
  • miRNA targets were identified using miRTarBase
  • Pathways implicated included Wnt, HIF, PI3K-AKT, and MAPK signalling
  • These pathways are associated with stem cell regulation, consistent with the known biology of TMSCs in the NF region

Adult trabecular meshwork stem cells (TMSCs) present in the non-filtering region decrease with ageing and are significantly reduced in primary open angle glaucoma (POAG).

  • This finding is cited as background context motivating the study
  • The reduction in TMSCs with ageing and in POAG is used to frame the miRNA profiling investigation
  • The study sought to identify miRNAs that may regulate TMSC maintenance in the NF region

What This Means

The eye's drainage system, called the trabecular meshwork (TM), contains a special population of stem cells located in a specific area called the non-filtering (NF) region. These stem cells help maintain and repair the drainage tissue, and their loss is associated with ageing and glaucoma. This research suggests that small RNA molecules called microRNAs (miRNAs) play an important role in controlling the behavior of these stem cells. The researchers identified 34 miRNAs that are expressed differently between the stem cell-containing region and the rest of the trabecular meshwork, with 31 being more active and 3 less active in the stem cell region. This research suggests that seven specific miRNAs are particularly important: miR-24-3p, miR-107, miR-34a-5p, and miR-184 are more active in the stem cell region, while miR-376a-3p, miR-145-5p, and miR-22-3p are less active there. Importantly, the miRNAs that are normally more active in the stem cell region (miR-107, miR-184, and miR-34a-5p) showed a decline with ageing, mirroring the known reduction in stem cells over time. In people with glaucoma, the miRNAs that are normally less active in the stem cell region were found to be abnormally elevated, even in younger donors with the disease. This research suggests that the abnormal miRNA patterns seen with ageing and glaucoma may contribute to the decline of trabecular meshwork stem cells, potentially impairing the eye's ability to maintain proper drainage and pressure. The miRNAs identified appear to regulate key biological pathways involved in stem cell maintenance, including Wnt, PI3K-AKT, and MAPK signalling. The authors note that further laboratory experiments directly manipulating these miRNAs are needed to confirm their specific roles, but the findings open potential avenues for understanding how trabecular meshwork deterioration occurs in ageing and glaucoma.

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Citation

Nair S, Devarajan B, Vanniarajan A, Ravichandran N, Ramaswamy G, Bhat V, et al.. (2026). MicroRNA profiling of filtering and non-filtering regions of human trabecular meshwork: changes with ageing and in glaucoma.. Molecular biology reports. https://doi.org/10.1007/s11033-026-12667-0