Researchers discover key mechanism of IOP regulation suggesting novel treatment approaches for glaucoma
The microRNA(miR)-17-92 cluster is known to play an important role in cell signaling, but its specific functions in the eye are not well understood. The researchers’ focus lies in gaining insights into the mechanisms of miR-17-92 cluster members and their effects on IOP.
(Image Credit: AdobeStock/auremar)
Researchers at the Hong Kong Polytechnic University have uncovered the mechanism of IOP regulation, paving the way for novel treatment approaches for glaucoma, with the goal of ultimately preventing vision loss from this disease.
According to a Hong Kong Polytechnic University news release, glaucoma is one of the leading causes of visual impairment and blindness. In its early stages, symptoms may not be present and those that are less obvious can be overlooked. By the time patients notice changes in their vision, the condition is usually severe.
Samantha Shan, PhD, BSc, MPhil, a research assistant professor with the School of Optometry of The Hong Kong Polytechnic University (PolyU), led the research project.
When it comes to glaucoma, the researchers noted that current drugs have limitations, generally only slowing disease progression rather than halting it completely. Drugs may also have suboptimal tolerability and their efficacy diminishes over time.
The microRNA (miR)-17-92 cluster is known to play an important role in cell signaling, but its specific functions in the eye are not well understood. Shan and her team’s research focus lies in gaining insights into the mechanisms of miR-17-92 cluster members and their effects on IOP. The research team has identified thrombospondin-1 (TSP-1) as a protein that reduces the outflow of aqueous humor and increases IOP.
At the same time, the researchers mimicked 3 members of the miR-17-92 cluster in human trabecular meshwork (hTM) cells which are responsible for draining aqueous humor within the eye. It showed that the expression of TSP-1 was repressed, resulting in an approximately 73% increase in the outflow of aqueous humor in mice.1
The research team has investigated the mechanisms of miR-17-92 cluster on intraocular pressure and performed immunostaining on TSP-1. (Image credit: Research and Innovation Office, The Hong Kong Polytechnic University)
Shan’s team has recently been recognized with a 2024 Shaffer Research Grant from the Glaucoma Research Foundation to further explore the effects of miR-17-92 members in IOP regulation. Going forward, the team will look at the direct interaction between specific miRNAs and TSP-1 by blocking the potential target sites of the 3 miRNAs in TSP-1 in hTM cells. The researchers will also look at the functional consequences of modulating this pathway on aqueous humor outflow and IOP regulation in vivo. This would be achieved by utilizing intravitreal injections of a TSP-1 target-specific blocker or miRNA mimics in mouse eyes.1
“Genomic and proteomic approaches play a crucial role in understanding the genetic and molecular mechanisms underlying diseases such as glaucoma,” Shan said. “In the context of glaucoma treatment, these approaches can help identify potential biomarkers, therapeutic targets and personalized treatment options, with far-reaching implications.”
Moreover, Shan pointed out that the grant also demonstrates PolyU’s excellence as hosting one of the top eye research centers in the world.
“It encourages me and my team to continue to make significant strides in glaucoma research and contribute to the better care of glaucoma patients,” she said.
For more than a decade, Shan has been involved in molecular research, focusing on the mechanism of aqueous humor formation, outflow facility and IOP regulation, microRNAs on outflow facility, DNA methylation of potential candidates on outflow facility and IOP regulation.
According to the Hong Kong Polytechnic University news release, Shan has received support from the Hong Kong SAR Government’s Health and Medical Research Fund for 2 projects as a principal investigator.1
The focus of the project is to discover gene editing methods for treating glaucoma and unravel the role of epigenetic regulation in glaucoma respectively. Shan has also served as a co-investigator on other diverse research topics and has secured notable research funding, including the Research Grants Council’s General Research Fund.
Reference:
PolyU scholar discovers key mechanism of intraocular pressure regulation suggesting novel treatment approaches for glaucoma. EurekAlert! Accessed July 29, 2024. https://www.eurekalert.org/news-releases/1052691
