Scientists at the University of Birmingham, UK, have shown that novel low-molecular-weight dextran-sulphate, ILB®, could play a new role in the treatment of open-angle glaucoma (OAG), a neurodegenerative disease that affects more on 70 million people worldwide and causing irreversible change. blindness.
OAG develops slowly over several years. Excessive matrix deposition (fibrosis) within the primary drainage site of the retina can lead to increased intraocular pressure (IOP), causing damage to the optic nerve.1
The research, reported in Regenerative Medicine npj, has shown that ILB can lower intracellular matrix deposition and IOP in a preclinical model used to identify these aspects of human glaucoma, paving the way for the development of new anti-fibrotic therapies for the disease.
OAG is a complex disease and it has been difficult to develop an effective treatment to target the biochemical pathways involved. Conventional treatments usually work by reducing fluid production in the eye, not the underlying causes, and even the new therapies have shown limited success in the clinic.2
Birmingham scientists focused on an inflammatory pathway that is common to several diseases, and included Transforming Growth Factor β (TGFβ), a signaling molecule that communicates between cells and orchestrates both inflammation and fibrosis . The role of TGFβ in OAG is well known, with patients showing higher levels of humor and laboratory studies showing that elevated TGFβ intravenously within the eye can lead to fibrosis.3,4.
The scientists found that ILB has multifactorial functions across many genes that disrupt inflammatory and fibrotic cellular processes. When they applied the work to a preclinical experimental model of glaucoma, they found that daily injections of ILB were significant (p
Clinicians working in ophthalmology usually prefer local treatment delivered systematically, because it is a safer method of administration that is more suitable for patients.
Dr. Hill is leading a project to develop a conventional alternative to avoid the need for injection. She is working closely on this with Mr Imran Masood, a consultant ophthalmic surgeon at Sandwell and West Birmingham NHS Trust and Professor Liam Grover, a biomaterials expert from the University’s Institute of Healthcare Technologies, to assess the using a thin liquid gel for the resolution of glaucoma.
The thinning liquid gel was developed for use as eye drops that are kept for an extended period of time after administration, and patents have been filed for use both alone, and in conjunction with medical- other medicine.5 Previous studies have shown that the liquid gel reduces corneal scarring when applied topically, and is an effective behavioral molecule for other medical treatments.6
###
References:
- 1. Tektas, OY & Lutjen-Drecoll, E. Structural changes of the trabecular meshwork in different types of glaucoma. Experimental eye research, 88 (4), 769-75 (2009).
2. Friedman, SL, Sheppard, D., Duffield, JS & Violette, S. Therapy for fibrotic diseases: Near the starting line. Science Translational Medicine 5 (167), 167sr1-sr1 (2013).
3. Fuchshofer, R. & Tamm, ER The role of TGF-beta in the pathogenesis of open-angle glaucoma. Cell and tissue research, 347 (1), 279-90 (2012).
4. Kim, KS, Lee, BH & Kim, IS Measurement of fibronectin concentrations in human aqueous humor. Korean Journal of Ophthalmology, 6 (1), 1-5 (1992).
5. Patent numbers: WO / 2020/115510; WO / 2020/115508; GB2008919.9
6. Hill et al. Stable release of decorin to the surface of the eye enables scarce corneal regeneration. Regenerative Medicine npj. 3, 1-12 (2018).
Disclaimer: AAAS and EurekAlert! they are not responsible for the accuracy of press releases posted to EurekAlert! by sending institutions or for using any information through the EurekAlert system.