July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
A newly formulated low-weight dextran sulphate, ILB, reduces inflammation and fibrosis in pre-clinical models of inflammation and scarring
Author Affiliations & Notes
  • Lisa J Hill
    Neurobiology, University of Birmingham, Edgbaston, ENGLAND, United Kingdom
  • Hannah Botfield
    Neurobiology, University of Birmingham, Edgbaston, ENGLAND, United Kingdom
  • Lars Bruce
    TikoMed AB, Sweden
  • Ann Logan
    Neurobiology, University of Birmingham, Edgbaston, ENGLAND, United Kingdom
  • Footnotes
    Commercial Relationships   Lisa Hill, None; Hannah Botfield, None; Lars Bruce, Tikomed AB (P); Ann Logan, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3793. doi:
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      Lisa J Hill, Hannah Botfield, Lars Bruce, Ann Logan; A newly formulated low-weight dextran sulphate, ILB, reduces inflammation and fibrosis in pre-clinical models of inflammation and scarring. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3793.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : In glaucoma, reduced outflow of aqueous humour, secondary to fibrosis in the Trabecular Meshwork (TM), elevates IOP causing Retinal Ganglion Cell (RGC) death. ILB, a modified dextran sulfate, owned and patented by TikoMed AB, has anti-inflammatory/anti-fibrogenic properties that can modulate inflammation and resolve established fibrosis. The purpose of this study was to investigate the anti-inflammatory mechanisms of ILB in human cell based assays and to demonstrate the efficacy of ILB to reduce established TM fibrosis in rodents.

Methods : Rats received intracameral (IC) injections of TGF-β (to induce TM fibrosis and raise IOP). At 14d, rats were then given 15mg/kg of ILB or 0.9% Saline by daily sub-cutaneous injections. IOP were measured throughout and eyes harvested at 28d for analysis of TM fibrosis levels. RGC counts and OCT were performed at 28d to examine RGC survival and retinal thickness, respectively. The effects of ILB on human cells was investigated using the BioMAP® assay (12 primary human cell culture systems) for modelling inflammation, wound healing and fibrosis.

Results : Ocular-hypertensive rats that received ILB showed significant IOP reductions, lower levels of TM fibrosis and increased RGC survival/RNFL thickness compared to controls. The BioMap assay demonstrated that ILB reduced inflammatory mediators within arterial smooth cells, and promoted wound healing in human dermal fibroblasts, whilst demonstrating no cytotoxicity in any cell type.

Conclusions : ILB treatment led to a rapid and reproducible restoration of normal IOP in glaucomatous eyes in our pre-clinical rodent model. Restoration of normal IOP levels was associated with preservation of RGC in the retina as evidenced by maintained RGC counts and a preservation of RNFL thickness after 14d of ILB. The fall in IOP probably resulted from dissolution of established TM fibrosis as levels of laminin and fibronectin were significantly lower after ILB treatment. We also demonstrated in human cell models that ILB reduces inflammation and promoted wound remodelling with no cytotoxicity apparent in various primary human cell types. We suggest that ILB is an alternative treatment strategy for established POAG by resolving inflammatory responses and preventing/reversing established TM fibrosis, thereby protecting RGC from progressive death and limiting loss of vision.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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