July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
ILB reduces trabecular meshwork scarring, IOP and retinal ganglion cell death in a rat model of primary open angle glaucoma
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, Viken, 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), TikoMed AB (F); Ann Logan, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4723. doi:
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      Lisa J Hill, Hannah Botfield, Lars Bruce, Ann Logan; ILB reduces trabecular meshwork scarring, IOP and retinal ganglion cell death in a rat model of primary open angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4723.

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

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Abstract

Purpose : Raised IOP is a major risk factor for developing Primary Open Angle Glaucoma. Reduced outflow of aqueous humour secondary to fibrosis in the Trabecular Meshwork (TM) elevates IOP causing Retinal Ganglion Cell (RGC) death and blindness. ILB, a specific type of dextran sulfate, owned and patented by TikoMed AB, has anti-fibrogenic properties that reverses established scarring by modulating fibrogenic growth factor activity and activating proteases that lyse collagen, fibronectin and laminin. Hence, we suggest that ILB is an alternative treatment strategy for established POAG that has the potential to prevent progressive visual loss, by lowering IOP through the dissolution of TM fibrosis thereby protecting RGC from progressive death.

Methods : Sprague Dawley rats received twice weekly intracameral injections of 5ng/μl TGF-β (to induce TM fibrosis and raise IOP for 28d). At 14d, rats were administered either 15mg/kg of ILB (n=7) or Saline (vehicle control; n=5) by daily by sub-cutaneous injections. IOP were measured twice weekly and eyes were harvested at 28d for immunohistological analysis of TM fibrosis. RGC survival was determined by immunoreactivity to BRN3a. Anterior segment imaging and OCT at 28d were performed to examine the angle and thickness of the retinal nerve fibre layer respectively.

Results : TGFβ led to significant increases in IOP by 14d in all rats. Rats that received ILB showed significant reductions in IOP after 14d of treatment (14±0.6mmHg at 14d to 11±0.2mmHg at 28d), compared to vehicle treated rats which remained high. This reduction in IOP was correlated with a significant increase in RGC survival compared to vehicle treated rats. In addition, the RNFL remained significantly thicker in ILB treated rats compared to vehicle at 28d. By 28d, ILB treated rats had significantly reduced established TM fibrosis, with IOP lowered to baseline levels and preserved RGC viability.

Conclusions : ILB treatment led to a rapid restoration of normal IOP in glaucomatous eyes which was associated with preservation of RGC after 14d of ILB treatment. The fall in IOP probably resulted from dissolution of established TM scarring shown in the ILB treated rats. Given that current glaucoma treatments do not address the underlying pathology, a treatment that reverses the glaucomatous pathology would be highly valuable.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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