R and L Lowe Bequest Grant
Investigator: Dr Glyn Chidlow
Co-Investigator: Dr Andreas Ebneter
Aim: Retinal vein occlusions are common disorders which occur when blood clots block veins within
the retina.The aims of this project are to establish translatable rodent models of ischemic retinal vein occlusion (iRVO) and to assess the therapeutic value of a novel calpain antagonist.
Methods: Venous supply to a proportion of the retina is blocked by targeting two to three major veins via laser treatment.The extent of ischemic injury and nerve cell survival are assessed by functional and histopathological methodologies.Some eyes receive a single injection of the calpain antagonist to assess whether it aids recovery.
Key Results: The investigators have successfully established rat and mouse models of iRVO. Following venous blockage, spatially-defined areas of low oxygen availability (hypoxia) are evident within the retina throughout the first 24hours, with decreasing hypoxia observed in subsequent days.These hypoxic regions are associated with nerve cell stress and death, together with activation and proliferation of the supporting glial cells.We are presently conducting experiments with the novel drug in order to ascertain its potential clinical effectiveness.
Conclusion: We have successfully developed rodent models of iRVO that recapitulate the disease pathology that occurs in patients with ischemic vein occlusions.These exciting results have allowed us to commence testing of a novel therapy for the disease.
Implications for Clinical Practice/Science and Future Research: There is currently no effective treatment for individuals with iRVO.The development of valid preclinical models of the disease is a vitally important step for testing new therapeutic strategies.The novel drug being evaluated in this project has the potential for rapid clinical translation at the time of diagnosis.
Publications arising from this work: Characterisation of a Rat Model of Branch Retinal Vein Occlusion. A thesis submitted in partial fulfilment of the Honours Degree of Bachelor of Health and Medical Sciences, University of Adelaide. Luke Rezk. November 2021.
Images: Characterisation of a Rat Model of Branch Retinal Vein Occlusion. Luke Rezk, Robert Casson, Glyn Chidlow. Florey Undergraduate Conference, University of Adelaide. October 2021.