Targeting retinal ganglion cell recovery

Developers

J G Crowston, E T Fahy, L Fry, S Petrou, V Chrysostomou, etc.

Description of the technology

The development of this technology was based on the results of studies, demonstrated that retinal ganglion cells at least in the earlier stages of glaucoma have the capacity to recover function following periods of functional loss. Vision loss in glaucoma results from the progressive loss of retinal ganglion cells and it is generally considered irreversible. However, actually inner retina has plasticity with the potential for vision recovery in glaucoma patients in response to intraocular pressure lowering. This improvement in visual function is short-term.

In the model of recoverable retinal ganglion cell function in the mouse eye, one eye of an anesthetized mouse was subject to a single intraocular pressure lowering of 50 mm Hg lasting 30 min. Retinal function was monitored before, and at 7 and 28 days post injury using the full-field electroretinogram. The inner retinal (mainly, functions of retinal ganglion cells) function were monitored by measuring the photopic negative response amplitude of the electroretinogram in lightadapted eyes or the positive scotopic threshold response in dark-adapted eyes. It was found that mouse age had a major impact on the rate of functional recovery. The latter decreases with age.

The capacity for recovery of retinal ganglion cell function in this method has been boosted by interventions such as diet restriction and exercise. The intermittent fasting and exercise, two interventions that slow biological ageing, improved retinal ganglion cell recovery in older animals, such that exercised 12-month-old animals exhibited full functional recovery by 7 days. In the case of exercise, improved recovery occurred even when exercise was initiated 24 h after intraocular pressure injury. The retina of exercised animals also manifested reduced astrocytosis, reduced microglial activation, and reduced complement factor C1q activation following injury, and this was associated with the preservation of synapse density in the inner plexiform layer of the retina.

Practical application

The diet restriction and exercise are well-known interventions that slow biological ageing, however in this technology they have been successfully used for specific recovery of retinal ganglion cell function.

The method determines the role of retinal ganglion cells in glaucoma treatment. The proportion of nonfunctioning retinal ganglion cells may ultimately determine the degree by which the electroretinogram and other parameters of visual function can be improved in response to intraocular pressure lowering.

Laboratories

• Royal Victorian Eye and Ear Hospital, Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria (Australia)
• Centre for Eye Research Australia and Department of Surgery, University of Melbourne Royal Victorian Eye and Ear Hospital, Melbourne (Australia)

Links

Publications

• Crowston J.G., et al. «Targeting retinal ganglion cell recovery." Eye (Lond). 2017 Jan 6. [Epub ahead of print].
• Chrysostomou, v. et al. «Exercise reverses age-related vulnerability of the retina to injury by preventing complement-mediated synapse elimination via a BDNFdependent pathway." Aging Cell 2016. 9 September 2016. [Epub ahead of print].
• Chrysostomou, v. et al. «Forced exercise protects the aged optic nerve against intraocular pressure injury." 35 Neurobiol Aging, (2014): 1722–1725.