Multiple mutations in greater than 200 different genes have thus far been implicated in causing retinal degeneration (RD) (https://sph.uth.edu/retnet/), while greater than 30 disease genes give rise to inherited optic neuropathies (ON), including glaucoma. The advent of next generation sequencing (NGS) has enabled further characterization of the underlying basis of these disorders in patient cohorts; current data sets suggest that the genetic basis of inherited RD can be identified in approximately 50% of patients. With higher resolution sequencing and a greater number of causative genes identified, this percentage should rise. Nevertheless it is evident that for a substantial proportion of patients it may not be possible to pinpoint the genetic cause of their condition. While gene specific therapies are appropriate for more commonly mutated disease genes (for example, Rho, CHM) and there has been significant success in clinical trials for both LCA and Choroideremia, some ocular disorders are so rare that it may be challenging to progress gene specific therapies towards clinical trial given associated significant costs. Therapies for patients with unidentified mutations or extremely rare conditions cannot be focused towards the primary genetic defect but indeed must be more ‘generic’, for example, targeted towards modulating secondary defects associated with disease pathology, such as provision of neurotrophic factors or anti-oxidants amongst others. Given the clear need for such ‘generic’ therapies, this application is focused on exploring the therapeutic potential of modulating targets involved in oxidative stress, frequently elevated in retinopathies due to diverse genetic mutations, including optic neuropathies as well as RD. Targeting features of disease such as oxidative stress, common to multiple retinal and other neurological disorders, should provide more readily translatable therapeutic opportunities for these debilitating conditions.
