Retinitis pigmentosa (RP) is a group of inherited diseases that cause blindness 
due to the progressive death of rod and cone photoreceptors in the retina. There 
are currently no effective treatments for RP. Inherited mutations in rhodopsin, 
the light-sensing protein of rod photoreceptor cells, are the most common cause 
of autosomal-dominant RP. The majority of mutations in rhodopsin, including the 
common P23H substitution, lead to protein misfolding, which is a feature in many 
neurodegenerative disorders. Previous studies have shown that upregulating 
molecular chaperone expression can delay disease progression in models of 
neurodegeneration. Here, we have explored the potential of the heat-shock 
protein co-inducer arimoclomol to ameliorate rhodopsin RP. In a cell model of 
P23H rod opsin RP, arimoclomol reduced P23H rod opsin aggregation and improved 
viability of mutant rhodopsin-expressing cells. In P23H rhodopsin transgenic rat 
models, pharmacological potentiation of the stress response with arimoclomol 
improved electroretinogram responses and prolonged photoreceptor survival, as 
assessed by measuring outer nuclear layer thickness in the retina. Furthermore, 
treated animal retinae showed improved photoreceptor outer segment structure and 
reduced rhodopsin aggregation compared with vehicle-treated controls. The 
heat-shock response (HSR) was activated in P23H retinae, and this was enhanced 
with arimoclomol treatment. Furthermore, the unfolded protein response (UPR), 
which is induced in P23H transgenic rats, was also enhanced in the retinae of 
arimoclomol-treated animals, suggesting that arimoclomol can potentiate the UPR 
as well as the HSR. These data suggest that pharmacological enhancement of 
cellular stress responses may be a potential treatment for rhodopsin RP and that 
arimoclomol could benefit diseases where ER stress is a factor.