From retinal development to drug development
Enrique de la Rosa
CIB / CSIC (Madrid, Spain)
Our studies in retinal development allowed for the characterization of several phases of programmed cell death in the chick and mouse developing retina, as well as of its regulation. Among many other factors, proinsulin, the molecular precursor of insulin, resulted to be a potent antiapoptotic factor during development, capable of activating several cell survival pathways and, thus, we decided to study its possible translation to human therapy. Proinsulin delays photoreceptor cell death in a mouse model of Retinitis Pigmentosa and prolongs visual function. The spin-off created by our group, ProRetina Therapeutics SL, worked on the development of a possible neuroprotective therapy applicable in clinic.
Besides that, we have employed neuroprotection as a tool to characterize the physiopathological mechanisms of retinal degeneration in order to provide novel therapeutic targets, which will allow performing additional proofs of concept of potential drugs. We have shown that reactive gliosis of the Müller cells and astrocytes, together with resident microglia activation and infiltration of macrophages in the retina, are disease-associated processes that reflect a significant inflammatory response, concurrent with the degeneration. We intend to attenuate the degenerative process and the loss of photoreceptors through the development of therapies targeting early molecular and cellular alterations, common to different types of Retinitis Pigmentosa, regardless of the type of the underlying mutation. Thereby, a potential therapy could be developed, that were useful for a large number of patients and able to prolong their visual function for longer time.