Pharmacological approaches to retinitis pigmentosa: A laboratory perspective

Abstract

Retinal photoreceptors are highly specialized and performing neurons. Their cellular architecture is exquisitely designed to host a high concentration of molecules involved in light capture, phototransduction, electric and chemical signaling, membrane and molecular turnover, light and dark adaption, network activities etc. Such high efficiency and molecular complexity require a great metabolic demand, altogether conferring to photoreceptors particular susceptibility to external and internal insults, whose occurrence usually precipitate into degeneration of these cells and blindness. In Retinitis Pigmentosa, an impressive number of mutations in genes expressed in the retina and coding for a large varieties of proteins leads to the progressive death of photoreceptors and blindness. Recent advances in molecular tools have greatly facilitated the identification of the underlying genetics and molecular bases of RP leading to the successful implementation of gene therapy for some types of mutations, with visual restoration in human patients. Yet, genetic heterogeneity of RP makes mutation-independent approaches highly desirable, although many obstacles pave the way to general strategies for treating this complex disease, which remains orphan. The review will focus on treatments for RP based on pharmacological tools, choosing, among the many ongoing studies, approaches which rely on strong experimental evidence or rationale. For perspective treatments, new concepts are foreseen to emerge from basic studies elucidating the pathways connecting the primary mutations to photoreceptor death, possibly revealing common molecular targets for drug intervention.

Keywords: Apoptosis; Ceramide; Environmental enrichment; Inflammation; Microglia; Neurotrophic factors; Orphan disease; Photoreceptors; Rare disease.