title: 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.
authors.affiliation: Neuroscience Institute, Italian National Research Council (CNR), Area della Ricerca, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Guadagni
authors.affiliation: Neuroscience Institute, Italian National Research Council (CNR), Area della Ricerca, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Novelli
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Piano
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gargini
authors.affiliation: Neuroscience Institute, Italian National Research Council (CNR), Area della Ricerca, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy. Electronic address: enrica.strettoi@in.cnr.it.
authors.forename: Enrica
authors.initials: E
authors.lastname: Strettoi
mesh_terms: D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012174:Retinitis Pigmentosa / Q000188:drug therapy*; D013879:Thioredoxins / Q000627:therapeutic use
chemical_list: D020934:Ciliary Neurotrophic Factor; C488098:NXNL1 protein, human; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D013879:Thioredoxins
keywords: Apoptosis; Ceramide; Environmental enrichment; Inflammation; Microglia; Neurotrophic factors; Orphan disease; Photoreceptors; Rare disease