Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease

Cross-modal prediction in speech depends on prior linguistic experience

The sight of a speaker’s facial movements during the perception of a spoken message can benefit speech processing through online predictive mechanisms. Recent evidence suggests that these predictive mechanisms can operate across sensory modalities, that is, vision and audition. However, to date, behavioral and electrophysiological demonstrations of cross-modal prediction in speech have considered only the speaker’s native language. Here, we address a question of current debate, namely whether the level of representation involved in cross-modal prediction is phonological or pre-phonological. We do this by testing participants in an unfamiliar language. If cross-modal prediction is predominantly based on phonological representations tuned to the phonemic categories of the native language of the listener, then it should be more effective in the listener’s native language than in an unfamiliar one. We tested Spanish and English native speakers in an audiovisual matching paradigm that allowed us to evaluate visual-to-auditory prediction, using sentences in the participant’s native language and in an unfamiliar language. The benefits of cross-modal prediction were only seen in the native language, regardless of the particular language or participant’s linguistic background. This pattern of results implies that cross-modal visual-to-auditory prediction during speech processing makes strong use of phonological representations, rather than low-level spatiotemporal correlations across facial movements and sounds