The Translational Value of Preclinical Research: Lessons from More Than Forty Years of Retinal Research
- 1Department of Biology, University of Pisa, 56127 Pisa, Italy
Abstract
The present paper is based on a long personal experience of research on the retina. Over almost forty years, questions that were originally pursued as curiosity-driven physiology progressively acquired unexpected translational implications. The retina provides a particularly instructive setting in which to examine translational potential because its accessible and highly organized neural and vascular architecture has allowed mechanisms identified in experimental models to be tested as potential therapeutic targets. Three research trajectories from our laboratory are discussed as examples of different translational outcomes. Studies of the somatostatinergic system illustrate how a strong mechanistic rationale and convincing preclinical efficacy may not necessarily translate into comparable clinical benefit. Investigations of the uPA/uPAR system and its pharmacological inhibition show how a candidate that does not reach clinical application may nevertheless provide durable insight into disease mechanisms and identify biologically relevant pathways. Conversely, studies of β-adrenoceptor signaling and propranolol in retinopathy of prematurity illustrate how drug repurposing can shorten the distance between experimental evidence and clinical investigation, while still leaving important questions about dose, safety, and delivery. These experiences also highlight model selection, disease stage, pharmacokinetics, tissue exposure, reproducibility and patient heterogeneity as critical determinants of translational success. Taken together, my experience of research on the retina suggests that translation should be viewed not as a one-way progression from bench to bedside, but as an iterative process in which experimental findings, clinical outcomes and even unsuccessful therapeutic attempts continuously reshape biological questions.
Related
- Taming inflammation in coronary artery disease: lessons learned, translational breakthroughs, and future directions
- Preclinical mouse models of multiple myeloma: a clinically oriented guide to model selection, validation, and translational application
- Micronized Bone Marrow and Niche Preservation: Biological Rationale, Preclinical Evidence, Translational Potential and Limitations
- Phage therapy for multidrug-resistant Serratia marcescens infection: mechanisms, preclinical evidence, and translational challenges
- Characterization of the knock-in AppSAA mouse model as a powerful tool for Alzheimer's disease preclinical research.
BibTeX
@article{bagnoli2026translational,
title = {{The Translational Value of Preclinical Research: Lessons from More Than Forty Years of Retinal Research}},
author = {Paola Bagnoli},
journal = {Biomedicines},
year = {2026},
month = oct,
doi = {10.3390/biomedicines14102405},
url = {https://europepmc.org/article/PMC/PMC13701875},
note = {CC BY},
}
RIS
TY - JOUR
TI - The Translational Value of Preclinical Research: Lessons from More Than Forty Years of Retinal Research
AU - Paola Bagnoli
PY - 2026
DA - 2026/10/01
JO - Biomedicines
DO - 10.3390/biomedicines14102405
UR - https://europepmc.org/article/PMC/PMC13701875
AB - The present paper is based on a long personal experience of research on the retina. Over almost forty years, questions that were originally pursued as curiosity-driven physiology progressively acquired unexpected translational implications. The retina provides a particularly instructive setting in which to examine translational potential because its accessible and highly organized neural and vascular architecture has allowed mechanisms identified in experimental models to be tested as potential therapeutic targets. Three research trajectories from our laboratory are discussed as examples of different translational outcomes. Studies of the somatostatinergic system illustrate how a strong mechanistic rationale and convincing preclinical efficacy may not necessarily translate into comparable clinical benefit. Investigations of the uPA/uPAR system and its pharmacological inhibition show how a candidate that does not reach clinical application may nevertheless provide durable insight into disease mechanisms and identify biologically relevant pathways. Conversely, studies of β-adrenoceptor signaling and propranolol in retinopathy of prematurity illustrate how drug repurposing can shorten the distance between experimental evidence and clinical investigation, while still leaving important questions about dose, safety, and delivery. These experiences also highlight model selection, disease stage, pharmacokinetics, tissue exposure, reproducibility and patient heterogeneity as critical determinants of translational success. Taken together, my experience of research on the retina suggests that translation should be viewed not as a one-way progression from bench to bedside, but as an iterative process in which experimental findings, clinical outcomes and even unsuccessful therapeutic attempts continuously reshape biological questions.
SN - 2227-9059
ER -