Retinal Neuroprotection: Overcoming the Translational Roadblocks.

PURPOSE: To elucidate the issues that have prevented successful translation of neuroprotective therapeutic modalities for retinal disease from the preclinical to the clinical realm and to suggest strategies to circumvent these barriers in order to develop novel treatments to prevent vision loss.

DESIGN

Interpretive essay.

METHODS

Review and synthesis of selected reports of neuroprotective approaches for retinal disease, with interpretation and perspective.

RESULTS

Retinal neuroprotection is defined as any measure that reduces the death of retinal cells or axonal extensions into the optic nerve, and there is a great unmet need for such therapeutic modalities. Despite encouraging preclinical data, the translation of neuroprotective therapies to the clinic has been fraught with failure. Fundamental issues that have plagued this transition include the animal models used in preclinical studies, the reproducibility of the preclinical data, and the choice of meaningful clinical trial endpoints. Developing animal models that more aptly mimic human disease, defining a set of guidelines for preclinical evaluation of neuroprotective therapies in retinal disease, and identifying and validating biomarkers as surrogate clinical endpoints that shorten and optimize drug development timelines may circumvent some of these barriers to translation.

CONCLUSIONS

Neuroprotective therapeutic approaches have the potential to prevent vision loss in millions of people affected with eye diseases worldwide. However, a stigma currently accompanies the concept of neuroprotection because of the many past failures to bridge the gap between the preclinical and clinical realms. Understanding and addressing the fundamental reasons for the failure of translatable research provides hope for the future development of neuroprotective therapies.