Using Virtual Patients to Predict Perceptual Outcomes for Optogenetic Sight Recovery Technologies

Area of Science:

• Biomedical Engineering
• Neuroscience
• Ophthalmology

Background:

• Optogenetics is a promising strategy for vision restoration in inherited retinal diseases.
• Current clinical trials use light-sensitive proteins (opsins) to restore light responsiveness in retinal cells.
• Predicting patient perceptual outcomes from ex vivo opsin activity remains a challenge.

Purpose of the Study:

• To introduce a virtual patient framework linking opsin properties to perceptual outcomes.
• To predict temporal contrast sensitivity functions from microbial opsin photocurrent responses.
• To provide a tool for selecting effective opsins for clinical translation.

Main Methods:

• Developed a computational framework simulating optogenetically evoked neural activity.
• Quantitatively linked opsin sensitivity and kinetics to predicted patient visual performance.
• Used the framework to predict temporal contrast sensitivity functions from opsin photocurrent data.

Main Results:

• Opsin sensitivity and kinetics were shown to jointly determine perceptual outcomes.
• Simulations indicated that increased sensitivity can impair temporal resolution, affecting perception of fast stimuli.
• The virtual patient framework successfully predicted temporal contrast sensitivity from opsin responses.

Conclusions:

• The virtual patient framework enables quantitative prediction of perceptual outcomes from opsin characteristics.
• This computational tool can guide the selection and optimization of opsins for vision restoration therapies.
• The framework facilitates the development of next-generation sight restoration strategies.