Researchers at the University of Pennsylvania developed the in vitro model of the blinking human eye and described it in Nature Medicine. The researchers think the model can overcome limitations of the current preclinical screening tools available to developers of molecules designed to treat dry-eye disease through the modification of the underlying biomechanics of the condition.
The authors wrote, “Investigating this promising therapeutic approach ... remains a challenge due to the limitations of current in vitro platforms that largely fail to capture the dynamic environmental features of the ocular surface. While laboratory animals provide alternatives, the well-documented interspecies differences in the dynamics of blinking and the tear film make this strategy problematic.”
To improve on these options, the researchers grew human eye cells on a contact lens-shaped scaffold and used a slab of gelatin to mimic the eyelid. The gelatin slides over the eye-on-a-chip at the same rate as the human eye blinks.
This model was modified to mimic dry-eye disease, a condition that results from tears spread over the eye during blinking evaporating faster than they are replenished. The resulting drying out of the eye leads to inflammation and irritation.
The researchers halved the blinking rate and otherwise modified the model to mimic the eye disease before using it to study lubricin, a mucin-like glycoprotein that Dompé Farmaceutici has trialled in humans with dry-eye disease.
Applying lubricin reduced the friction generated as the eyelid moved over the eye-on-a-chip to a greater extent than was achieved using saline or artificial tears. After three days, the ocular surface of the model treated with lubricin appeared intact, whereas damage was evident in the control arm.
The results are in keeping with clinical data on the effects of lubricin, increasing the confidence of the researchers in the accuracy of the model.
In another study, the researchers sought to move understanding of the effects of lubricin beyond what was found in the clinical trials. To do so, the researchers assessed whether lubricin modulates ocular inflammatory signaling pathways, leading to evidence of the drug’s effect on the expression of toll-like receptor-4.
Buoyed by the findings, the researchers expressed hopes that the model will be used in drug screening and other applications. However, they also acknowledged the limitations of the model.
The authors wrote, “Our model still shows significant differences from its in vivo counterpart. For example, our system fails to reconstitute the vascularity and the immune cell components in the conjunctiva, which is particularly important for modeling immune responses in complex ocular diseases such as dry eye.”