Characterizing Corneoscleral Permeability in Microgravity: A Novel Model for Testing Topical Ophthalmic Medication For Spaceflight

Abstract

Purpose : During spaceflight, astronauts may use topical ophthalmic medication for conditions such as inflammation and Spaceflight Associated Neuro-Ocular Syndrome (SANS). We sought to construct a microgravity-proof model for determining corneal permeability, which will be employed on a parabolic flight to test the hypothesis that corneoscleral permeability in microgravity differs from that of terrestrial gravity. The present study seeks to prove the corneoscleral permeability modeling capability of the novel microgravity-proof experimental set-up.

Methods : Corneas were dissected from freshly enucleated bovine eyes and tightly secured in Corning™ Costar™ Netwell™ Inserts (N=6) using rubber gaskets fit to the diameter of the inserts. 3 mL Milli-Q water was pipetted into wells to allow for interfacing with the cornea-insert system. 1 mL 10% fluorescein solution was applied to corneal surfaces and allowed to diffuse into well water. Samples were taken from individual wells at assigned time intervals. Diffusion was characterized by absorption spectroscopy (480 nm). Average sample absorptions were adjusted for absorption of Milli-Q control by subtracting the average control absorption.

Results : Average adjusted sample absorption (AU) and time (min) displayed a strong positive linear correlation (r=0.90, r²=0.82, p=0.013). Interestingly, a lag in diffusion of fluorescein across the corneal membrane resulted in earlier time intervals (0.5 min to 2.5 min) having adjusted absorbances that were essentially 0 AU, causing large standard error (SEM=3377). Nevertheless, the data set highlights that the model can demonstrate relatively low and high concentrations of diffused molecules via absorbance values.

Conclusions : The novel set-up has the capacity to model corneoscleral permeability, demonstrating a successful proof of concept for investigation of permeability variation due to microgravity. Successful trialing with fluorescein indicates that “lag time,” the time it takes before any significant absorbance is measured, must be considered when investigating permeability of ophthalmic medications and constructing time intervals for sampling.

This is a 2021 ARVO Annual Meeting abstract.

 

Figure 1. Absorption of diffused fluorescein at varying time intervals (at 480 nm).

 

Figure 2. Microgravity-proof permeability model. From left: Wells with inserts, insert with fitted gasket, complete model with inserts, gaskets, corneas.