Abstract
Purpose :
Interleukin 6 (IL-6) is a pro-inflammatory cytokine whose levels increase in many models of retinal degeneration. We thus hypothesized that IL-6 deficiency would mitigate function loss in light-induced retinal degeneration (LIRD). We have previously shown that IL-6 expression is induced in RPE in response to toxic light exposure.
Methods :
IL-6 knockout (ko) mice were obtained from Jackson Laboratories and bred onto the C57BL/6J Rpe65L450/L450 background (this strain with this allele is more sensitive to LIRD than mice with the M450 allele, which is found in most research strains). Male and female IL6ko/ko RPE65L450/L450 mice and age-matched wild type (wt) C57BL/6J Rpe65L450/L450 were evenly distributed into bright or dim light exposure groups for a total of 6 to 8 mice per group. Mice were dark-adapted overnight. The following morning mice were given 1% Atropine eye drops and 30 minutes later exposed to dim (50 lux) or bright white (40,000 lux) light for 4 hours. Scotopic electroretinograms (ERGs) were performed one week later to assess retina function. ERG data were analyzed using two-way ANOVA with Tukey’s Multiple Comparisons test for mean a- and b-wave amplitudes and two-way ANOVA with Šídák's multiple comparisons test for c-waves.
Results :
Diminution of a-, b-, and c-wave amplitudes were seen in both IL-6 ko and wt mice following LIRD, however, significantly less diminution was seen in the IL-6 ko mice compared to wt. a-, b-, and c-wave amplitudes decreased 59%, 46%, and 56% respectively in wt+bright mice compared to wt+dim, but only 33%, 17%, and 0.8% respectively in ko+bright mice compared to ko+dim. There was no statistical difference between wt+dim and ko+dim groups.
Have we done the ONL counts?
Conclusions :
Deficiency of IL-6 partially but significantly protected against loss of function in photoreceptor cells, inner retina neurons, and RPE cells in a LIRD model. These results suggest that IL-6 is part of an inflammatory process that in part underlies the retinal degeneration observed after exposure of mice to toxic levels of light.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.