Abstract
Purpose :
Previously, we showed that repeated feeding of all-trans-retinoic acid (atRA) in mice caused myopic shifts in refractive error (RE), increased vitreous chamber depth (VCD), and changes in scleral biomechanics. However, atRA’s effect on choroidal and scleral thickness have not been described. Here, we measured these parameters and tested the dosing effect of atRA. We report RE and optical biometry measurements for all doses. Due to atRA’s potent signaling roles, we also evaluated potential pathological effects on mice through histology and gross necropsy.
Methods :
Male and female C57BL/6J mice were fed sugar pellets containing either high (2.5mg/g, n=5), medium (1mg/g, n=5), low (0.8mg/g, n=5), or control (0mg/g, n=4) levels of atRA daily starting at P30 and ending at P44. Baseline (P30), week 1 (P37), and week 2 (P44) RE, corneal curvature, and spectral domain optical coherence tomography (SD-OCT; Leica, Envisu R4310) measurements were taken. Biometry measurements included axial length (AL), corneal thickness (CT), anterior chamber depth, lens thickness, VCD, retinal thickness (RT), choroidal thickness (ChT), and scleral thickness (ST). After 2 weeks of feeding, eyes and livers were collected for histological analysis and a gross necropsy was performed using hematoxylin and eosin staining. One-way ANOVA with multiple comparisons was used to compare atRA-fed groups to control at the 2-week time point. Correlations were determined by Spearman’s rank correlation test (n=11).
Results :
We observed significant associations between shifts (week 2-baseline) in RT (r(9)=0.6636, p=0.03) and ST (r(9)=-0.7182, p=0.02) on shifts in RE, yet no significant association between shifts in ChT on shifts in RE. atRA feeding did not affect RT, ST, ChT, or AL at 2 weeks. At this time, the only biometric parameter that showed a significant effect of atRA dose was VCD, with the highest dose having a deeper vitreous chamber than control mice (p=0.003). Histology did not reveal remarkable pathology.
Conclusions :
Changes in ChT are often associated with myopic progression. However, here we show that atRA-induced myopic status did not associate with ChT. Elongation of VCD at the highest atRA dose is consistent with previous reports. Further, our data suggest that it is unlikely that myopic changes occur because of systemic or ocular pathology in these atRA doses. Future studies will examine scleral biomechanics across atRA dose.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.