International Journal of Molecular Sciences (Sep 21, 2025) Progressive Ocular Axial Elongation and Retinal Ganglion Cell Degeneration in Mice with Elastic Fiber Disorder

Insignares S, Kuchtey J, Kuchtey RW

DOI: 10.3390/ijms26189221 >>

C57BL/6J Loxl1−/− mice showed enlarged optic nerves, progressive axial globe elongation, and age‑dependent retinal ganglion cell dysfunction, evidenced by reduced pSTR amplitudes and increased latencies, despite normal IOP and preserved visual acuity (quantified by Striatech’s OptoDrum). Axial length increase correlated with RGC functional loss, supporting a mechanistic link between axial myopia and glaucomatous neurodegeneration in elastic fiber disorders.

We previously reported ocular phenotypes of 1-year-old 129S1/SvlmJ lysyl oxidase-like 1 null (Loxl1^-/-) mice. Here we sought to characterize age-dependent changes in C57BL/6J Loxl1^-/- mice in a longitudinal fashion. Retinal ganglion cell (RGC) function was assessed by electroretinography (ERG), and optic nerves were evaluated by histological analysis. Ocular biometric measurements were obtained by optical coherence tomography (OCT). We detected reduced RGC function, revealed by decreased amplitude and increased latency of ERG positive scotopic threshold responses (pSTRs) in Loxl1^-/- mice compared to age-matched wt mice. In addition, there is significant inter-eye asymmetry of RGC function, as well as age-related RGC function loss observed only in Loxl1^-/- mice. Histologically, we observed enlarged optic nerve areas in Loxl1^-/- mice compared to wt mice. Significant ocular biometric differences between two groups were detected, most notably, age-related axial elongation of the globe, accompanied by deepening of anterior chamber depth (ACD). Though eyes elongate with age in both groups, this is more pronounced in Loxl1^-/- mice, and the elongation of the globe correlated with decreased RGC function. The correlation of age-related reduction in RGC function with globe axial elongation may have implications for the association of axial myopia with glaucoma and aging in humans.