Myopia-related changes to retinal astrocytes and associated retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) of juvenile marmosets

Abstract

Purpose : Retinal astrocytes are key elements of neuronal support. We hypothesize that the mechanical elongation of the globe due to myopia progression affects astrocytes and predisposes the myopic eye to ocular complications. In this study, we characterized the effect of lens-induced myopia on retinal astrocyte coverage and distribution in relationship to RNFL and GCL thickness of common marmosets (Callithrix Jacchus).

Methods : Eight myopic and ten control (myopic average Rx: -5.49±2.48D, age: 195±16.75 days; controls average Rx: -1.10±0.62D, age: 293±90.56 days, p<0.01) marmoset retinal whole mounts were labeled with anti-GFAP and anti-Sox9 to visualize astrocytes within the superficial layer. Astrocyte numbers, RNFL and GCL thickness were quantified at the parafoveal, peripapillary, and peripheral retinal regions using confocal microscopy and optical coherence tomography (OCT). Ocular magnification was corrected using Kang’s method. Statistical analysis was performed using Mann-Whitney U non-parametric testing at a confidence level of 95%.

Results : Myopes had less astrocytes (controls 248.55±18.55, myopes 154.96±23.3, p<0.05), thinner RNFL (controls 33.80 mm ±12.4; myopes 24.57 mm ±3.3, p<0.01) and thinner GCL (controls 23.38 mm ±2.9; myopes mm 21.52±2.9, p=0.02) in the parafovea compared to controls. In control eyes, the number of astrocytes increased as the overall GCL (R²=0.19, p<0.01) and peripapillary RNFL (R²=0.81, p<0.04) thickened; while in myopic eyes, these were not significant. In control eyes, the RNFL thickened as eyes grew normally (superior and nasal peripapillary R²=0.80, p<0.02; R²=0.86, p=0.02; temporal parafovea R²=0.79, p<0.05; temporal periphery R²=0.97, p<0.02). In myopic eyes, on the opposite, the GCL thinned as eyes grew larger and developed myopia in the superior periphery (R²=0.86, p<0.01).

Conclusions : Untreated marmosets exhibit a thickening of the RNFL as their eyes grew normally and this was accompanied by an increase in the astrocyte bodies observed. Myopic marmosets, however, exhibited lower astrocyte numbers, their RNFL and GCL thinned as eyes grew myopic. These results suggest compromised glial structure and function, leading to inadequate ability to regulate local ions and support neural tissue in eyes with progressing myopia.

This is a 2021 ARVO Annual Meeting abstract.