Abstract
Purpose :
Evidence from our lab and others suggests that myopic eyes experience thickness alterations in the inner retina that differ from non-myopic eyes. The purpose of this study is to characterize the ganglion cell complex at the cellular and functional levels in marmosets with induced myopia
Methods :
Juvenile marmosets (Callithrix jacchus, N=14) were treated binocularly with negative soft contact lens for 22 weeks to induce myopia compared to untreated age-matched controls (N=11). Cycloplegic refraction (Rx), vitreous chamber depth (VCD), peripapillary retinal nerve fiber layer thickness (ppRNFL) and full field photopic negative response (PhNR) were measured prior to immunostaining. Retinal wholemounts were labeled for Brn3a, Sox9 and GFAP to visualize retinal ganglion cells (RGC), astrocyte soma and cytoskeleton, respectively. The spatial distribution of RGCs, astrocytes and GFAP expression was quantified at the retina peripapillary (pp), mid-periphery (mph) and periphery (ph) and corrected for myopic magnification
Results :
Treated marmosets (Tx) developed axial myopia (Rx:-7.31±1.14D, VCD: 7.06±0.09mm) compared to controls (C; Rx:-1.40±0.17D, VCD: 6.71±0.04mm, p<0.01), had a thinner ppRNFL (Tx: 31.82±5.82μm, C: 40.98±7.29μm, p<0.05), reduced Brn3a+ RGC (Tx: 10668±613, C: 13417±917cells/mm2, p<0.05) and Sox9+ astrocyte density in the peripapillary retina (Tx: 2415±315, C: 4173±340cells/mm2, p<0.01). Greater myopia was associated with lower RGC and astrocyte densities in the peripapillary (RGC: R2=0.70, p<0.05; astrocytes: R2=0.56, p<0.05). Despite the reduced astrocyte numbers in treated marmosets, their GFAP expression was greater relative to controls in all retinal regions (pp: +29.84%, mph: +41.28%, ph: +68.40%) and increased with greater degrees of myopia and axial elongation. A trend towards higher PhNR saturated amplitudes as Brn3a+ RGC counts increased was observed (R2=0.65; p=0.19). Astrocyte morphometric measures and ppRNFL did not show a significant relationship with PhNR
Conclusions :
Myopic retinas without any retinal pathology exhibit thinner RNFL, reduced ganglion cell and astrocyte numbers in the peripapillary retina, along with a global increase in GFAP expression that can be partially explained by myopic growth. Whether these early structural and cellular changes might be adaptive or reactive and serve as cellular biomarkers of myopia-related pathologies remains to be investigated
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.