The persistent impairment of the cone pathway after oxygen-induced retinopathy in mice

Abstract

Purpose : Premature babies with retinopathy of prematurity (ROP) still suffer from visual impairment even if ROP resolves; however, the underlying mechanisms of post-ROP visual problems are unclear. Using a mouse model with oxygen-induced retinopathy (OIR), it has been demonstrated that the rod and cone pathways are impaired during the neovascularization stage (Vessey et al, 2011) and the impaired rod pathway is fully recovered 4 weeks after OIR (Nakamura et al, 2012). Here we sought to determine the extent to which the cone pathway remains impaired after OIR.

Methods : Pups were treated with 75% oxygen from postnatal 7 (P7) to P12 to induce retinopathy. Since the regression of neovascularization was completed at P25, OIR mice older than P60 and age-matched controls were used for transretinal (ex vivo) electroretinogram (ERG) and in vivo pattern ERG (PERG) recordings. Light-adapted transretinal ERGs exhibited b- and d-waves that reflect activity of ON and OFF cone bipolar cells, respectively. The a-waves were isolated by pharmacologically blocking b- and d-waves. PERGs exhibited an early positive (P1) and later negative (N2) component, which reflect the function of retinal ganglion cells in light-adapted conditions.

Results : The peak amplitudes of light-adapted a-, b-, and d-waves of transretinal ERGs obtained from P90 to P100 OIR mice (n=12) were reduced to some degree at all tested light intensities compared to those obtained from control mice (n=8). However, only the changes occurring in b-waves were significant (P<0.05; t-test). In addition, PERG results showed that both P1 and P1-N2 wave amplitudes decreased by 45% and 44%, respectively, for P60 OIR mice (n=4) compared to control mice (n=6) at a mean luminance of 50 cd/m². When the mean luminance was increased to 100 cd/m², a similar degree of suppression of P1 and P1-N2 waveforms remained in OIR mice.

Conclusions : The results suggest that the ON cone pathway is impaired to a greater extent than the OFF cone pathway at a level of bipolar cells after OIR. This different effect on ON and OFF bipolar cells may result in the impairment of functional integrity of retinal ganglion cells revealed by PERGs. Knowledge gained from the results helps to understand the mechanisms by which premature infants suffer from visual problems after ROP.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.