Retinal dysfunction and visual impairment in aged Aldh1a1 knockout mice

Abstract

Purpose : We have shown that the Aldh1a1 knockout (Aldh1a1^-/-) mice exhibited dorsal choroidal hypoplasia, but no degeneration was observed in photoreceptors and RPE in the younger age (So Goto et al., Elife 2018). We then found that aged (over 18-month-old) Aldh1a1^-/- mice showed degeneration both in photoreceptors and RPE (ARVO 2017: Program Number: 3379). Here we demonstrate the progression of the degeneration by measuring retinal morphological properties and visual functions among the middle-aged (10-month-old), the aged Aldh1a1^-/- mice and the age-matched control (WT) mice.

Methods : For morphological characterization, flat mount immunohistochemical analysis of RPE was performed with ZO-1 antibodies. Electron microscope analysis was performed in vertical sections of the posterior eyes. Focal electroretinogram with Micron IV (Phoenix Research) was performed for the electrophysiological examination. Optomotor response was examined by the qOMR system (PhenoSys).

Results : RPE-size in middle-aged Aldh1a1^-/- mice was not significantly different from that of WT mice, but RPE-size in aged Aldh1a1^-/- mice was significantly larger than that of WT mice. Electron micrographs of middle-aged Aldh1a1^-/- eyes showed only disorganized basal infoldings, whereas that of aged Aldh1a1^-/- eyes showed the disorganized basal infoldings, vacuoles and the disturbance of photoreceptor layers between outer and inner segments. Dark-adapted b-wave amplitude in middle-aged Aldh1a1^-/- mice was significantly decreased at one of the eight tested flash intensity, whereas that in aged Aldh1a1^-/- mice was significantly decreased at six of the eight tested flash intensity. Spatial contrast sensitivity function (CSF) was not significantly different between middle-aged Aldh1a1^-/- and WT mice. On the other hand, CSF was significantly reduced in aged Aldh1a1^-/- mice compared with WT mice.

Conclusions : The onset of the RPE degeneration was observed in the middle-aged Aldh1a1^-/- mice. However, the retinal function and visual acuity were relatively conserved. The aged Aldh1a1^-/- mice showed the dysfunction of the retina and visual impairment.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.