Defocused Image Changes Signaling of Ganglion Cells in the Mouse Retina

Abstract

Myopia is a substantial public health problem worldwide. Although it is known that defocused images alter eye growth and refraction, their effects on retinal ganglion cell (RGC) signaling that lead to either emmetropization or refractive errors have remained elusive. This study aimed to determine if defocused images had an effect on signaling of RGCs in the mouse retina. ON and OFF alpha RGCs and ON–OFF RGCs were recorded from adult C57BL/6J wild-type mice. A mono green organic light-emitting display presented images generated by PsychoPy. The defocused images were projected on the retina under a microscope. Dark-adapted mouse RGCs were recorded under different powers of projected defocused images on the retina. Compared with focused images, defocused images showed a significantly decreased probability of spikes. More than half of OFF transient RGCs and ON sustained RGCs showed disparity in responses to the magnitude of plus and minus optical defocus (although remained RGCs we tested exhibited similar response to both types of defocus). ON and OFF units of ON–OFF RGCs also responded differently in the probability of spikes to defocused images and spatial frequency images. After application of a gap junction blocker, the probability of spikes of RGCs decreased with the presence of optical defocused image. At the same time, the RGCs also showed increased background noise. Therefore, defocused images changed the signaling of some ON and OFF alpha RGCs and ON–OFF RGCs in the mouse retina. The process may be the first step in the induction of myopia development. It appears that gap junctions also play a key role in this process.

Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina

“…It has been proposed that retinal signals mediated the eye's refractive development via a retina-to-sclera signaling pathway [47,48]. This study in combination with our previous research [19] showed that defocused images change mouse RGC signaling which might serve as the primary initiators of this retina-to-sclera signaling mechanism.…”

“…Compared with focused images, defocused images will change the size, focused plane and light intensity. Even though these changes are tiny, the changes will be important for retina to discern the defocused image [19]. The question is whether the RGCs can sense it and code the information into spikes and then send it to the brain.…”

“…This was achieved by holding the membrane potential (V h ) on the levels matching either the excitatory (V h = −68 mV) or the inhibitory reversal potentials (V h = 0 mV). First, we carried out measurements when focused images were projected and then switched to optical defocused image (± 20 dioptric powers) counterparts (light stimuli were 0.002 cycles/degree gratings, light intensity = 5.09 × 10 4 Rh*/rod/sec) under a 40× water immersion lens by using a custom-made image projection system as described before [19]. However, this data should be interpreted with caution, as defocusing under microscopy can change the light intensities and receptive field of RGCs.…”

“…However, this data should be interpreted with caution, as defocusing under microscopy can change the light intensities and receptive field of RGCs. The receptive field can be kept consistent by programing the projected image area, and the light intensities can be varied but it may not change the whole cell responses [19].…”

“…It has been suggested that subsets of retinal ganglion cells (RGCs) respond to focused/defocused images and thus may play pivotal roles in modulating growth and refraction and, hence, myopia development in the retina [19]. As studies have demonstrated that the retina detects signs of defocus during the visually guided refractive development period [20], retinal signaling is a strong candidate for mediating the retina to sclera signaling pathway in refractive development [21,22], ultimately leading to myopia.…”