Abstract
Purpose :
Obstruction of normal vision early in development can produce a severe vision impairment called amblyopia. Treatment typically involves patching the dominant eye. Difficulty with treatment compliance and amblyopia recurrence can lead to more patching later in development. Children with a history of patching exhibit less recovery with later patching compared to children that were never patched, raising the possibility that the initial treatment reduces plasticity and attenuates recovery potential. Our objective was to assess whether an early and brief monocular deprivation (MD) reduced the impact of a subsequent period of MD later in development.
Methods :
We examined two markers of MD-induced plasticity in the lateral geniculate nucleus (LGN), namely, the reduction of neuron soma size and loss of neurofilament. Two animal groups were examined. The prior MD group received 1 week of MD at the critical period peak followed by binocular vision before receiving a later MD for 10 days, this time of the fellow eye. Our comparison group received only the later MD for 10 days. Tissue sections containing the LGN were stained for Nissl substance, or were immunolabeled for neurofilament. Soma size reduction was assessed from Nissl sections using the nucleator stereology probe, and loss of neurofilament was measured using QuPath software.
Results :
Animals subjected to the prior MD condition exhibited a 7% reduction of deprived-eye neuron size. Age-matched animals that received only the later MD showed a 15% reduction of soma size, which was a significantly larger effect (p=0.03). Likewise, animals subjected to a prior MD showed a smaller loss of neurofilament (26%) compared to animals that did not have a prior MD (55%), which was a significant difference (p=0.0007).
Conclusions :
Our results are consistent with the hypothesis that early MD reduces plasticity capacity in the LGN. This raises the intriguing possibility that poor recovery outcomes in patients with a history of prior treatment derives from a reduction of plasticity potential produced by the treatment itself. The plasticity-inhibiting characteristics of neurofilament raise the possibility that the smaller effect on soma size observed in our prior MD group may in part originate from the lack of cytoskeletal malleability that acts as a molecular brake on plasticity.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.